Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Rheumatoid Arthritis Study in Participants on a Background Treatment of Methotrexate (FLEX M)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01198002
Recruitment Status : Terminated (Terminated not based on safety concerns, but due to insufficient efficacy.)
First Posted : September 9, 2010
Results First Posted : May 8, 2018
Last Update Posted : May 8, 2018
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Drug: LY2127399
Drug: Placebo Q2W
Drug: Placebo Q4W
Drug: Methotrexate
Enrollment 1041
Recruitment Details  
Pre-assignment Details Study had a blinded Treatment Period 1 (Weeks 0-52), a non-blinded Treatment Period 2 (Weeks 52-100) and a post-treatment follow-up (24-48 weeks in length). All participants were assessed for nonresponse at Week 16 with non-responders (NR) defined as participants with <20% improvement from baseline in both tender and swollen joint counts.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description

Treatment Period 1 (Weeks 0-52): A loading dose of 240 milligrams (mg) (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered subcutaneously (SC) every 4 weeks (Q4W). For blinding purposes, participants alternated injections of LY2127399 and injections of placebo every 2 weeks (Q2W).

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

At Week 16, NR received a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Period Title: Treatment Period 1 (Weeks 0-52)
Started 345 347 349
Received at Least 1 Dose of Study Drug 345 345 348
Week 16 NR 58 62 90
Post-Treatment Follow-Up Population 293 303 307
Completed 70 [1] 73 [1] 80 [1]
Not Completed 275 274 269
Reason Not Completed
Adverse Event             18             11             11
Death             2             0             1
Lack of Efficacy             10             9             6
Entry Criteria Not Met             1             3             3
Lost to Follow-up             0             2             0
Withdrawal by Subject             16             21             12
Physician Decision             1             2             2
Protocol Violation             14             10             10
Sponsor Decision             213             216             224
[1]
Those who completed 52-week Treatment Period 1 including both Week 16 responders and NR.
Period Title: Treatment Period 2 (Weeks 52-100)
Started 70 73 80
Completed 1 0 2
Not Completed 69 73 78
Reason Not Completed
Adverse Event             2             0             1
Lack of Efficacy             3             1             1
Entry Criteria Not Met             1             0             0
Lost to Follow-up             0             2             0
Physician Decision             1             0             1
Sponsor Decision             62             70             75
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo Total
Hide Arm/Group Description

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

At Week 16, NR received a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Total of all reporting groups
Overall Number of Baseline Participants 345 347 349 1041
Hide Baseline Analysis Population Description
All randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 345 participants 347 participants 349 participants 1041 participants
53.7  (11.8) 52.8  (10.9) 52.9  (11.5) 53.2  (11.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 345 participants 347 participants 349 participants 1041 participants
Female
294
  85.2%
291
  83.9%
292
  83.7%
877
  84.2%
Male
51
  14.8%
56
  16.1%
57
  16.3%
164
  15.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 345 participants 347 participants 349 participants 1041 participants
Hispanic or Latino
63
  18.3%
67
  19.3%
61
  17.5%
191
  18.3%
Not Hispanic or Latino
140
  40.6%
131
  37.8%
140
  40.1%
411
  39.5%
Unknown or Not Reported
142
  41.2%
149
  42.9%
148
  42.4%
439
  42.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 345 participants 347 participants 349 participants 1041 participants
American Indian or Alaska Native
20
   5.8%
18
   5.2%
15
   4.3%
53
   5.1%
Asian
100
  29.0%
102
  29.4%
101
  28.9%
303
  29.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   0.3%
0
   0.0%
1
   0.1%
Black or African American
22
   6.4%
19
   5.5%
22
   6.3%
63
   6.1%
White
191
  55.4%
197
  56.8%
200
  57.3%
588
  56.5%
More than one race
9
   2.6%
7
   2.0%
7
   2.0%
23
   2.2%
Unknown or Not Reported
3
   0.9%
3
   0.9%
4
   1.1%
10
   1.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 345 participants 347 participants 349 participants 1041 participants
United States
56
  16.2%
55
  15.9%
56
  16.0%
167
  16.0%
Taiwan
10
   2.9%
11
   3.2%
10
   2.9%
31
   3.0%
Slovakia
4
   1.2%
3
   0.9%
4
   1.1%
11
   1.1%
Ukraine
23
   6.7%
22
   6.3%
23
   6.6%
68
   6.5%
Lithuania
6
   1.7%
6
   1.7%
8
   2.3%
20
   1.9%
Russia
23
   6.7%
25
   7.2%
24
   6.9%
72
   6.9%
Colombia
19
   5.5%
21
   6.1%
11
   3.2%
51
   4.9%
Sri Lanka
1
   0.3%
2
   0.6%
2
   0.6%
5
   0.5%
India
5
   1.4%
5
   1.4%
4
   1.1%
14
   1.3%
Hungary
8
   2.3%
9
   2.6%
8
   2.3%
25
   2.4%
Mexico
20
   5.8%
16
   4.6%
28
   8.0%
64
   6.1%
Argentina
17
   4.9%
17
   4.9%
16
   4.6%
50
   4.8%
Malaysia
2
   0.6%
3
   0.9%
3
   0.9%
8
   0.8%
Brazil
14
   4.1%
14
   4.0%
13
   3.7%
41
   3.9%
Poland
33
   9.6%
34
   9.8%
33
   9.5%
100
   9.6%
Croatia
1
   0.3%
0
   0.0%
1
   0.3%
2
   0.2%
Romania
0
   0.0%
2
   0.6%
2
   0.6%
4
   0.4%
South Africa
16
   4.6%
16
   4.6%
16
   4.6%
48
   4.6%
Bulgaria
11
   3.2%
11
   3.2%
10
   2.9%
32
   3.1%
Japan
52
  15.1%
53
  15.3%
53
  15.2%
158
  15.2%
New Zealand
1
   0.3%
0
   0.0%
1
   0.3%
2
   0.2%
South Korea
23
   6.7%
22
   6.3%
23
   6.6%
68
   6.5%
1.Primary Outcome
Title Percentage of Participants With American College of Rheumatology 20% Response (ACR20) at Week 24
Hide Description ACR Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis (RA). ACR20 Responder: had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and C-reactive protein (CRP). Percentage of participants achieving ACR20 response=(number of ACR20 responders) / (number of participants treated) * 100. All NR at Week 16 as well as all participants who discontinued study treatment at any time for any reason were defined as NR starting at that time-point and going forward, including Week 24 endpoint.
Time Frame Baseline through 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable ACR20 responder data. If participant's CRP was missing, last post-baseline value was used. If ACR was missing after carrying forward CRP, last post-baseline ACR response was used. Data after Week 16 for Week 16 NR were not included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Overall Number of Participants Analyzed 330 332 335
Measure Type: Number
Unit of Measure: percentage of participants
29.7 32.8 25.1
2.Primary Outcome
Title Change From Baseline to Week 52 in Van Der Heijde Modified Total Sharp Score (mTSS)
Hide Description The mTSS quantifies the extent of bone erosions and joint space narrowing for 44 and 42 joints. X-rays of the hands/wrists and feet are scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (ankylosis or complete dislocation). Erosions scores (range = 0 to 220 for 44 joints) and narrowing scores (range = 0 to 168 for 42 joints) were added to obtain the mTSS (range = 0 [normal] to 388 [maximal disease]). Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with treatment and region as fixed factors and baseline as a covariate.
Time Frame Baseline, 52 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable mTSS data. A linear extrapolation method was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

At Week 16, NR received a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Overall Number of Participants Analyzed 295 304 306
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
1.43  (0.27) 0.84  (0.27) 1.57  (0.27)
3.Primary Outcome
Title Change From Baseline to Week 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI)
Hide Description The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty [0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (severe disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Time Frame Baseline, 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable HAQ-DI data. Modified Baseline Observation Carried Forward (mBOCF) was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Overall Number of Participants Analyzed 329 327 328
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.26  (0.03) -0.30  (0.03) -0.20  (0.03)
4.Secondary Outcome
Title Percentage of Participants With American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response
Hide Description ACR Responder Index: Composite of clinical, laboratory, and functional measures of RA. ACR50 Responder: had ≥50% improvement from baseline in both 68 tender joint (TJ) and 66 swollen joint (SJ) counts and ≥50% improvement in at least 3 of 5 criteria: participant's (Pt's) and physician's global assessment of disease activity, HAQ-DI (measured Pts' perceived degree of difficulty performing daily activities), joint pain, and CRP. Percentage of Pt achieving ACR50 response=(number (No.) of ACR50 responders) / (No. of Pts treated) * 100. ACR70 Responder: had ≥70% improvement from baseline in both TJ and SJ counts and ≥70% improvement in at least 3 of same 5 criteria for ACR50. Percentage of Pts achieving ACR70 response= (No. of ACR70 responders) / (No. of Pts treated) * 100. All NR at Week 16 as well as all Pts who discontinued study treatment at any time for any reason were defined as NR starting at that time-point and going forward, including Weeks 24 and 52 endpoints.
Time Frame Baseline through 24 weeks and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable ACR50 or ACR70 responder data. If participant's CRP was missing, last post-baseline value was used. If ACR was missing after carrying forward CRP, last post-baseline ACR response was used. Data after Week 16 for Week 16 NR were not included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Overall Number of Participants Analyzed 330 332 335
Measure Type: Number
Unit of Measure: percentage of participants
ACR50 - Week 24 10.6 11.1 10.1
ACR50 - Week 52 4.2 3.0 4.8
ACR70 - Week 24 3.9 3.0 3.0
ACR70 - Week 52 1.5 1.2 1.8
5.Secondary Outcome
Title Change From Baseline in Disease Activity Score Based on 28 Joint Count and C-Reactive Protein Level (DAS28-CRP)
Hide Description Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP [milligrams per liter (mg/L)], and participant's global assessment of disease activity using visual analog scale (VAS) (participant global VAS). DAS28-CRP=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.36*natural log(CRP+1)+0.014*participant global VAS+0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity and remission is DAS28-CRP <2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Time Frame Baseline, 24 weeks and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable DAS28-CRP data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Overall Number of Participants Analyzed 328 327 328
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 24 -1.02  (0.07) -1.00  (0.07) -0.78  (0.07)
Week 52 -1.07  (0.07) -1.00  (0.07) -0.80  (0.07)
6.Secondary Outcome
Title Percentage of Participants With DAS28-CRP Based European League Against Rheumatism (EULAR) Response
Hide Description EULAR Responder index based on 28 joint counts categorizes clinical response based on improvement since baseline in DAS28-CRP. DAS28-CRP scores range from 1.0-9.4, where lower scores indicated less disease activity. High disease activity: DAS28-CRP >5.1, low disease activity: DAS28-CRP <3.2, and remission: DAS28-CRP <2.6. Participants are categorized as EULAR responders or NR based on improvement of DAS28-CRP scores from baseline. EULAR DAS28-CRP responder index defines a good (absolute: <3.2 or >1.2 improvement from baseline), moderate (absolute: 3.2-5.1 or 0.6-1.2 improvement from baseline), or no response (absolute: >5.1 or <0.6 improvement from baseline). Percentage of participants with DAS28-CRP based EULAR response =(number of participants with specific response) / (number of participants analyzed in the group) * 100.
Time Frame Baseline through 24 weeks and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable EULAR response data. Modified last observation carried forward (mLOCF) was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Overall Number of Participants Analyzed 328 327 328
Measure Type: Number
Unit of Measure: percentage of participants
Week 24- Good 17.7 16.2 14.3
Week 24 - Moderate 41.5 38.5 30.8
Week 24 - No Response 40.9 45.3 54.9
Week 52 - Good 18.6 14.7 15.9
Week 52 - Moderate 37.5 39.1 29.0
Week 52 - No Response 43.9 46.2 55.2
7.Secondary Outcome
Title Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores
Hide Description SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, 2 component scores (CS), physical CS (PCS) and mental CS (MCS). Domain scores were calculated by summing each item for each domain and transforming scores into a 0-100 scale. Higher scores indicated better health status. If < 50% of the questions within a domain were answered, raw scores were not calculated. PCS score consisted of physical functioning, bodily pain, role-physical, and general health scales. MCS score consisted of social functioning, vitality, mental health, and role-emotional scales. Both PCS and MCS range from 0-100. Higher score indicated better mental or physical health. LS means were calculated using ANCOVA with treatment, region as fixed factors and baseline as a covariate.
Time Frame Baseline, 24 weeks and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable SF-36 domain and summary scores. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Overall Number of Participants Analyzed 320 322 323
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Physical functioning - Week 24 Number Analyzed 320 participants 322 participants 323 participants
2.70  (0.48) 3.16  (0.47) 2.06  (0.47)
Physical functioning - Week 52 Number Analyzed 320 participants 322 participants 323 participants
2.15  (0.50) 3.22  (0.49) 1.82  (0.49)
Bodily pain - Week 24 Number Analyzed 319 participants 322 participants 323 participants
4.07  (0.46) 4.08  (0.45) 2.52  (0.45)
Bodily pain - Week 52 Number Analyzed 319 participants 322 participants 323 participants
3.77  (0.47) 4.48  (0.46) 2.32  (0.46)
RL - physical problems - Week 24 Number Analyzed 320 participants 322 participants 323 participants
2.77  (0.46) 3.64  (0.46) 1.99  (0.45)
RL - physical problems - Week 52 Number Analyzed 320 participants 322 participants 323 participants
3.01  (0.47) 3.79  (0.46) 1.82  (0.46)
RL - emotional problems- Week 24 Number Analyzed 319 participants 322 participants 323 participants
3.20  (0.60) 4.81  (0.59) 2.91  (0.59)
RL - emotional problems- Week 52 Number Analyzed 319 participants 322 participants 323 participants
2.84  (0.61) 4.34  (0.59) 2.56  (0.59)
GH Perception - Week 24 Number Analyzed 319 participants 322 participants 323 participants
2.60  (0.41) 3.72  (0.40) 2.54  (0.40)
GH Perception - Week 52 Number Analyzed 319 participants 322 participants 323 participants
2.89  (0.42) 3.41  (0.41) 2.18  (0.41)
Mental Health - Week 24 Number Analyzed 319 participants 322 participants 323 participants
3.39  (0.53) 4.47  (0.53) 3.28  (0.52)
Mental Health - Week 52 Number Analyzed 319 participants 322 participants 323 participants
3.01  (0.55) 4.37  (0.54) 3.10  (0.54)
Social function - Week 24 Number Analyzed 319 participants 322 participants 323 participants
3.25  (0.53) 4.18  (0.52) 2.79  (0.52)
Social function - Week 52 Number Analyzed 319 participants 322 participants 323 participants
3.04  (0.53) 3.99  (0.52) 2.87  (0.52)
Vitality - Week 24 Number Analyzed 319 participants 322 participants 323 participants
3.43  (0.50) 4.41  (0.49) 2.99  (0.48)
Vitality - Week 52 Number Analyzed 319 participants 322 participants 323 participants
3.10  (0.51) 3.96  (0.50) 3.02  (0.49)
PCS - Week 24 Number Analyzed 319 participants 322 participants 323 participants
2.80  (0.43) 3.08  (0.43) 1.76  (0.42)
PCS - Week 52 Number Analyzed 319 participants 322 participants 323 participants
2.79  (0.44) 3.30  (0.43) 1.55  (0.43)
MCS - Week 24 Number Analyzed 319 participants 322 participants 323 participants
3.34  (0.56) 4.74  (0.55) 3.33  (0.55)
MCS - Week 52 Number Analyzed 319 participants 322 participants 323 participants
2.98  (0.57) 4.27  (0.56) 3.22  (0.56)
8.Secondary Outcome
Title Change From Baseline in Brief Fatigue Inventory (BFI) Individual Items and Impact Score
Hide Description The BFI is a brief participant-reported questionnaire for the rapid assessment of fatigue severity and the impact of fatigue on daily functioning in the past 24 hours. The BFI contains 10 items; however, Item 1 is not included in the scoring of the scale as it asks about usual fatigue over the past week with the participant answering 'yes' or 'no'. The remaining 9 items assess fatigue severity (3 items) and impact of fatigue on daily functioning (6 items) using an 11-point numeric scale, with 0=no fatigue and 10=fatigue as bad as you can imagine. The fatigue impact subscale score is the average of the non-missing responses to 6 items: general activity, mood, walking ability, normal work, relations with other people, and enjoyment of life. If more than 3 items within the fatigue impact subscale were not answered by a participant, the subscale is set to missing. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Time Frame Baseline, 24 weeks and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable BFI data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Overall Number of Participants Analyzed 320 322 323
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Fatigue-Now - Week 24 Number Analyzed 320 participants 322 participants 323 participants
-0.86  (0.14) -1.12  (0.13) -0.61  (0.13)
Fatigue-Now - Week 52 Number Analyzed 320 participants 322 participants 323 participants
-0.79  (0.14) -1.01  (0.13) -0.56  (0.13)
Fatigue-Usual - Week 24 Number Analyzed 320 participants 322 participants 323 participants
-0.93  (0.13) -1.06  (0.13) -0.61  (0.13)
Fatigue-Usual - Week 52 Number Analyzed 320 participants 322 participants 323 participants
-0.91  (0.14) -0.97  (0.13) -0.66  (0.13)
Fatigue-Worst - Week 24 Number Analyzed 320 participants 322 participants 323 participants
-0.98  (0.14) -1.22  (0.14) -0.71  (0.14)
Fatigue-Worst - Week 52 Number Analyzed 320 participants 322 participants 323 participants
-1.22  (0.15) -1.19  (0.14) -0.81  (0.14)
General Activity - Week 24 Number Analyzed 320 participants 322 participants 323 participants
-0.93  (0.14) -1.09  (0.13) -0.61  (0.13)
General Activity - Week 52 Number Analyzed 320 participants 322 participants 323 participants
-1.03  (0.14) -1.07  (0.13) -0.61  (0.13)
Mood - Week 24 Number Analyzed 320 participants 322 participants 323 participants
-0.67  (0.14) -1.01  (0.14) -0.47  (0.14)
Mood - Week 52 Number Analyzed 320 participants 322 participants 323 participants
-0.86  (0.14) -0.82  (0.14) -0.53  (0.14)
Walking Ability - Week 24 Number Analyzed 320 participants 322 participants 323 participants
-0.92  (0.15) -1.02  (0.14) -0.44  (0.14)
Walking Ability - Week 52 Number Analyzed 320 participants 322 participants 323 participants
-0.88  (0.14) -0.98  (0.14) -0.45  (0.14)
Normal Work - Week 24 Number Analyzed 320 participants 322 participants 322 participants
-0.78  (0.14) -1.07  (0.14) -0.48  (0.14)
Normal Work - Week 52 Number Analyzed 320 participants 322 participants 323 participants
-0.88  (0.14) -1.00  (0.14) -0.52  (0.14)
Relations with Other - Week 24 Number Analyzed 320 participants 322 participants 322 participants
-0.39  (0.14) -0.64  (0.14) -0.13  (0.14)
Relations with Other - Week 52 Number Analyzed 320 participants 322 participants 323 participants
-0.47  (0.14) -0.46  (0.14) -0.16  (0.14)
Enjoyment of Life - Week 24 Number Analyzed 320 participants 322 participants 322 participants
-0.58  (0.15) -0.82  (0.15) -0.36  (0.14)
Enjoyment of Life - Week 52 Number Analyzed 320 participants 322 participants 323 participants
-0.66  (0.15) -0.74  (0.14) -0.46  (0.14)
Fatigue Impact Subscale- Week 24 Number Analyzed 320 participants 322 participants 323 participants
-0.71  (0.13) -0.93  (0.13) -0.42  (0.13)
Fatigue Impact Subscale- Week 52 Number Analyzed 320 participants 322 participants 323 participants
-0.80  (0.13) -0.83  (0.13) -0.46  (0.13)
9.Secondary Outcome
Title Change From Baseline in Duration of Morning Stiffness (Minutes)
Hide Description The Investigator asks participants about the duration of their morning stiffness (in minutes) in and around the joints and records the duration. The Investigator should ask the participants about duration of morning stiffness on the day prior to the study visit to capture actual symptoms. If morning stiffness duration is longer than 12 hours (720 minutes), it was truncated to 720 minutes for statistical presentations and analyses. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Time Frame Baseline, 24 weeks and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable morning stiffness data; mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Overall Number of Participants Analyzed 307 319 314
Least Squares Mean (Standard Error)
Unit of Measure: minutes
Week 24 Number Analyzed 306 participants 318 participants 313 participants
-41.2  (5.0) -32.0  (4.8) -34.5  (4.9)
Week 52 Number Analyzed 307 participants 319 participants 314 participants
-41.4  (5.2) -31.2  (5.0) -37.3  (5.1)
10.Secondary Outcome
Title Change From Baseline in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores
Hide Description The BPI-SF is a self-reported scale that measures the severity of pain based on the worst pain, least pain, average pain experienced during the past 24-hours and pain based on the pain right now with scores ranging from 0 (no pain) to 10 (pain as severe as you can imagine). Pain interference score is the average of the responses in past 24-hours to 7 items: general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life [each item scored from 0 (does not interfere) to 10 (completely interferes)]. If more than 3 items of the Pain Interference Score are not answered by a participant, the score were set to missing. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Time Frame Baseline, 24 weeks and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable BPI-SF scores. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Overall Number of Participants Analyzed 320 322 323
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Pain-Worst - Week 24 -1.1  (0.1) -1.1  (0.1) -0.7  (0.1)
Pain-Worst - Week 52 -1.1  (0.1) -1.3  (0.1) -0.8  (0.1)
Pain-Least - Week 24 -0.3  (0.1) -0.6  (0.1) -0.1  (0.1)
Pain-Least - Week 52 -0.3  (0.1) -0.6  (0.1) -0.1  (0.1)
Pain-Average - Week 24 -0.8  (0.1) -0.9  (0.1) -0.3  (0.1)
Pain-Average - Week 52 -0.7  (0.1) -1.0  (0.1) -0.3  (0.1)
Pain-Now - Week 24 -1.1  (0.1) -1.2  (0.1) -0.5  (0.1)
Pain-Now - Week 52 -1.0  (0.1) -1.3  (0.1) -0.5  (0.1)
General Activity - Week 24 -1.0  (0.1) -1.0  (0.1) -0.6  (0.1)
General Activity - Week 52 -1.0  (0.1) -1.2  (0.1) -0.8  (0.1)
Mood - Week 24 -0.9  (0.1) -1.0  (0.1) -0.6  (0.1)
Mood - Week 52 -1.0  (0.1) -1.1  (0.1) -0.7  (0.1)
Walking Ability - Week 24 -0.9  (0.1) -1.2  (0.1) -0.5  (0.1)
Walking Ability - Week 52 -0.8  (0.1) -1.1  (0.1) -0.6  (0.1)
Normal Work - Week 24 -1.0  (0.1) -1.0  (0.1) -0.6  (0.1)
Normal Work - Week 52 -0.9  (0.1) -1.1  (0.1) -0.6  (0.1)
Relations with Other - Week 24 -0.5  (0.1) -0.6  (0.1) -0.3  (0.1)
Relations with Other - Week 52 -0.5  (0.1) -0.5  (0.1) -0.3  (0.1)
Sleep - Week 24 -1.0  (0.1) -1.1  (0.1) -0.4  (0.1)
Sleep - Week 52 -0.9  (0.1) -1.0  (0.1) -0.5  (0.1)
Enjoyment of Life - Week 24 -0.8  (0.1) -1.2  (0.1) -0.5  (0.1)
Enjoyment of Life - Week 52 -0.9  (0.1) -1.1  (0.1) -0.5  (0.1)
Pain Interference Score - Week 24 -0.89  (0.12) -1.02  (0.12) -0.50  (0.12)
Pain Interference Score - Week 52 -0.85  (0.12) -1.00  (0.12) -0.58  (0.12)
11.Secondary Outcome
Title Percentage of Participants With Major Clinical Response (MCR) During 52 Weeks
Hide Description [Not Specified]
Time Frame Baseline through 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Zero participants analyzed. Per protocol and statistical analysis plan (SAP) amendments, the major clinical response classification was not collected for analysis.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
12.Secondary Outcome
Title Percentage of Participants With Change From Baseline in mTSS Less Than or Equal to (≤) 0
Hide Description The mTSS quantifies the extent of bone erosions and joint space narrowing for 44 and 42 joints. X-rays of the hands/wrists and feet are scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (ankylosis or complete dislocation). Erosions scores (range=0 to 220 for 44 joints) and narrowing scores (range=0 to 168 for 42 joints) were added to obtain the mTSS (range = 0 [normal] to 388 [maximal disease]). Percentage of participants = (number of participants with mTSS ≤0 at Week 24) / (total number of participants analyzed in the group) * 100.
Time Frame Baseline through 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable mTSS data. A linear extrapolation method was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

At Week 16, NR received a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Overall Number of Participants Analyzed 295 304 306
Measure Type: Number
Unit of Measure: percentage of participants
61.0 61.8 56.2
13.Secondary Outcome
Title Change From Baseline to Week 52 in B Cell Subset Counts
Hide Description B cell subset counts are: cluster designation (CD)19+ B cell counts, Immature/transitional [CD19+immunoglobulin D (IgD)-CD27-], Mature naïve (CD19+IgD+CD27-), Non-switched memory (CD19+IgD+CD27+) and Memory (CD19+IgD-CD27+). A positive or negative change indicated an increase or decrease, respectively in B cell count. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Time Frame Baseline, 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable B cell subset counts data. mLOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Overall Number of Participants Analyzed 326 333 339
Least Squares Mean (Standard Error)
Unit of Measure: cells/microliter (cells/µL)
CD19+ Number Analyzed 326 participants 333 participants 339 participants
-57.1  (4.9) -60.9  (4.9) 0.7  (4.8)
CD19+IgD-CD27- Number Analyzed 321 participants 330 participants 336 participants
-3.1  (0.7) -3.9  (0.7) 0.2  (0.7)
CD19+IgD+CD27- Number Analyzed 321 participants 330 participants 336 participants
-89.4  (3.3) -92.4  (3.3) -3.5  (3.2)
CD19+IgD+CD27+ Number Analyzed 321 participants 330 participants 336 participants
9.5  (1.0) 8.9  (1.0) 1.0  (1.0)
CD19+IgD-CD27+ Number Analyzed 321 participants 330 participants 336 participants
19.7  (1.9) 20.6  (1.8) 3.2  (1.8)
14.Secondary Outcome
Title Population Pharmacokinetics (PK): Constant Clearance
Hide Description Population estimate of constant clearance as determined by population PK analysis. A 2-compartment model was used in PK modeling. Constant clearance is the PK parameter which describes the linear elimination of LY2127399 from serum.
Time Frame Baseline through 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of LY2127399 with evaluable LY2127399 PK data.
Arm/Group Title LY2127399
Hide Arm/Group Description:

A loading dose of 240 mg (2 injections of 120 mg) of LY2127399 followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W for 100 weeks or a loading dose of 180 mg of LY2127399 (2 injections of 90 mg) followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W for 100 weeks. At Weeks 16 and 52, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the 100-week treatment period or 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Overall Number of Participants Analyzed 825
Mean (95% Confidence Interval)
Unit of Measure: milliliter per hour (mL/h)
3.60
(3.46 to 3.73)
15.Secondary Outcome
Title Percentage of Participants Developing Anti-LY2127399 Antibodies
Hide Description Participants with treatment-emergent anti-drug antibodies (ADA) were participants who had any sample from baseline up to and through Week 24 that was a 4-fold increase (2-dilution increase) in immunogenicity titer over baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20). Percentage of participants with ADA=(number of participants with treatment-emergent ADA) / (number of participants assessed) * 100.
Time Frame Baseline through 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug with an evaluable baseline ADA result and a post-baseline ADA result. Participants missing an evaluable baseline result with all negative post-baseline results were included. Data after Week 16 for Week 16 NR were not included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Overall Number of Participants Analyzed 344 344 347
Measure Type: Number
Unit of Measure: percentage of participants
3.8 1.5 4.9
16.Secondary Outcome
Title Percentage of Participants With No Structural Progression at Week 52
Hide Description No structural progression is defined as the change in mTSS from baseline ≤0. The mTSS quantifies the extent of bone erosions and joint space narrowing for 44 and 42 joints. X-rays of the hands/wrists and feet are scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (ankylosis or complete dislocation). Erosions scores (range=0 to 220 for 44 joints) and narrowing scores (range=0 to 168 for 42 joints) were added to obtain the mTSS (range=0 [normal] to 388 [maximal disease]). Percentage of participants=(number of participants with mTSS ≤0 at Week 52) / (total number of participants analyzed in the group) * 100.
Time Frame Baseline through 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable mTSS data. A linear extrapolation method was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

At Week 16, NR received a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Overall Number of Participants Analyzed 295 304 306
Measure Type: Number
Unit of Measure: percentage of participants
55.6 57.6 53.9
17.Secondary Outcome
Title Change From Baseline to Week 24 in mTSS
Hide Description The mTSS quantifies the extent of bone erosions and joint space narrowing for 44 and 42 joints. X-rays of the hands/wrists and feet are scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (ankylosis or complete dislocation). Erosions scores (range=0 to 220 for 44 joints) and narrowing scores (range=0 to 168 for 42 joints) were added to obtain the mTSS (range=0 [normal] to 388 [maximal disease]). LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Time Frame Baseline, 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable mTSS data. A linear extrapolation method was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

At Week 16, NR received a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Overall Number of Participants Analyzed 295 304 306
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.63  (0.14) 0.45  (0.14) 0.82  (0.14)
18.Secondary Outcome
Title Change From Baseline in Serum Immunoglobulin (Ig) Levels
Hide Description Immunoglobulins (Ig), or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Change from baseline serum immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) levels are reported. A negative change indicated a decrease in Ig levels. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Time Frame Baseline, 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable serum Ig data. mLOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Overall Number of Participants Analyzed 342 342 347
Least Squares Mean (Standard Error)
Unit of Measure: grams/liter (g/L)
IgA -0.380  (0.028) -0.382  (0.028) -0.009  (0.028)
IgG -1.375  (0.096) -1.235  (0.097) -0.176  (0.096)
IgM -0.235  (0.016) -0.274  (0.016) -0.032  (0.016)
19.Secondary Outcome
Title Change From Baseline in Joint Space Narrowing Score and Bone Erosions Score (Components of mTSS)
Hide Description The mTSS quantifies the extent of bone erosions and joint space narrowing for 44 and 42 joints. X-rays of the hands/wrists and feet are scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (ankylosis or complete dislocation). Erosions scores (range=0 to 220 for 44 joints) and narrowing scores (range=0 to 168 for 42 joints) were added to obtain the mTSS (range=0 [normal] to 388 [maximal disease]). LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Time Frame Baseline, 24 weeks and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable mTSS data. A linear extrapolation method was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

At Week 16, NR received a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Overall Number of Participants Analyzed 295 304 306
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Joint Space Narrowing - Week 24 0.22  (0.09) 0.19  (0.09) 0.34  (0.09)
Joint Space Narrowing - Week 52 0.56  (0.16) 0.35  (0.16) 0.61  (0.16)
Bone Erosions - Week 24 0.40  (0.09) 0.26  (0.08) 0.48  (0.08)
Bone Erosions - Week 52 0.86  (0.17) 0.49  (0.17) 0.96  (0.17)
20.Secondary Outcome
Title American College of Rheumatology Percent Improvement (ACR-N)
Hide Description ACR-N is a continuous measure of clinical, laboratory, and functional outcomes in RA that characterizes percentage (%) of improvement in disease activity from baseline based on ACR core set. This index was calculated as minimum of either a) % change in TJ count, b) % change in SJ count, or c) the median % change of remaining 5 ACR core criteria: If ≥3 components of the 5 ACR core criteria were missing, then c) was set to missing; if any of 3 components a), b), or c) were missing, then ACR-N was set to missing. Percentage of improvement was truncated to range of -100 to 100 to minimize impact of outliers (greater values indicate greater % improvement) and negative scores indicate a decline. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline DAS28-CRP as a covariate.
Time Frame Baseline through 24 weeks and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable ACR-N data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Overall Number of Participants Analyzed 329 326 327
Least Squares Mean (Standard Error)
Unit of Measure: percentage of improvement
Week 24 2.0  (2.5) 2.1  (2.5) -6.9  (2.5)
Week 52 2.9  (2.5) 0.3  (2.5) -7.3  (2.5)
21.Secondary Outcome
Title Change From Baseline in Tender Joint Count (68 Joint Count)
Hide Description Tender joint count is the number of tender and painful joints determined for each participant by examination of 68 joints. Joints were assessed by pressure and joint manipulation on physical examination. Participants were asked for pain sensations on these manipulations and watched for spontaneous pain reactions. Any positive response on pressure, movement, or both was translated into a single tender-versus-nontender dichotomy. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Time Frame Baseline, 24 weeks and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable tender joint count data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Overall Number of Participants Analyzed 329 329 334
Least Squares Mean (Standard Error)
Unit of Measure: joint counts
Week 24 -7.41  (0.72) -7.88  (0.72) -6.40  (0.72)
Week 52 -7.88  (0.73) -8.09  (0.73) -5.72  (0.73)
22.Secondary Outcome
Title Change From Baseline in Swollen Joint Count (66 Joint Count)
Hide Description Swollen joint count is the number of swollen joints determined for each participant by examination of 66 joints. Joints were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Time Frame Baseline, 24 weeks and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable swollen joint count data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Overall Number of Participants Analyzed 329 329 334
Least Squares Mean (Standard Error)
Unit of Measure: joint counts
Week 24 -5.38  (0.49) -5.64  (0.49) -4.67  (0.49)
Week 52 -6.10  (0.49) -5.53  (0.49) -4.61  (0.49)
23.Secondary Outcome
Title Change From Baseline in Participant's Assessment of Pain [Visual Analog Scale (VAS)]
Hide Description Participant's assessment of their current arthritis pain using VAS ranged from 0 millimeters (mm) (no pain) to 100 mm (worst possible pain). A decrease in pain score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Time Frame Baseline, 24 weeks and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable participant's assessment of pain data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Overall Number of Participants Analyzed 329 327 328
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 24 -13.6  (1.2) -14.6  (1.2) -9.0  (1.2)
Week 52 -13.2  (1.2) -14.6  (1.2) -8.7  (1.2)
24.Secondary Outcome
Title Change From Baseline in Participant's Global Assessment of Disease Activity (VAS)
Hide Description Participant's assessment of their current arthritis disease activity using VAS ranged from 0 mm (no arthritis activity) to 100 mm (extremely active arthritis). A decrease in disease activity score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Time Frame Baseline, 24 weeks and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable participant's global assessment of disease activity data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Overall Number of Participants Analyzed 329 327 328
Least Squares Mean (Standard Error)
Unit of Measure: mm
Week 24 -13.2  (1.2) -15.1  (1.2) -11.0  (1.2)
Week 52 -13.1  (1.2) -15.2  (1.2) -10.8  (1.2)
25.Secondary Outcome
Title Change From Baseline in Physician's Global Assessment of Disease Activity (VAS)
Time Frame Baseline, 24 weeks and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable physician's global assessment of disease activity data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Overall Number of Participants Analyzed 321 315 314
Least Squares Mean (Standard Error)
Unit of Measure: mm
Week 24 -20.7  (1.3) -22.0  (1.3) -17.2  (1.3)
Week 52 -20.4  (1.3) -20.6  (1.3) -17.8  (1.3)
26.Secondary Outcome
Title Change From Baseline to Week 52 in HAQ-DI
Hide Description The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty [0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (severe disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Time Frame Baseline, 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable HAQ-DI data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Overall Number of Participants Analyzed 329 327 328
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.24  (0.03) -0.30  (0.03) -0.18  (0.03)
27.Secondary Outcome
Title Change From Baseline to Week 52 in Absolute B Cell Counts
Hide Description Cell-surface marker cluster designation (CD) 3 negative, CD20 positive (CD3-CD20+) defines total mature B cells. B-lymphocyte antigen CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all mature B cells. A positive or negative change indicated an increase or decrease, respectively in B cell count. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Time Frame Baseline, 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable CD3-CD20+ B cell counts. mLOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Overall Number of Participants Analyzed 343 344 348
Least Squares Mean (Standard Error)
Unit of Measure: cells/microliter (cells/µL)
-56.5  (4.5) -58.6  (4.5) -6.8  (4.5)
28.Secondary Outcome
Title Percentage of Participants With ACR20 at Week 52
Hide Description ACR Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis (RA). ACR20 Responder: had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, HAQ-DI (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and CRP. Percentage of participants achieving ACR20 response=(number of ACR20 responders) /( number of participants treated) * 100. All NR at Week 16 as well as all participants who discontinued study treatment at any time for any reason were defined as NR starting at that time-point and going forward, including Week 52 endpoint.
Time Frame Baseline through 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable ACR20 responder data. If participant's CRP was missing, last post-baseline value was used. If ACR was missing after carrying forward CRP, last post-baseline ACR response was used. Data after Week 16 for Week 16 NR were not included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Overall Number of Participants Analyzed 330 332 335
Measure Type: Number
Unit of Measure: percentage of participants
7.9 9.6 10.7
29.Secondary Outcome
Title Time to ACR20 Response
Hide Description ACR Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis (RA). ACR20 Responder: had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, HAQ-DI (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and CRP. The Kaplan-Meier was used to estimate time to ACR20 response over the Treatment Period (52 weeks). Time to ACR20 response = (Date of the first post-baseline visit during the Treatment Period meeting ACR20 response criteria - Date of first injection of study treatment + 1) / 7. Week 16 NR are counted as responders if they responded prior to Week 16. Otherwise, they are censored at the date of the Week 16 injection. All participants ongoing at Week 52 and had not yet responded are censored at the date of the Week 52 visit.
Time Frame Baseline through 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable ACR20 responder data. The number of participants censored are 128 (120 mg LY2127399), 123 (90 mg LY2127399) and 162 (placebo).
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

At Week 16, NR received a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Overall Number of Participants Analyzed 327 327 329
Median (95% Confidence Interval)
Unit of Measure: weeks
16.1
(12.1 to 16.4)
16.1
(12.3 to 20.0)
20.1
(16.4 to 24.7)
30.Secondary Outcome
Title Change From Baseline in CRP
Hide Description CRP is an indicator of inflammation. A negative change indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.
Time Frame Baseline, 24 weeks and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable CRP data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Overall Number of Participants Analyzed 329 328 334
Least Squares Mean (Standard Error)
Unit of Measure: milligrams/liter (mg/L)
Week 24 -3.30  (0.83) -2.03  (0.84) -0.54  (0.83)
Week 52 -1.72  (0.96) -2.04  (0.97) -0.40  (0.96)
31.Other Pre-specified Outcome
Title Number of Participants Who Died During Post-Treatment Follow-Up Period
Hide Description [Not Specified]
Time Frame Discontinuation from study treatment up to 48 weeks during follow-up period
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug and entered post-treatment follow-up period.
Arm/Group Title 120 mg LY2127399 90 mg LY2127399 Placebo
Hide Arm/Group Description:

Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W.

At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W.

At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

At Week 16, NR received a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.

Overall Number of Participants Analyzed 293 303 307
Measure Type: Count of Participants
Unit of Measure: Participants
0 1 2
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title LY 120 mg Q4W, Randomized Treatment Period 1 LY 90 mg Q2W, Randomized Treatment Period 1 Placebo, Randomized Treatment Period 1 LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Rescue Period LY 90 mg Q2W, Rescue Period Placebo to LY 90 mg Q2W (Week 16), Rescue Period LY 120 mg Q4W, Treatment Period 2 LY 90 mg Q2W, Treatment Period 2 Placebo to LY 120 mg Q4W (Week 52), Treatment Period 2 Placebo to LY 90 mg Q2W (Week 52), Treatment Period 2 LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Treatment Period 2 Placebo to LY 90 mg Q2W (Week 16), Treatment Period 2 LY 120 mg Q4W, Follow-up Period LY 90 mg Q2W, Follow-up Period Placebo to LY 120 mg Q4W (Week 52), Follow-up Period Placebo to LY 90 mg Q2W (Week 52), Follow-up Period LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Follow-up Period Placebo to LY 90 mg Q2W (Week 16), Follow-up Period Placebo, Follow-up Period
Hide Arm/Group Description

A loading dose of 240 mg of LY2127399 (2 injections of 120 mg) followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W for 52 weeks during Treatment Period 1. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the 52-week Treatment Period 1. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

The Randomized Treatment Period 1 was defined as the time all data was collected during the Treatment Period 1, excluding the data collected after the date of the Week 16 injection for the Week 16 NR.

A loading dose of 180 mg of LY2127399 (2 injections of 90 mg) followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

The Randomized Treatment Period 1 was defined as the time all data was collected during the Treatment Period 1, excluding the data collected after the date of the Week 16 injection for the Week 16 NR.

A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

The Randomized Treatment Period 1 was defined as the time all data was collected during the Treatment Period 1, excluding the data collected after the date of the Week 16 injection for the Week 16 NR.

A loading dose of 240 mg of LY2127399 (2 injections of 120 mg) followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W for 16 weeks during Treatment Period 1. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 52-week Treatment Period 1.

The Rescue Treatment Period was defined as all data collected after the date of the Week 16 injection during the Treatment Period 1 for Week 16 NR.

A loading dose of 180 mg of LY2127399 (2 injections of 90 mg) followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W for 16 weeks during Treatment Period 1.

At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 52-week Treatment Period 1.

The Rescue Treatment Period was defined as all data collected after the date of the Week 16 injection during the Treatment Period 1 for Week 16 NR.

A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 16 weeks during Treatment Period 1.

At Week 16, NR received a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 52-week Treatment Period 1.

The Rescue Treatment Period was defined as all data collected after the date of the Week 16 injection during the Treatment Period 1 for Week 16 NR.

A loading dose of 240 mg of LY2127399 (2 injections of 120 mg) followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W for 52 weeks during Treatment Period 1. At Week 16, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the 52-week Treatment Period 1. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

Treatment Period 2 was defined as all data collected from Week 52 to Week 100 during non-blinded Treatment Period 2.

A loading dose of 180 mg of LY2127399 (2 injections of 90 mg) followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, both Week 16 responders and NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

At Week 52, both Week 16 responders and NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

Treatment Period 2 was defined as all data collected from Week 52 to Week 100 during non-blinded Treatment Period 2.

A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, Week 16 responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

At Week 52, Week 16 responders were randomized to receive 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2

Treatment Period 2 was defined as all data collected from Week 52 to Week 100 during non-blinded Treatment Period 2.

A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, Week 16 responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

At Week 52, Week 16 responders were randomized to receive 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q4W for the rest of the Treatment Period 2

Treatment Period 2 was defined as all data collected from Week 52 to Week 100 during non-blinded Treatment Period 2.

A loading dose of 240 mg of LY2127399 (2 injections of 120 mg) followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W for 16 weeks during Treatment Period 1. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, Week 16 NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 52-week Treatment Period 1.

During non-blinded Treatment Period 2, Week 16 NR received 1 injection of 90 mg of LY2127399.

Treatment Period 2 was defined as all data collected from Week 52 to Week 100 during non-blinded Treatment Period 2.

A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 16 weeks during Treatment Period 1.

At Week 16, Week 16 NR received a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 52-week Treatment Period 1.

During non-blinded Treatment Period 2, Week 16 NR received 1 injection of 90 mg of LY2127399.

Treatment Period 2 was defined as all data collected from Week 52 to Week 100 during non-blinded Treatment Period 2.

A loading dose of 240 mg of LY2127399 (2 injections of 120 mg) followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W for 52 weeks during Treatment Period 1. At Week 16, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the 52-week Treatment Period 1. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.

The Post-Treatment Follow-Up Period started after Week 100 or the early discontinuation visit and lasted up to 48 weeks following the last injection of study treatment.

A loading dose of 180 mg of LY2127399 (2 injections of 90 mg) followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, both Week 16 responders and NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1.

At Week 52, both Week 16 responders and NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.

The Post-Treatment Follow-Up Period started after Week 100 or the early discontinuation visit and lasted up to 48 weeks following the last injection of study treatment.

A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, Week 16 responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

At Week 52, Week 16 responders were randomized to receive 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2

The Post-Treatment Follow-Up Period started after Week 100 or the early discontinuation visit and lasted up to 48 weeks following the last injection of study treatment.

A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, Week 16 responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

At Week 52, Week 16 responders were randomized to receive 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q4W for the rest of the Treatment Period 2

The Post-Treatment Follow-Up Period started after Week 100 or the early discontinuation visit and lasted up to 48 weeks following the last injection of study treatment.

A loading dose of 240 mg of LY2127399 (2 injections of 120 mg) followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W for 16 weeks during Treatment Period 1. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W.

At Week 16, Week 16 NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 52-week Treatment Period 1.

During non-blinded Treatment Period 2, Week 16 NR received 1 injection of 90 mg of LY2127399.

The Post-Treatment Follow-Up Period started after Week 100 or the early discontinuation visit and lasted up to 48 weeks following the last injection of study treatment.

A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 16 weeks during Treatment Period 1.

At Week 16, Week 16 NR received a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 52-week Treatment Period 1.

During non-blinded Treatment Period 2, Week 16 NR received 1 injection of 90 mg of LY2127399.

The Post-Treatment Follow-Up Period started after Week 100 or the early discontinuation visit and lasted up to 48 weeks following the last injection of study treatment.

A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1.

The Post-Treatment Follow-Up Period started after Week 52 or the early discontinuation visit and lasted up to 48 weeks following the last injection of study treatment.

All-Cause Mortality
LY 120 mg Q4W, Randomized Treatment Period 1 LY 90 mg Q2W, Randomized Treatment Period 1 Placebo, Randomized Treatment Period 1 LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Rescue Period LY 90 mg Q2W, Rescue Period Placebo to LY 90 mg Q2W (Week 16), Rescue Period LY 120 mg Q4W, Treatment Period 2 LY 90 mg Q2W, Treatment Period 2 Placebo to LY 120 mg Q4W (Week 52), Treatment Period 2 Placebo to LY 90 mg Q2W (Week 52), Treatment Period 2 LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Treatment Period 2 Placebo to LY 90 mg Q2W (Week 16), Treatment Period 2 LY 120 mg Q4W, Follow-up Period LY 90 mg Q2W, Follow-up Period Placebo to LY 120 mg Q4W (Week 52), Follow-up Period Placebo to LY 90 mg Q2W (Week 52), Follow-up Period LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Follow-up Period Placebo to LY 90 mg Q2W (Week 16), Follow-up Period Placebo, Follow-up Period
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
LY 120 mg Q4W, Randomized Treatment Period 1 LY 90 mg Q2W, Randomized Treatment Period 1 Placebo, Randomized Treatment Period 1 LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Rescue Period LY 90 mg Q2W, Rescue Period Placebo to LY 90 mg Q2W (Week 16), Rescue Period LY 120 mg Q4W, Treatment Period 2 LY 90 mg Q2W, Treatment Period 2 Placebo to LY 120 mg Q4W (Week 52), Treatment Period 2 Placebo to LY 90 mg Q2W (Week 52), Treatment Period 2 LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Treatment Period 2 Placebo to LY 90 mg Q2W (Week 16), Treatment Period 2 LY 120 mg Q4W, Follow-up Period LY 90 mg Q2W, Follow-up Period Placebo to LY 120 mg Q4W (Week 52), Follow-up Period Placebo to LY 90 mg Q2W (Week 52), Follow-up Period LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Follow-up Period Placebo to LY 90 mg Q2W (Week 16), Follow-up Period Placebo, Follow-up Period
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   19/345 (5.51%)      17/345 (4.93%)      17/348 (4.89%)      3/58 (5.17%)      3/62 (4.84%)      2/90 (2.22%)      1/57 (1.75%)      1/73 (1.37%)      2/27 (7.41%)      1/31 (3.23%)      0/13 (0.00%)      0/22 (0.00%)      9/241 (3.73%)      14/303 (4.62%)      1/27 (3.70%)      1/27 (3.70%)      5/52 (9.62%)      4/85 (4.71%)      14/168 (8.33%)    
Blood and lymphatic system disorders                                       
Anaemia  1  1/345 (0.29%)  1 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 1/85 (1.18%)  1 0/168 (0.00%)  0
Iron deficiency anaemia  1  0/345 (0.00%)  0 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 1/73 (1.37%)  1 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Pancytopenia  1  0/345 (0.00%)  0 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 1/241 (0.41%)  1 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Cardiac disorders                                       
Acute myocardial infarction  1  0/345 (0.00%)  0 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 1/303 (0.33%)  1 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 1/168 (0.60%)  1
Arrhythmia  1  0/345 (0.00%)  0 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 1/303 (0.33%)  1 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Atrial fibrillation  1  0/345 (0.00%)  0 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 1/168 (0.60%)  1
Cardiac failure chronic  1  0/345 (0.00%)  0 0/345 (0.00%)  0 1/348 (0.29%)  1 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Cardiogenic shock  1  0/345 (0.00%)  0 0/345 (0.00%)  0 1/348 (0.29%)  1 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Congestive cardiomyopathy  1  0/345 (0.00%)  0 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 1/168 (0.60%)  1
Coronary artery insufficiency  1  0/345 (0.00%)  0 0/345 (0.00%)  0 1/348 (0.29%)  1 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Myocardial infarction  1  1/345 (0.29%)  1 0/345 (0.00%)  0 2/348 (0.57%)  2 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 1/303 (0.33%)  1 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Sick sinus syndrome  1  0/345 (0.00%)  0 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 1/62 (1.61%)  1 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Eye disorders                                       
Ulcerative keratitis  1  1/345 (0.29%)  1 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Gastrointestinal disorders                                       
Gastric haemorrhage  1  1/345 (0.29%)  1 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Gastric ulcer  1  0/345 (0.00%)  0 0/345 (0.00%)  0 1/348 (0.29%)  1 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Hiatus hernia  1  0/345 (0.00%)  0 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 1/303 (0.33%)  1 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Mechanical ileus  1  0/345 (0.00%)  0 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 1/241 (0.41%)  1 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Nausea  1  0/345 (0.00%)  0 1/345 (0.29%)  1 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Pancreatitis acute  1  1/345 (0.29%)  1 1/345 (0.29%)  1 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Pancreatitis chronic  1  0/345 (0.00%)  0 1/345 (0.29%)  1 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Vomiting  1  0/345 (0.00%)  0 1/345 (0.29%)  1 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
General disorders                                       
Death  1  0/345 (0.00%)  0 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 1/85 (1.18%)  1 0/168 (0.00%)  0
Device dislocation  1  0/345 (0.00%)  0 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 1/90 (1.11%)  1 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Non-cardiac chest pain  1  0/345 (0.00%)  0 0/345 (0.00%)  0 1/348 (0.29%)  1 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Pyrexia  1  0/345 (0.00%)  0 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 1/241 (0.41%)  1 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Hepatobiliary disorders                                       
Cholecystitis  1  0/345 (0.00%)  0 0/345 (0.00%)  0 1/348 (0.29%)  1 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Cholelithiasis  1  0/345 (0.00%)  0 0/345 (0.00%)  0 1/348 (0.29%)  1 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Immune system disorders                                       
Drug hypersensitivity  1  0/345 (0.00%)  0 1/345 (0.29%)  1 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Infections and infestations                                       
Bacterial infection  1  0/345 (0.00%)  0 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 1/241 (0.41%)  1 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Bronchitis  1  1/345 (0.29%)  1 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Cellulitis  1  0/345 (0.00%)  0 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 1/57 (1.75%)  1 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 1/52 (1.92%)  1 0/85 (0.00%)  0 0/168 (0.00%)  0
Device related infection  1  0/345 (0.00%)  0 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 1/52 (1.92%)  1 0/85 (0.00%)  0 1/168 (0.60%)  1
Diverticulitis  1  1/345 (0.29%)  1 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Enteritis infectious  1  1/345 (0.29%)  1 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Gastroenteritis  1  0/345 (0.00%)  0 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 1/62 (1.61%)  1 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 1/168 (0.60%)  1
Herpes zoster  1  2/345 (0.58%)  2 1/345 (0.29%)  1 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Infective tenosynovitis  1  0/345 (0.00%)  0 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 1/168 (0.60%)  1
Influenza  1  0/345 (0.00%)  0 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 1/241 (0.41%)  1 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Peritonitis  1  1/345 (0.29%)  1 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Pneumonia  1  0/345 (0.00%)  0 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 1/90 (1.11%)  1 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 1/303 (0.33%)  1 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 1/85 (1.18%)  1 0/168 (0.00%)  0
Post procedural infection  1  0/345 (0.00%)  0 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 1/85 (1.18%)  1 0/168 (0.00%)  0
Pseudomembranous colitis  1  0/345 (0.00%)  0 0/345 (0.00%)  0 1/348 (0.29%)  1 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Pyelonephritis acute  1  0/345 (0.00%)  0 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 1/241 (0.41%)  1 0/303 (0.00%)  0 0/27 (0.00%)  0 1/27 (3.70%)  1 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Pyelonephritis chronic  1  0/345 (0.00%)  0 1/345 (0.29%)  1 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Sepsis  1  1/345 (0.29%)  1 0/345 (0.00%)  0 1/348 (0.29%)  1 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Urinary tract infection  1  1/345 (0.29%)  1 0/345 (0.00%)  0 0/348 (0.00%)  0 0/58 (0.00%)  0 0/62 (0.00%)  0 0/90 (0.00%)  0 0/57 (0.00%)  0 0/73 (0.00%)  0 0/27 (0.00%)  0 0/31 (0.00%)  0 0/13 (0.00%)  0 0/22 (0.00%)  0 0/241 (0.00%)  0 0/303 (0.00%)  0 0/27 (0.00%)  0 0/27 (0.00%)  0 0/52 (0.00%)  0 0/85 (0.00%)  0 0/168 (0.00%)  0
Injury, poisoning and procedural complications                                       
Femoral neck fracture  1  0/345 (0.00%)