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Trial record 8 of 133 for:    Drug | "Connective Tissue Disease" | "Abatacept"

Efficacy at 24 Weeks and Safety, Tolerability and Long Term Efficacy of Secukinumab (AIN457) in Patients With Active Rheumatoid Arthritis (RA) and an Inadequate Response to Anti-Tumor Necrosis Factor α (Anti-TNFα) Agents (CAIN457F2309 and CAIN457F2309E1) (NURTURE 1)

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ClinicalTrials.gov Identifier: NCT01350804
Recruitment Status : Completed
First Posted : May 10, 2011
Results First Posted : May 23, 2016
Last Update Posted : May 23, 2016
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Biological: AIN457
Biological: Placebo
Biological: Abatacept
Enrollment 551
Recruitment Details At baseline, participants were randomized to 1 of 4 treatment groups. Placebo non-responders at week16 were re-randomized to receive AIN457 75mg or AIN457 150mg. Placebo responders at Week16 were re-randomized to receive AIN457 75mg or AIN457 150mg at Week24. Fifteen participants from the placebo group discontinued prior to re-randomization.
Pre-assignment Details Abatacept responders at Week16 continued on abatacept and non-responders at Week 16 were re-randomized to begin either AIN457 75mg or AIN457 150mg at Week 24. Of the 551 core study participants, 254 participants entered the extension study.
Arm/Group Title AIN457 10mg/kg - 75 mg AIN457 10mg/kg - 150 mg Placebo Abatacept
Hide Arm/Group Description Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks. Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks. Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24. Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).
Period Title: Core Study
Started 138 137 138 138
Safety Set 137 [1] 136 [2] 139 [1] 137 [2]
Tratment Switch to AIN457 at Week 16 0 0 78 [3] 0
Treatment Switch to AIN457 at Week 24 0 0 45 37
Full Analysis Set 138 137 138 138
Completed 97 90 91 112
Not Completed 41 47 47 26
Reason Not Completed
Withdrawal by Subject             11             17             16             7
Study terminated by Sponsor             0             0             0             2
Protocol deviation             1             0             1             0
Physician Decision             1             0             1             3
Lost to Follow-up             3             0             2             1
Lack of Efficacy             16             19             18             5
Death             1             1             1             0
Adverse Event             8             10             8             8
[1]
1 participant actually received placebo; participant was reassigned to placebo for safety analysis.
[2]
1 participant did not receive treatment; therefore participant was not counted in safety analysis.
[3]
15 participantsdiscontinued prior to the treatment switch
Period Title: Extension Study, Weeks 52 - 260
Started 80 79 72 [1] 23 [1]
Completed 0 0 0 0
Not Completed 80 79 72 23
Reason Not Completed
Withdrawal by Subject             5             6             4             3
Study terminated by Sponsor             67             67             64             16
Physician Decision             1             0             2             0
Lost to Follow-up             0             1             0             0
Lack of Efficacy             4             4             0             1
Adverse Event             3             1             2             3
[1]
During the extension, these participants received AIN457.
Arm/Group Title AIN457 10mg/kg - 75 mg AIN457 10mg/kg - 150 mg Placebo Abatacept Total
Hide Arm/Group Description Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks. Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks. Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24. Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period). Total of all reporting groups
Overall Number of Baseline Participants 138 137 138 138 551
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 138 participants 137 participants 138 participants 138 participants 551 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
111
  80.4%
103
  75.2%
106
  76.8%
115
  83.3%
435
  78.9%
>=65 years
27
  19.6%
34
  24.8%
32
  23.2%
23
  16.7%
116
  21.1%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 138 participants 137 participants 138 participants 138 participants 551 participants
Female
119
  86.2%
109
  79.6%
115
  83.3%
107
  77.5%
450
  81.7%
Male
19
  13.8%
28
  20.4%
23
  16.7%
31
  22.5%
101
  18.3%
1.Primary Outcome
Title Percentage of Participants Achieving an American College of Rheumatology Response 20 (ACR20).
Hide Description ACR20 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 20% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient’s assessment of RA pain, patient’s global assessment of disease activity, physician’s global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR). The ACR20 response results at week 24 used non-responder imputation.
Time Frame week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set: the full analysis set was comprised of all randomized participants (excluding mis-randomized participants) who were assigned to study treatment.
Arm/Group Title AIN457 10mg/kg - 75 mg AIN457 10mg/kg - 150 mg Placebo Abatacept
Hide Arm/Group Description:
Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.
Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.
Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.
Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).
Overall Number of Participants Analyzed 138 137 138 138
Measure Type: Number
Unit of Measure: Percentage of participants
28.3 30.7 18.1 42.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection AIN457 10mg/kg - 75 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0458
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.79
Confidence Interval (2-Sided) 95%
1.0 to 3.2
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection AIN457 10mg/kg - 150 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0152
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.02
Confidence Interval (2-Sided) 95%
1.1 to 3.5
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP)
Hide Description The DAS28 is a measure of disease activity in RA based on Swollen and Tender Joint Counts (out of a total of 28), hsCRP and the Patient’s Global Assessment of Disease Activity. A DAS28 score greater than 5.1 implies active disease, equal to or less than 3.2 low disease activity, and less than 2.6 remission. A negative change from baseline indicates improvement.
Time Frame baseline, week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the full analysis set were considered for the analysis. Participants with measurements at both baseline and week 24 were analyzed. The full analysis set was comprised of all randomized participants (excluding mis-randomized participants) who were assigned to study treatment.
Arm/Group Title AIN457 10mg/kg - 75 mg AIN457 10mg/kg - 150 mg Placebo Abatacept
Hide Arm/Group Description:
Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.
Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.
Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.
Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).
Overall Number of Participants Analyzed 116 108 44 84
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-1.47  (0.115) -1.47  (0.119) -1.02  (0.163) -2.07  (0.128)
3.Secondary Outcome
Title Change From Baseline in Stanford Health Assessment Questionnaire Disability Index (HAQ-DI)
Hide Description The HAQ-DI assesses a subject's level of functional ability and includes questions of fine movements of the upper extremity, locomotor activities of the lower extremity, and activities that involve both upper and lower extremities. There are 20 questions in 8 categories of functioning including dressing, rising, eating, walking, hygiene, reach, grip and usual activities. The stem of each item asks 'Over the past week, "are you able to..." perform a particular task'. Each item is scored on a 4 point scale from 0 - 3, representing normal, no difficulty (0), some difficulty (1), much difficulty (2) and unable to do (3). The disability index score is calculated as the mean of the available category scores, ranging from 0 to 3. A negative change from baseline indicates improvement.
Time Frame baseline, week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the full analysis set were considered for the analysis. Participants with measurements at both baseline and week 24 were analyzed. The full analysis set was comprised of all randomized participants (excluding mis-randomized participants) who were assigned to study treatment.
Arm/Group Title AIN457 10mg/kg - 75 mg AIN457 10mg/kg - 150 mg Placebo Abatacept
Hide Arm/Group Description:
Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.
Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.
Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.
Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).
Overall Number of Participants Analyzed 117 110 44 86
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-0.30  (0.049) -0.39  (0.051) -0.26  (0.065) -0.61  (0.053)
4.Secondary Outcome
Title Percentage of Participants Achieving ACR50
Hide Description ACR50 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 50% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient’s assessment of RA pain, patient’s global assessment of disease activity, physician’s global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR). The ACR50 response results at week 24 used non-responder imputation.
Time Frame week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set: the full analysis set was comprised of all randomized participants (excluding mis-randomized participants) who were assigned to study treatment.
Arm/Group Title AIN457 10mg/kg - 75 mg AIN457 10mg/kg - 150 mg Placebo Abatacept
Hide Arm/Group Description:
Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.
Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.
Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.
Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).
Overall Number of Participants Analyzed 138 137 138 138
Measure Type: Number
Unit of Measure: Percentage of participants
11.6 16.8 9.4 27.5
5.Secondary Outcome
Title Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation
Hide Description ACR20, ACR 50 and ACR 70 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 20%, 50% and/or 70% improvement, respectively, in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient’s assessment of RA pain, patient’s global assessment of disease activity, physician’s global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR).
Time Frame baseline, weeks 1, 2, 4, 8, 12, 16, 20 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the full analysis set were considered for the analysis. Participants with missing data were considered non-responders at the respective time point. Placebo and Abatacept participants were considered non-responders from the time of treatment switch.
Arm/Group Title AIN457 10mg/kg - 75 mg AIN457 10mg/kg - 150 mg Placebo Abatacept
Hide Arm/Group Description:
Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.
Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.
Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.
Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).
Overall Number of Participants Analyzed 138 137 138 138
Measure Type: Number
Unit of Measure: Percentage of participants
ACR20, week 1 21.0 17.5 7.2 10.9
ACR20, week 2 24.6 21.2 12.3 23.9
ACR20, week 4 34.1 27.0 21.7 31.2
ACR20, week 8 35.5 41.6 21.0 49.3
ACR20, week 12 28.3 33.6 24.6 47.1
ACR20, week 16 34.1 39.4 23.2 51.4
ACR20, week 20 26.8 38.0 18.1 47.8
ACR20, week 24 28.3 30.7 18.1 42.8
ACR50, week 1 6.5 2.9 0.7 1.4
ACR50, week 2 5.1 8.8 2.9 2.9
ACR50, week 4 9.4 10.2 2.9 7.2
ACR50, week 8 7.2 15.3 10.1 18.8
ACR50, week 12 8.7 13.1 10.1 22.5
ACR50, week 16 13.8 20.4 9.4 23.9
ACR50, week 20 12.3 18.2 8.0 26.8
ACR50, week 24 11.6 16.8 9.4 27.5
ACR70, week 1 0.7 0.7 0.0 0.7
ACR70, week 2 1.4 0.7 1.4 0.7
ACR70, week 4 4.3 2.9 1.4 1.4
ACR70, week 8 1.4 4.4 2.9 5.8
ACR70, week 12 2.2 2.9 2.9 9.4
ACR70, week 16 5.1 8.0 2.9 9.4
ACR70, week 20 4.3 7.3 5.8 10.1
ACR70, week 24 5.1 10.2 5.1 12.3
6.Secondary Outcome
Title Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data
Hide Description ACR20, ACR 50 and ACR 70 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 20%, 50% and/or 70% improvement, respectively, in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient’s assessment of RA pain, patient’s global assessment of disease activity, physician’s global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR). The ACR20, ACR50 and ACR70 response results from baseline up to week 52 were based on observed data, i.e. without imputation.
Time Frame baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the full analysis set were considered for the analysis. Participants with measurements at both baseline and each post-baseline time point were analyzed for that post-baseline time point. The full analysis set was comprised of all randomized participants (excluding mis-randomized participants) who were assigned to study treatment.
Arm/Group Title AIN457 10mg/kg - 75 mg AIN457 10mg/kg - 150 mg Placebo Abatacept Placebo Non-responder - AIN457 75 mg Placebo Non-responder - AIN457 150 mg Placebo Responder - AIN457 75mg Placebo Responder - AIN457 150mg Abatacept Responders Abatacept Non-respnders - AIN457 75mg Abatacept Non-responders - AIN457 150mg
Hide Arm/Group Description:
Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.
Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.
Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.
Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).
Participants switched from placebo to AIN457 75 mg starting at week 16.
Participants switched from placebo to AIN457 150 mg starting at week 16.
Participants switched from placebo to AIN457 75 mg starting at week 24.
Participants switched from placebo to AIN457 150 mg starting at week 24.
Abatacept responders remained on abatacept (from 500 to 1000 mg iv based on weight).
Participants switched from abatacept to AIN457 75 mg starting at week 24.
Participants switched from abatacept to AIN457 150 mg starting at week 24.
Overall Number of Participants Analyzed 138 137 138 138 39 39 23 22 101 18 19
Measure Type: Number
Unit of Measure: Percentage of participants
ACR20,wk 1,n=132,129,130,130,39,35,21,22,96,17,17 22.7 18.6 7.7 11.5 5.1 5.7 14.3 13.6 14.6 0.0 5.9
ACR20,wk 2,n=131,130,134,134,39,36,23,22,99,17,18 26.7 22.3 12.7 25.4 2.6 11.1 34.8 13.6 29.3 11.8 16.7
ACR20,wk 4,n=133,132,131,129,39,39,23,21,93,17,19 36.1 28.0 22.9 34.1 15.4 12.8 43.5 42.9 41.9 17.6 10.5
ACR20,wk 8,n=132,127,131,131,39,39,23,22,95,17,19 38.6 44.9 22.1 52.7 17.9 12.8 39.1 31.8 61.1 29.4 31.6
ACR20,wk 12,n=130,115,123,129,39,37,23,21,94,17,18 30.8 40.0 27.6 51.2 15.4 16.2 47.8 52.4 62.8 17.6 22.2
ACR20,wk 16,n=126,118,116,129,36,37,21,22,94,16,19 38.1 45.8 27.6 55.8 2.8 2.7 76.2 63.6 76.6 0.0 0.0
ACR20,wk 20,n=122,114,119,126,38,37,23,21,91,16,19 39.3 51.8 42.9 57.9 42.1 29.7 60.9 47.6 73.6 6.3 26.3
ACR20,wk 24,n=117,110,117,121,38,36,21,22,87,16,18 45.3 48.2 40.2 57.9 26.3 33.3 57.1 59.1 69.0 31.3 27.8
ACR20,wk28,n=115,103,na,na,33,35,21,21,86,17,19 47.8 65.0 NA [1]  NA [1]  33.3 37.1 71.4 90.5 74.4 41.2 42.1
ACR20,wk32,n=104,97,na,na,33,30,21,19,87,17,17 56.7 61.9 NA [1]  NA [1]  51.5 36.7 81.0 68.4 74.7 23.5 47.1
ACR20,wk36,n=102,93,na,na,30,30,21,20,85,18,16 56.9 53.8 NA [1]  NA [1]  46.7 56.7 85.7 65.0 77.6 27.8 56.3
ACR20,wk40,n=96,90,na,na,28,28,21,19,85,15,17 53.1 61.1 NA [1]  NA [1]  53.6 53.6 85.7 73.7 71.8 40.0 58.8
ACR20,wk44,n=97,90,na,na,28,27,20,18,84,15,16 56.7 61.1 NA [1]  NA [1]  50.0 55.6 85.0 77.8 77.4 33.3 31.3
ACR20,wk48,n=94,89,na,na,28,26,18,19,77,12,14 57.4 68.5 NA [1]  NA [1]  53.6 61.5 72.2 57.9 71.4 25.0 50.0
ACR20,wk52,n=92,88,na,na,28,26,20,18,79,15,15 56.5 62.5 NA [1]  NA [1]  39.3 57.7 75.0 88.9 74.7 40.0 33.3
ACR50,wk1,n=132,129,130,130,39,35,21,22,96,17,17 6.8 3.1 0.8 1.5 0.0 0.0 4.8 0.0 1.0 0.0 5.9
ACR50,wk2,n=131,130,134,134,39,36,23,22,99,17,18 5.3 9.2 3.0 3.0 0.0 0.0 13.0 4.5 3.0 0.0 5.6
ACR50,wk4,n=133,132,131,129,39,39,23,21,93,17,19 9.8 10.6 3.1 7.8 0.0 0.0 8.7 9.5 10.8 0.0 0.0
ACR50,wk8,n=132,127,131,131,39,39,23,22,95,17,19 9.1 16.5 10.7 20.6 5.1 5.1 34.8 9.1 25.3 11.8 5.3
ACR50,wk12,n=130,115,123,129,39,37,23,21,94,17,18 10.0 15.7 11.4 24.8 2.6 8.1 21.7 23.8 30.9 5.9 11.1
ACR50,wk16,n=126,118,116,129,36,37,21,22,94,16,19 15.9 23.7 11.2 26.4 0.0 0.0 38.1 22.7 36.2 0.0 0.0
ACR50,wk20,n=122,114,119,126,38,37,23,21,91,16,19 15.6 21.9 12.6 31.7 7.9 2.7 34.8 14.3 40.7 0.0 15.8
ACR50,wk24,n=117,110,117,121,38,36,21,22,87,16,18 14.5 22.7 14.5 33.1 0.0 11.1 38.1 22.7 44.8 0.0 5.6
ACR50,wk28,n=115,103,na,na,33,35,21,21,86,17,19 13.9 31.1 NA [1]  NA [1]  6.1 8.6 33.3 33.3 41.9 23.5 0.0
ACR50,wk32,n=104,97,na,na,33,30,21,19,87,17,17 21.2 32.0 NA [1]  NA [1]  6.1 13.3 42.9 31.6 47.1 5.9 0.0
ACR50,wk36,n=102,93,na,na,30,30,21,20,85,18,16 23.5 24.7 NA [1]  NA [1]  16.7 16.7 28.6 20.0 47.1 16.7 18.8
ACR50,wk40,n=96,90,na,na,28,28,21,19,85,15,17 25.0 25.6 NA [1]  NA [1]  14.3 28.6 38.1 26.3 45.9 20.0 5.9
ACR50,wk44,n=97,90,na,na,28,27,20,18,84,15,16 27.8 30.0 NA [1]  NA [1]  7.1 29.6 35.0 33.3 50.0 13.3 6.3
ACR50,wk48,n=94,89,na,na,28,26,18,19,77,12,14 25.5 42.7 NA [1]  NA [1]  14.3 23.1 38.9 26.3 48.1 0.0 0.0
ACR50,wk52,n=92,88,na,na,28,26,20,18,79,15,15 26.1 45.5 NA [1]  NA [1]  10.7 26.9 40.0 44.4 51.9 20.0 13.3
ACR70,wk1,n=132,129,130,130,39,35,21,22,96,17,17 0.8 0.8 0.0 0.8 0.0 0.0 0.0 0.0 1.0 0.0 0.0
ACR70,wk2,n=131,130,134,134,39,36,23,22,99,17,18 1.5 0.8 1.5 0.7 0.0 0.0 4.3 4.5 1.0 0.0 0.0
ACR70,wk4,n=133,132,131,129,39,39,23,21,93,17,19 4.5 3.0 1.5 1.6 0.0 0.0 4.3 4.8 2.2 0.0 0.0
ACR70,wk8,n=132,127,131,131,39,39,23,22,95,17,19 1.5 4.7 3.1 6.1 0.0 2.6 13.0 0.0 7.4 5.9 0.0
ACR70,wk12,n=130,115,123,129,39,37,23,21,94,17,18 3.1 3.5 3.3 10.9 0.0 0.0 13.0 4.8 14.9 0.0 0.0
ACR70,wk16,n=126,118,116,129,36,37,21,22,94,16,19 6.3 9.3 3.4 10.0 0.0 0.0 14.3 4.5 13.8 0.0 0.0
ACR70,wk20,n=122,114,119,126,38,37,23,21,91,16,19 6.6 8.8 6.7 11.1 0.0 0.0 21.7 14.3 15.4 0.0 0.0
ACR70,wk24,n=117,110,117,121,38,36,21,22,87,16,18 6.0 12.7 8.5 14.9 0.0 8.3 23.8 9.1 19.5 0.0 5.6
ACR70,wk28,n=115,103,na,na,33,35,21,21,86,17,19 6.1 17.5 NA [1]  NA [1]  0.0 2.9 14.3 14.3 17.4 5.9 0.0
ACR70,wk32,n=104,97,na,na,33,30,21,19,87,17,17 4.8 10.0 NA [1]  NA [1]  0.0 3.3 19.0 0.0 21.8 0.0 0.0
ACR70,wk36,n=102,93,na,na,30,30,21,20,85,18,16 5.9 11.8 NA [1]  NA [1]  3.3 0.0 23.8 0.0 23.5 11.1 0.0
ACR70,wk40,n=96,90,na,na,28,28,21,19,85,15,17 8.3 11.1 NA [1]  NA [1]  7.1 10.7 19.0 10.5 21.2 13.3 0.0
ACR70,wk44,n=97,90,na,na,28,27,20,18,84,15,16 12.4 18.9 NA [1]  NA [1]  0.0 11.1 25.0 11.1 26.2 6.7 0.0
ACR70,wk48,n=94,89,na,na,28,26,18,19,77,12,14 9.6 20.2 NA [1]  NA [1]  3.6 15.4 33.3 10.5 27.3 0.0 0.0
ACR70,wk52,n=92,88,na,na,28,26,20,18,79,15,15 6.5 19.3 NA [1]  NA [1]  0.0 7.7 30.0 16.7 22.8 13.3 0.0
[1]
After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.
7.Secondary Outcome
Title Change From Baseline in HAQ-DI - Using Mixed Model Repeated Measures (MMRM)
Hide Description The HAQ-DI, assesses a subject's level of functional ability and includes questions of fine movements of the upper extremity, locomotor activities of the lower extremity, and activities that involve both upper and lower extremities. There are 20 questions in 8 categories of functioning including dressing, rising, eating, walking, hygiene, reach, grip and usual activities. The stem of each item asks 'Over the past week, "are you able to..." perform a particular task'. Each item is scored on a 4 point scale from 0 - 3, representing normal, no difficulty (0), some difficulty (1), much difficulty (2) and unable to do (3). The disability index score is calculated as the mean of the available category scores, ranging from 0 to 3. A negative change from baseline indicates improvement.
Time Frame baseline, weeks 1, 2, 4, 8, 12, 16, 20 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the full analysis set were considered for this analysis. For Placebo and Abatacept participants, data collected after treatment switch was treated as missing, as were missing values for all treatment groups.
Arm/Group Title AIN457 10mg/kg - 75 mg AIN457 10mg/kg - 150 mg Placebo Abatacept
Hide Arm/Group Description:
Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.
Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.
Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.
Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).
Overall Number of Participants Analyzed 138 137 138 138
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
week 1, n=132,129,130,129 -0.22  (0.032) -0.21  (0.032) -0.08  (0.032) -0.19  (0.032)
week 2, n=131,130,134,133 -0.22  (0.036) -0.25  (0.036) -0.16  (0.036) -0.26  (0.036)
week 4, n=133,133,131,130 -0.30  (0.039) -0.31  (0.040) -0.17  (0.040) -0.36  (0.040)
week 8, n=132,127,131,130 -0.29  (0.042) -0.32  (0.043) -0.17  (0.043) -0.46  (0.043)
week 12, n=130,114,123,129 -0.31  (0.046) -0.33  (0.047) -0.18  (0.047) -0.51  (0.046)
week 16, n=127,118,116,129 -0.30  (0.048) -0.37  (0.049) -0.22  (0.049) -0.52  (0.048)
week 20, n=122,114,47,92 -0.36  (0.051) -0.42  (0.052) -0.21  (0.066) -0.57  (0.054)
week 24, n=117,110,44,86 -0.30  (0.049) -0.39  (0.051) -0.26  (0.065) -0.61  (0.053)
8.Secondary Outcome
Title Change From Baseline in HAQ-DI - Observed Data
Hide Description The HAQ-DI assesses a subject's level of functional ability and includes questions of fine movements of the upper extremity, locomotor activities of the lower extremity, and activities that involve both upper and lower extremities. There are 20 questions in 8 categories of functioning including dressing, rising, eating, walking, hygiene, reach, grip and usual activities. The stem of each item asks 'Over the past week, "are you able to..." perform a particular task'. Each item is scored on a 4 point scale from 0 - 3, representing normal, no difficulty (0), some difficulty (1), much difficulty (2) and unable to do (3). The disability index score is calculated as the mean of the available category scores, ranging from 0 to 3. A negative change from baseline indicates improvement. The HAQ-DI results from baseline up to week 52 were based on observed data, i.e. without imputation.
Time Frame baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the full analysis set were considered for the analysis. Participants with measurements at both baseline and each post-baseline time point were analyzed for that post-baseline time point. The full analysis set was comprised of all randomized participants (excluding mis-randomized participants) who were assigned to study treatment.
Arm/Group Title AIN457 10mg/kg - 75 mg AIN457 10mg/kg - 150 mg Placebo Abatacept Placebo Non-responder - AIN457 75mg Placebo Non-responder - AIN457 150mg Placebo Responder - AIN457 75mg Placebo Responder - AIN457 150mg Abatacept Responders Abatacept Non-responders - AIN457 75mg Abatacept Non-responders - AIN457 150mg
Hide Arm/Group Description:
Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.
Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.
Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.
Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).
Participants switched from placebo to AIN457 75 mg starting at week 16.
Participants switched from placebo to AIN457 150 mg starting at week 16.
Participants switched from placebo to AIN457 75 mg starting at week 24.
Participants switched from placebo to AIN457 150 mg starting at week 24.
Abatacept responders remained on abatacept (from 500 to 1000 mg iv based on weight).
Participants switched from placebo to AIN457 75 mg starting at week 24.
Participants switched from abatacept to AIN457 150 mg starting at week 24.
Overall Number of Participants Analyzed 138 137 138 138 39 39 23 22 101 18 19
Mean (Standard Deviation)
Unit of Measure: score on a scale
wk1,n=132,129,130,129,39,35,21,22,95,17,17 -0.225  (0.3766) -0.215  (0.4095) -0.101  (0.3186) -0.194  (0.4290) -0.119  (0.2896) -0.079  (0.3093) -0.125  (0.4257) -0.153  (0.2468) -0.232  (0.4551) -0.081  (0.3616) -0.096  (0.3047)
Wk2,n=131,130,134,133,39,36,23,22,133,98,17,18 -0.215  (0.3877) -0.239  (0.4885) -0.191  (0.4340) -0.254  (0.4520) -0.122  (0.2605) -0.176  (0.4631) -0.380  (0.5063) -0.250  (0.5015) -0.300  (0.4693) -0.132  (0.3630) -0.118  (0.3987)
Wk4,n=133,133,131,130,39,39,23,21,94,17,19 -0.299  (0.4551) -0.300  (0.5184) -0.214  (0.4492) -0.368  (0.5130) -0.077  (0.3634) -0.224  (0.4968) -0.364  (0.5627) -0.310  (0.3103) -0.445  (0.5245) -0.110  (0.3505) -0.217  (0.4874)
Wk8,n=132,127,131,130,39,39,23,22,94,17,19 -0.277  (0.5062) -0.309  (0.5175) -0.217  (0.5457) -0.463  (0.5182) -0.186  (0.5097) -0.128  (0.5077) -0.543  (0.6313) -0.176  (0.4782) -0.543  (0.5289) -0.206  (0.4900) -0.303  (0.3780)
wk12,n=130,114,123,129,39,37,23,21,94,17,18 -0.287  (0.5384) -0.307  (0.5488) -0.241  (0.5152) -0.508  (0.6369) -0.109  (0.4783) -0.179  (0.5133) -0.451  (0.6167) -0.381  (0.3982) -0.622  (0.6520) -0.221  (0.4274) -0.181  (0.5376)
Wk16,n=127,118,116,129,36,37,21,22,94,16,19 -0.294  (0.5236) -0.355  (0.6217) -0.279  (0.5493) -0.535  (0.6418) -0.167  (0.5295) -0.111  (0.4591) -0.565  (0.5356) -0.472  (0.5988) -0.660  (0.6590) -0.195  (0.4281) -0.204  (0.4827)
Wk20,n=122,114,119,125,38,37,23,21,90,16,19 -0.333  (0.5111) -0.402  (0.6429) -0.319  (0.5637) -0.583  (0.6654) -0.237  (0.4756) -0.179  (0.5158) -0.543  (0.5325) -0.470  (0.7309) -0.699  (0.6849) -0.086  (0.3972) -0.454  (0.5436)
Wk24,n=117,110,117,120,38,36,21,22,86,16,18 -0.268  (0.4930) -0.405  (0.5767) 0.346  (0.5941) -0.590  (0.6872) -0.257  (0.4730) -0.253  (0.6502) -0.589  (0.5648) -0.420  (0.6732) -0.744  (0.6787) -0.180  (0.4257) -0.215  (0.6443)
Wk28,n=115,102,na,na,33,35,21,21,86,17,19 -0.304  (0.5342) -0.439  (0.5780) NA [1]   (NA) NA [1]   (NA) -0.345  (0.5880) -0.336  (0.5846) -0.625  (0.4809) -0.601  (0.5571) -0.689  (0.6428) -0.309  (0.5522) -0.303  (0.5882)
Wk32,n=104,97,na,na,33,30,21,19,87,17,17 -0.358  (0.4964) -0.505  (0.5759) NA [1]   (NA) NA [1]   (NA) -0.284  (0.4627) -0.300  (0.5039) -0.679  (0.5414) -0.546  (0.5998) -0.741  (0.6909) -0.228  (0.5612) -0.375  (0.7315)
Wk36,n=102,93,na,na,30,30,21,19,84,18,16, -0.339  (0.5687) -0.430  (0.5573) NA [1]   (NA) NA [1]   (NA) -0.368  (0.5397) -0.383  (0.4500) -0.607  (0.5538) -0.474  (0.6032) -0.756  (0.6844) -0.285  (0.5891) -0.430  (0.6723)
Wk40,n=96,89,na,na,28,28,21,19,84,15,17 -0.424  (0.5967) -0.440  (0.5416) NA [1]   (NA) NA [1]   (NA) -0.522  (0.6805) -0.391  (0.5446) -0.571  (0.5736) -0.539  (0.6998) -0.763  (0.6750) -0.242  (0.6312) -0.390  (0.6523)
Wk44,n=97,90,na,na,28,27,20,18,84,15,16 -0.331  (0.5871) -0.449  (0.5427) NA [1]   (NA) NA [1]   (NA) -0.277  (0.6377) -0.523  (0.6587) -0.638  (0.5144) -0.514  (0.7752) -0.781  (0.7252) -0.308  (0.6319) -0.203  (0.7917)
Wk48,n-94,89,na,na,28,26,19,19,76,12,14 -0.303  (0.5062) -0.483  (0.5459) NA [1]   (NA) NA [1]   (NA) -0.348  (0.5886) -0.413  (0.5698) -0.605  (0.6113) -0.454  (0.5547) -0.798  (0.6481) -0.229  (0.6546) -0.286  (0.7618)
Wk52,n=92,87,na,na,28,26,20,18,79,15,15 -0.341  (0.5428) -0.516  (0.6036) NA [1]   (NA) NA [1]   (NA) -0.402  (0.5436) -0.351  (0.6335) -0.606  (0.6492) -0.569  (0.7126) -0.788  (0.6853) -0.392  (0.5216) -0.258  (0.8298)
[1]
After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.
9.Secondary Outcome
Title Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Using MMRM
Hide Description The DAS28 is a measure of disease activity in RA based on Swollen and Tender Joint Counts (out of a total of 28), hsCRP and the Patient’s Global Assessment of Disease Activity. A DAS28 score greater than 5.1 implies active disease, equal to or less than 3.2 low disease activity, and less than 2.6 remission. A negative change from baseline indicates improvement.
Time Frame baseline, weeks 1, 2, 4, 8, 12, 16, 20 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the full analysis set were considered for the analysis. For Placebo and Abatacept participants, data collected after treatment switch was treated as missing, as were missing values for all treatment groups
Arm/Group Title AIN457 10mg/kg - 75 mg AIN457 10mg/kg - 150 mg Placebo Abatacept
Hide Arm/Group Description:
Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.
Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.
Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.
Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).
Overall Number of Participants Analyzed 138 137 138 39
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
week 1, n=131,129,130,129 -0.89  (0.069) -0.73  (0.069) -0.22  (0.069) -0.50  (0.069)
week 2, n=131,127,132,133 -0.96  (0.080) -0.90  (0.081) -0.35  (0.080) -0.78  (0.080)
week 4, n=130,131,138,138 -1.20  (0.090) -1.11  (0.090) -0.48  (0.090) -1.11  (0.091)
week 8, n=130,126,130,130 -1.21  (0.093) -1.23  (0.094) -0.61  (0.093) -1.55  (0.093)
week 12, n=130,114,123,128 -1.23  (0.097) -1.36  (0.102) -0.73  (0.100) -1.78  (0.098)
week 16, n=126,116,114,127 -1.23  (0.108) -1.40  (0.112) -0.57  (0.112) -1.71  (0.108)
week 20, n=121,114,47,92 -1.44  (0.108) -1.49  (0.111) -0.89  (0.146) -1.96  (0.117)
week 24, n=116,108,44,84 -1.47  (0.115) -1.47  (0.119) -1.02  (0.163) -2.07  (0.128)
10.Secondary Outcome
Title Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Observed Data
Hide Description The DAS28 is a measure of disease activity in RA based on Swollen and Tender Joint Counts (out of a total of 28), hsCRP and the Patient’s Global Assessment of Disease Activity. A DAS28 score greater than 5.1 implies active disease, equal to or less than 3.2 low disease activity, and less than 2.6 remission. A negative change from baseline indicates improvement. The DAS28-CRP results from baseline up to week 52 were based on observed data, i.e. without imputation.
Time Frame baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the full analysis set were considered for the analysis. Participants with measurements at both baseline and each post-baseline time point were analyzed for that post-baseline time point. The full analysis set was comprised of all randomized participants (excluding mis-randomized participants) who were assigned to study treatment.
Arm/Group Title AIN457 10mg/kg - 75 mg AIN457 10mg/kg - 150 mg Placebo Abatacept Placebo Non-responder - AIN457 75mg Placebo Non-responder - AIN457 150mg Placebo Responder - AIN457 75mg Placebo Responder - AIN457 150mg Abatacept Responders Abatacept Non-responders - AIN457 75mg Abatacept Non-responders - AIN457 150mg
Hide Arm/Group Description:
Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.
Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.
Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.
Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).
Participants switched from placebo to AIN457 75 mg starting at week 16.
Participants switched from placebo to AIN457 150 mg starting at week 16.
Participants switched from placebo to AIN457 75 mg starting at week 24.
Participants switched from placebo to AIN457 150 mg starting at week 24.
Abatacept responders remained on abatacept (from 500 to 1000 mg iv based on weight).
Participants switched from placebo to AIN457 75 mg starting at week 24.
Participants switched from abatacept to AIN457 150 mg starting at week 24.
Overall Number of Participants Analyzed 138 137 138 39 39 23 22 138 101 18 19
Mean (Standard Deviation)
Unit of Measure: score on a scale
Wk1,n=131,129,130,129,39,35,21,22, 95,17,17 -0.886  (0.9784) -0.759  (0.8654) -0.211  (0.6877) -0.502  (0.7539) -0.147  (0.5527) -0.141  (0.7095) -0.572  (0.7856) -0.235  (0.7699) -0.577  (0.7924) -0.361  (0.3578) -0.222  (0.7695)
Wk2,n=131,127,132,133,39,36,23,21,98,17,18 -0.909  (1.0331) -0.900  (1.0284) -0.363  (0.8388) -0.755  (0.9234) -0.191  (0.7331) -0.368  (0.7170) -0.835  (0.9466) -0.292  (0.7448) -0.755  (0.9234) -0.882  (0.9526) -0.359  (0.8980)
Wk4,n=130,131,129,128,39,38,23,21,92,17,19 -1.163  (1.1656) -1.150  (1.1942) -0.492  (0.8876) -1.095  (1.0483) -0.252  (0.8116) -0.352  (0.7471) -1.034  (0.9119) -0.767  (0.9661) -1.268  (1.0533) -0.595  (1.1160) -0.706  (0.6999)
Wk8,n=130,126,130,130,39,39,23,22,94,17,19 -1.181  (1.1821) -1.283  (1.1678) -0.644  (1.1356) -1.541  (1.1172) -0.546  (1.1597) -0.312  (0.9151) -1.403  (1.2060) -0.613  (0.9772) -1.816  (1.0708) -0.834  (1.1469) -0.808  (0.6444)
Wk12,n=130,114,123,128,39,37,23,21,93,17,18 -1.229  (1.1782) -1.402  (1.2182) -0.742  (1.2330) -1.790  (1.2356) -0.311  (0.9514) -0.383  (1.1765) -1.588  (0.9714) -1.330  (1.4721) -2.144  (1.1028) -0.749  (1.0757) -0.945  (1.1008)
Wk16,n=126,116,114,128,36,36,21,21,94,15,19 -1.225  (1.2866) -1.455  (1.3489) -0.592  (1.2557) -1.691  (1.2979) 0.128  (0.8579) 0.045  (0.9145) -2.008  (0.8675) -1.503  (0.8746) -2.159  (1.0767) -0.490  (0.8170) -0.322  (1.0262)
Wk20,n=121,114,,119,125,38,37,23,21,90,16,19 -1.427  (1.3266) -1.569  (1.2361) -1.164  (1.2087) -1.840  (1.4144) -0.683  (1.1231) -0.937  (1.0966) -2.108  (1.0368) -1.399  (1.1487) -2.317  (1.2549) -0.402  (0.9820) -0.792  (1.0272)
Wk24,n=116,108,116,117,37,36,21,22,84,15,18 -1.467  (1.3116) -1.579  (1.3221) -1.248  (1.2915) -1.989  (1.4717) -0.666  (0.9983) -1.140  (1.1954) -2.343  (1.2649) -1.362  (1.2999) -2.435  (1.3266) -0.772  (1.1656) -0.923  (1.2560)
Wk28,n=115,103,na,na,33,35,21,21,86,17,18 -1.484  (1.3216) -1.819  (1.3434) NA [1]   (NA) NA [1]   (NA) -1.172  (1.1602) -1.244  (1.2433) -2.117  (0.8573) -1.782  (1.0655) -2.470  (1.2153) -1.137  (1.2050) -0.973  (1.1034)
Wk32,n=103,97,na,na,33,39,23,22,87,17,16 -1.738  (1.2783) -1.966  (1.1770) NA [1]   (NA) NA [1]   (NA) -1.408  (1.3855) -1.475  (1.1846) -2.363  (1.0711) -1.875  (0.9807) -2.629  (1.3104) -0.961  (1.0043) -1.464  (1.2025)
Wk36,n=101,92,na,na,30,30,21,20,84,18,15 -1.737  (1.4592) -1.820  (1.2500) NA [1]   (NA) NA [1]   (NA) -1.271  (1.4949) -1.444  (1.1949) -2.269  (1.0688) -1.784  (0.9029) -2.642  (1.4305) -1.200  (1.3228) -1.425  (0.9247)
Wk40,n=96,90,na,na,28,28,21,19,84,15,17 -1.742  (1.3259) -1.788  (1.1333) NA [1]   (NA) NA [1]   (NA) -1.354  (1.3590) -1.494  (1.3243) -2.315  (1.0773) -2.134  (1.0405) -2.549  (1.3305) -1.201  (1.5293) -1.612  (1.1839)
Wk44,n=96,88,na,na,28,27,20,18,84,15,16 -1.764  (1.3227) -1.932  (1.2850) NA [1]   (NA) NA [1]   (NA) -1.168  (1.2638) -1.858  (1.2373) -2.155  (0.9488) -2.121  (1.1347) -2.697  (1.2117) -0.881  (1.3337) -1.528  (1.2973)
Wk48,n=94,88,na,na,28,26,18,19,76,12,14 -1.761  (1.3152) -2.200  (1.3293) NA [1]   (NA) NA [1]   (NA) -1.516  (1.0635) -1.660  (1.1805) -2.259  (1.1813) -1.964  (1.3404) -2.634  (1.2189) -1.013  (1.1738) -1.400  (1.1985)
Wk52,n=92,86,na,na,28,26,20,18,79,15,15 -1.839  (1.3755) -2.109  (1.4000) NA [1]   (NA) NA [1]   (NA) -1.487  (1.0729) -1.690  (1.2093) -2.070  (0.9984) -2.334  (1.1428) -2.676  (1.3593) -1.390  (1.1884) -0.982  (1.1943)
[1]
After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.
11.Secondary Outcome
Title Change From Baseline in hsCRP - Observed Data
Hide Description Blood samples were obtained to identify the presence of inflammation, to determine its severity and to monitor response to treatment. A negative change from baseline indicates improvement. The hsCRP results from baseline up to week 52 were based on observed data, i.e. without imputation.
Time Frame baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the full analysis set were considered for the analysis. Participants with measurements at both baseline and each post-baseline time point were analyzed for that post-baseline time point. The full analysis set was comprised of all randomized participants (excluding mis-randomized participants) who were assigned to study treatment.
Arm/Group Title AIN457 10mg/kg - 75 mg AIN457 10mg/kg - 150 mg Placebo Abatacept Placebo Non-responder - AIN457 75mg Placebo Non-responder - AIN457 150mg Placebo Responder - AIN457 75mg Placebo Responder - AIN457 150mg Abatacept Responders Abatacept Non-responders - AIN457 75mg Abatacept Non-responders - AIN457 150mg
Hide Arm/Group Description:
Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.
Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.
Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.
Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).
Participants switched from placebo to AIN457 75 mg starting at week 16.
Participants switched from placebo to AIN457 150 mg starting at week 16.
Participants switched from placebo to AIN457 75 mg starting at week 24.
Participants switched from placebo to AIN457 150 mg starting at week 24.
Abatacept responders remained on abatacept (from 500 to 1000 mg iv based on weight).
Participants switched from placebo to AIN457 75 mg starting at week 24.
Participants switched from abatacept to AIN457 150 mg starting at week 24.
Overall Number of Participants Analyzed 138 137 138 138 39 39 23 22 101 18 19
Mean (Standard Deviation)
Unit of Measure: mg/L
Wk1,n=134,130,131,131,39,36,21,22,97,17,17 -10.91  (30.815) -10.31  (27.754) -0.69  (15.521) -5.64  (18.550) -0.33  (10.430) -0.84  (24.777) -0.40  (12.244) -1.50  (7.541) -6.40  (20.458) -2.92  (12.405) -4.07  (10.811)
Wk2,n=133,129,133,135,39,36,23,21,100,17,18 -10.24  (33.209) -11.51  (32.139) -2.21  (14.501) -6.36  (19.416) 0.43  (15.333) -5.48  (17.301) -1.70  (11.170) -4.78  (10.515) -7.52  (20.301) -3.84  (13.737) -2.30  (19.035)
Wk4,n=131,134,129,133,39,38,23,21,97,17,19 -9.10  (20.514) -10.76  (33.376) -1.53  (19.311) -6.70  (20.732) 2.23  (23.317) -1.94  (21.927) -6.47  (12.458) -1.95  (12.090) -7.53  (22.982) -4.42  (14.991) -4.50  (11.029)
Wk8,n=134,128,130,132,39,39,23,22,96,17,19 -10.18  (33.400) -12.94  (30.854) -2.94  (20.601) -8.48  (21.134) -4.72  (18.766) -3.28  (25.501) 0.13  (18.061) -1.50  (12.839) -10.13  (22.724) -.54  (14.849) -4.59  (16.603)
Wk12,n=133,119,128,131,39,39,23,22,96,17,18 -9.41  (31.859) -9.66  (24.298) -0.69  (18.908) -9.72  (25.787) 2.11  (18.312) -2.89  (20.763) -2.74  (12.899) 2.10  (22.545) -12.17  (25.813) -4.18  (16.024) -1.94  (31.483)
Wk16,n=129,120,121,131,36,38,21,21,96,16,19 -9.97  (33.291) -5.78  (25.418) -1.82  (20.849) -8.37  (22.571) 3.92  (23.403) -2.13  (24.422) -5.67  (9.583) -4.29  (13.497) -11.25  (23.692) -1.41  (8.810) 0.32  (22.024)
Wk20,n=124,116,120,127,38,37,23,21,91,17,19 -9.19  (32.876) -8.05  (22.394) -3.75  (29.301) -9.43  (23.212) -5.33  (20.645) -7.77  (27.581) 3.23  (48.634) -1.06  (15.737) -11.59  (24.271) -3.94  (15.716) -3.99  (32.871)
Wk24,n=121,113,116,120,37,36,21,22,86,16,18 -6.90  (22.098) -4.92  (23.075) -6.88  (21.014) -8.66  (21.574) -7.06  (20.298) -11.46  (26.373) -6.40  (11.562) 0.45  (18.244) -11.72  (22.198) -4.94  (13.605) 2.63  (20.875)
Wk28,n=119,110,na,na,34,35,21,21,89,17,18 -4.94  (23.155) -5.87  (25.885) NA [1]   (NA) NA [1]   (NA) -4.43  (21.777) -11.10  (27.186) -7.97  (18.018) 0.09  (24.933) -12.08  (22.791) -4.51  (14.144) -1.70  (22.671)
Wk32,n=107,101,na,na,34,32,20,21,87,17,16 -8.57  (20.826) 7.37  (24.564) NA [1]   (NA) NA [1]   (NA) -4.34  (23.742) -9.08  (25.867) -5.02  (10.300) -5.51  (14.279) -12.83  (23.330) -4.26  (15.329) -7.14  (17.446)
Wk36,n=107,98,na,na,32,31,21,20,85,18,15 -6.60  (25.895) -6.36  (22.571) NA [1]   (NA) NA [1]   (NA) -4.21  (27.424) -2.35  (37.226) -2.73  (21.272) -6.78  (13.940) -12.19  (24.535) -4.38  (14.479) -0.47  (27.932)
WK40,n=101,96,na,na,29,29,22,20,86,15,17 -8.74  (22.257) -7.09  (24.325) NA [1]   (NA) NA [1]   (NA) -7.07  (26.156) 2.39  (32.966) -4.46  (22.808) -4.73  (13.502) -12.63  (23.788) -2.75  (17.297) -7.95  (18.343)
Wk44,n=97,92,na,na,,28,28,20,19,85,15,16 -6.59  (20.975) -7.25  (24.681) NA [1]   (NA) NA [1]   (NA) -6.66  (23.396) -8.53  (19.970) -6.50  (19.968) -7.27  (13.887) -12.32  (25.470) -1.33  (4.846) -3.69  (24.389)
Wk48,n=97,91,na,na,28,29,20,19,79,13,14 -6.19  (18.912) -7.63  (21.682) NA [1]   (NA) NA [1]   (NA) -10.49  (25.564) -4.76  (15.784) -1.43  (33.122) -6.97  (13.680) -13.90  (25.636) -3.50  (21.343) -4.48  (16.918)
Wk52,n=95,92,na,na,29,28,20,18,83,16,16 -6.68  (26.240) -8.14  (22.149) NA [1]   (NA) NA [1]   (NA) -4.63  (25.795) -4.79  (22.882) 2.95  (9.880) -4.88  (11.707) -11.19  (27.768) -6.73  (14.972) -5.78  (18.534)
[1]
After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.
12.Secondary Outcome
Title Change From Baseline in Erythrocyte Sedimentation Rate (ESR) - Observed Data
Hide Description Blood samples were obtained to monitor disease activity and response to treatment. A negative change from baseline indicates improvement. The ESR results from baseline up to week 52 were based on observed data, i.e. without imputation.
Time Frame baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the full analysis set were considered for the analysis. Participants with measurements at both baseline and each post-baseline time point were analyzed for that post-baseline time point. The full analysis set was comprised of all randomized participants (excluding mis-randomized participants) who were assigned to study treatment.
Arm/Group Title AIN457 10mg/kg - 75 mg AIN457 10mg/kg - 150 mg Placebo Abatacept Placebo Non-responder - AIN457 75mg Placebo Non-responder - AIN457 150mg Placebo Responder - AIN457 75mg Placebo Responder - AIN457 150mg Abatacept Responders Abatacept Non-responders - AIN457 75mg Abatacept Non-responders - AIN457 150mg
Hide Arm/Group Description:
Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks.
Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks.
Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.
Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).
Participants switched from placebo to AIN457 75 mg starting at week 16.
Participants switched from placebo to AIN457 150 mg starting at week 16.
Participants switched from placebo to AIN457 75 mg starting at week 24.
Participants switched from placebo to AIN457 150 mg starting at week 24.
Abatacept responders remained on abatacept (from 500 to 1000 mg iv based on weight).
Participants switched from placebo to AIN457 75 mg starting at week 24.
Participants switched from abatacept to AIN457 150 mg starting at week 24.
Overall Number of Participants Analyzed 138 137 138 138 39 39 23 22 101 18 19
Mean (Standard Deviation)
Unit of Measure: mm/hr
Wk1,n=133,130,131,131,39,36,21,22,97,17,17, -7.5  (18.74) -8.4  (19.20) -5.7  (15.68) -9.5  (16.55) -8.4  (12.65) -1.1  (18.88) -5.7  (14.97) -7.1  (13.22) -10.2  (17.11) -7.7  (13.90) -7.2  (16.30)
Wk2,n=133,130,135,134,39,36,23,22,99,17,18 -12.2  (19.06) -10.5  (19.05) -5.7  (18.22) -11.0  (19.50) -4.0  (12.69) -5.6  (26.44) -9.7  (17.86) -6.6  (14.44) -10.2  (20.33) -12.5  (16.71) -13.6  (17.78)
Wk4,n=133,135,131,133,39,39,23,21,97,17,19 -12.7  (22.23) -12.1  (21.88) -6.0  (18.90) -12.6  (18.14) -3.7  (14.35) -3.8  (20.50) -9.3  (13.81) -8.2  (23.89) -12.3  (18.66) -15.8  (17.49) -11.3  (16.46)
Wk8,n=133,129,131,132,39,39,23,22,96,17,19 -15.4  (20.38) -15.7  (21.62) -6.4  (22.72) -17.6  (20.89) -9.4  (19.24) -0.9  (27.25) -8.2  (24.09) -8.3  (14.29) -18.3  (21.56) -13.9  (23.29) -17.6  (15.03)
Wk12,n=133,118,127,131,39,39,23,21,96,17,18 -14.7  (20.08) -18.4  (21.18) -5.8  (21.02) -19.4  (20.97) -5.9  (17.96) -1.5  (25.62) -11.2  (18.06) -5.5  (20.06) -19.9  (21.08) -18.4  (23.07) -17.9  (19.31)
Wk16,n=129,121,122,130,36,38,21,22,95,16,19 -16.2  (21.22) -15.6  (19.09) -6.5  (23.48) -18.5  (24.32) -3.1  (19.21) -1.1  (25.47) -17.6  (23.03) -4.9  (20.54) -21.1  (24.73) -14.9  (17.78) -8.8  (25.22)
Wk20,n=123,116,120,127,38,37,23,21,91,17,19 -16.3  (20.90) -17.7  (19.90) -9.1  (26.29) -21.1  (23.66) -21.1  (23.66) -10.5  (20.08) -7.4  (29.40) -11.6  (34.23) -7.0  (22.32) -22.0  (23.60) -20.5  (22.81)
Wk24,n=122,113,117,123,38,36,21,22,88,17,18 -13.9  (23.65) -16.0  (20.20) -12.0  (24.31) -19.6  (24.52) -10.8  (20.33) -14.7  (27.77) -16.1  (21.57) -5.5  (27.07) -21.1  (24.62) -20.7  (20.65) -11.4  (26.96)
Wk28,n=119,110,na,na,34,35,21,21,89,17,19 -15.4  (22.95) -16.8  (23.05) NA [1]   (NA) NA [1]   (NA) -17.9  (24.87) -12.5  (30.87) -12.3  (24.10) -14.6  (17.31) -22.4  (22.90) -26.1  (19.83) -17.4  (24.77)
Wk32,n=108,101,na,na,34,32,21,21,88,17,16 -18.3  (23.51) -17.4  (21.57) NA [1]   (NA) NA [1]   (NA) -17.2  (16.70) -12.8  (26.21) -16.8  (24.37) -14.1  (20.72) -25.5  (24.89) -25.7  (21.14) -23.1  (21.46)
Wk36,n=107,98,na,na,32,31,21,20,87,18,16 -16.6  (25.20) -18.4  (21.51) NA [1]   (NA) NA [1]   (NA) -17.8  (21.72) -13.4  (29.49) -17.3  (22.02) -16.5  (17.95) -21.7  (25.40) -26.0  (21.21) -16.6  (23.31)
Wk40,n=101,96,na,na,29,29,22,20,85,15,17 -18.1  (21.06) -17.3  (21.05) NA [1]   (NA) NA [1]   (NA) -20.6  (19.66) -12.3  (26.37) -13.3  (18.78) -16.4  (21.79) -22.2  (26.24) -23.8  (22.96) -22.9  (15.57)
Wk44,n=98,93,na,na,28,28,20,19,85,15,16 -18.0  (21.08) -16.7  (23.87) NA [1]   (NA) NA [1]   (NA) -20.1  (17.61) -16.0  (25.30) -12.0  (29.20) -19.2  (22.57) -24.9  (25.66) -22.3  (23.36) -18.5  (21.00)
Wk48,n=97,92,na,na,28,30,20,19,79,13,14 -17.8  (23.11) -19.8  (20.30) NA [1]   (NA) NA [1]   (NA) -20.8  (18.26) -7.2  (22.58) -12.2  (29.55) -19.4  (20.58) -23.9  (25.56) -18.9  (26.41) -20.2  (18.16)
Wk52,n=94,91,na,na,29,28,20,18,83,16,16 -17.7  (21.08) -20.6  (23.48) NA [1]   (NA) NA [1]   (NA) -14.9  (20.53) -15.1  (21.50) -14.4  (24.54) -13.6  (27.16) -25.2  (27.88) -27.4  (22.71) -15.4  (22.53)
[1]
After week 24, placebo and abatacept analysis was done on 'AIN457 switch' groups only.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Any AIN457 75 mg Any AIN457 150 mg Placebo Abatacept
Hide Arm/Group Description Any AIN457 75 mg Any AIN457 150 mg Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24. Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).
All-Cause Mortality
Any AIN457 75 mg Any AIN457 150 mg Placebo Abatacept
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Any AIN457 75 mg Any AIN457 150 mg Placebo Abatacept
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   30/218 (13.76%)   28/215 (13.02%)   7/139 (5.04%)   9/137 (6.57%) 
Blood and lymphatic system disorders         
Thrombocytopenia  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Cardiac disorders         
Angina pectoris  1  0/218 (0.00%)  0/215 (0.00%)  1/139 (0.72%)  0/137 (0.00%) 
Angina unstable  1  0/218 (0.00%)  1/215 (0.47%)  0/139 (0.00%)  0/137 (0.00%) 
Cardiac failure  1  2/218 (0.92%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Mitral valve incompetence  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Palpitations  1  0/218 (0.00%)  1/215 (0.47%)  0/139 (0.00%)  0/137 (0.00%) 
Sinus tachycardia  1  0/218 (0.00%)  0/215 (0.00%)  1/139 (0.72%)  0/137 (0.00%) 
Ear and labyrinth disorders         
Sudden hearing loss  1  0/218 (0.00%)  1/215 (0.47%)  0/139 (0.00%)  0/137 (0.00%) 
Eye disorders         
Cataract  1  0/218 (0.00%)  0/215 (0.00%)  1/139 (0.72%)  0/137 (0.00%) 
Gastrointestinal disorders         
Abdominal pain  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Colitis ischaemic  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Inguinal hernia  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Intestinal polyp  1  0/218 (0.00%)  0/215 (0.00%)  0/139 (0.00%)  1/137 (0.73%) 
Umbilical hernia  1  0/218 (0.00%)  0/215 (0.00%)  0/139 (0.00%)  1/137 (0.73%) 
General disorders         
Cyst  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Death  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Device dislocation  1  0/218 (0.00%)  1/215 (0.47%)  0/139 (0.00%)  0/137 (0.00%) 
General physical health deterioration  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Hepatobiliary disorders         
Bile duct stone  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Cholelithiasis  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Hepatic steatosis  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Liver disorder  1  0/218 (0.00%)  1/215 (0.47%)  0/139 (0.00%)  0/137 (0.00%) 
Infections and infestations         
Cellulitis  1  0/218 (0.00%)  1/215 (0.47%)  0/139 (0.00%)  0/137 (0.00%) 
Diverticulitis  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Escherichia urinary tract infection  1  1/218 (0.46%)  1/215 (0.47%)  0/139 (0.00%)  0/137 (0.00%) 
Eye abscess  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Gastroenteritis  1  0/218 (0.00%)  1/215 (0.47%)  0/139 (0.00%)  0/137 (0.00%) 
Gastroenteritis salmonella  1  0/218 (0.00%)  0/215 (0.00%)  1/139 (0.72%)  0/137 (0.00%) 
H1N1 influenza  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Herpes zoster oticus  1  0/218 (0.00%)  1/215 (0.47%)  0/139 (0.00%)  0/137 (0.00%) 
Joint abscess  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Lower respiratory tract infection  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Meningitis bacterial  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Pneumonia influenzal  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Pyelonephritis acute  1  0/218 (0.00%)  0/215 (0.00%)  0/139 (0.00%)  1/137 (0.73%) 
Sepsis  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Septic shock  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Sinusitis  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Tooth abscess  1  0/218 (0.00%)  1/215 (0.47%)  0/139 (0.00%)  0/137 (0.00%) 
Injury, poisoning and procedural complications         
Contusion  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Laceration  1  0/218 (0.00%)  1/215 (0.47%)  0/139 (0.00%)  0/137 (0.00%) 
Lumbar vertebral fracture  1  0/218 (0.00%)  1/215 (0.47%)  0/139 (0.00%)  0/137 (0.00%) 
Procedural headache  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Spinal fracture  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Upper limb fracture  1  0/218 (0.00%)  1/215 (0.47%)  0/139 (0.00%)  0/137 (0.00%) 
Musculoskeletal and connective tissue disorders         
Acquired claw toe  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Arthritis  1  1/218 (0.46%)  1/215 (0.47%)  0/139 (0.00%)  0/137 (0.00%) 
Back pain  1  2/218 (0.92%)  1/215 (0.47%)  0/139 (0.00%)  0/137 (0.00%) 
Bursitis  1  1/218 (0.46%)  1/215 (0.47%)  1/139 (0.72%)  0/137 (0.00%) 
Foot deformity  1  0/218 (0.00%)  2/215 (0.93%)  0/139 (0.00%)  0/137 (0.00%) 
Intervertebral disc disorder  1  0/218 (0.00%)  1/215 (0.47%)  0/139 (0.00%)  0/137 (0.00%) 
Intervertebral disc protrusion  1  0/218 (0.00%)  2/215 (0.93%)  0/139 (0.00%)  1/137 (0.73%) 
Osteoarthritis  1  4/218 (1.83%)  2/215 (0.93%)  0/139 (0.00%)  0/137 (0.00%) 
Osteoporotic fracture  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  1/137 (0.73%) 
Rheumatoid arthritis  1  0/218 (0.00%)  2/215 (0.93%)  0/139 (0.00%)  0/137 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Breast cancer  1  0/218 (0.00%)  0/215 (0.00%)  0/139 (0.00%)  1/137 (0.73%) 
Fibroadenoma of breast  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Lipoma  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Papillary thyroid cancer  1  1/218 (0.46%)  1/215 (0.47%)  0/139 (0.00%)  0/137 (0.00%) 
Squamous cell carcinoma  1  0/218 (0.00%)  1/215 (0.47%)  0/139 (0.00%)  0/137 (0.00%) 
Nervous system disorders         
Cerebral ischaemia  1  0/218 (0.00%)  0/215 (0.00%)  0/139 (0.00%)  1/137 (0.73%) 
Cerebrospinal fluid leakage  1  0/218 (0.00%)  1/215 (0.47%)  0/139 (0.00%)  0/137 (0.00%) 
Cerebrovascular accident  1  0/218 (0.00%)  1/215 (0.47%)  0/139 (0.00%)  0/137 (0.00%) 
Formication  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Lumbar radiculopathy  1  0/218 (0.00%)  1/215 (0.47%)  0/139 (0.00%)  0/137 (0.00%) 
Meningorrhagia  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Perineurial cyst  1  0/218 (0.00%)  0/215 (0.00%)  1/139 (0.72%)  0/137 (0.00%) 
Syncope  1  0/218 (0.00%)  0/215 (0.00%)  0/139 (0.00%)  1/137 (0.73%) 
Transient ischaemic attack  1  2/218 (0.92%)  1/215 (0.47%)  0/139 (0.00%)  0/137 (0.00%) 
Vertebrobasilar insufficiency  1  0/218 (0.00%)  0/215 (0.00%)  1/139 (0.72%)  0/137 (0.00%) 
Psychiatric disorders         
Delirium  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Depression  1  0/218 (0.00%)  0/215 (0.00%)  1/139 (0.72%)  0/137 (0.00%) 
Renal and urinary disorders         
Acute kidney injury  1  0/218 (0.00%)  1/215 (0.47%)  0/139 (0.00%)  1/137 (0.73%) 
Reproductive system and breast disorders         
Cystocele  1  0/218 (0.00%)  0/215 (0.00%)  0/139 (0.00%)  1/137 (0.73%) 
Metrorrhagia  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Rectocele  1  0/218 (0.00%)  0/215 (0.00%)  0/139 (0.00%)  1/137 (0.73%) 
Respiratory, thoracic and mediastinal disorders         
Acute pulmonary oedema  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Dyspnoea  1  1/218 (0.46%)  1/215 (0.47%)  0/139 (0.00%)  0/137 (0.00%) 
Haemoptysis  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Hypoxia  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Pulmonary embolism  1  0/218 (0.00%)  1/215 (0.47%)  0/139 (0.00%)  0/137 (0.00%) 
Pulmonary hypertension  1  0/218 (0.00%)  0/215 (0.00%)  0/139 (0.00%)  1/137 (0.73%) 
Respiratory failure  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Skin and subcutaneous tissue disorders         
Angioedema  1  0/218 (0.00%)  1/215 (0.47%)  0/139 (0.00%)  0/137 (0.00%) 
Rash  1  0/218 (0.00%)  0/215 (0.00%)  0/139 (0.00%)  1/137 (0.73%) 
Skin ulcer  1  1/218 (0.46%)  1/215 (0.47%)  0/139 (0.00%)  0/137 (0.00%) 
Vascular disorders         
Venous thrombosis limb  1  1/218 (0.46%)  0/215 (0.00%)  0/139 (0.00%)  0/137 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Any AIN457 75 mg Any AIN457 150 mg Placebo Abatacept
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   144/218 (66.06%)   146/215 (67.91%)   51/139 (36.69%)   78/137 (56.93%) 
Blood and lymphatic system disorders         
Anaemia  1  10/218 (4.59%)  10/215 (4.65%)  8/139 (5.76%)  6/137 (4.38%) 
Leukopenia  1  6/218 (2.75%)  4/215 (1.86%)  0/139 (0.00%)  2/137 (1.46%) 
Lymphopenia  1  5/218 (2.29%)  5/215 (2.33%)  4/139 (2.88%)  2/137 (1.46%) 
Neutrophilia  1  2/218 (0.92%)  2/215 (0.93%)  3/139 (2.16%)  1/137 (0.73%) 
Thrombocytopenia  1  1/218 (0.46%)  1/215 (0.47%)  4/139 (2.88%)  1/137 (0.73%) 
Ear and labyrinth disorders         
Vertigo  1  1/218 (0.46%)  5/215 (2.33%)  0/139 (0.00%)  1/137 (0.73%) 
Gastrointestinal disorders         
Diarrhoea  1  16/218 (7.34%)  12/215 (5.58%)  0/139 (0.00%)  9/137 (6.57%) 
Dyspepsia  1  6/218 (2.75%)  3/215 (1.40%)  1/139 (0.72%)  2/137 (1.46%) 
Nausea  1  9/218 (4.13%)  5/215 (2.33%)  2/139 (1.44%)  1/137 (0.73%) 
General disorders         
Oedema peripheral  1  9/218 (4.13%)  6/215 (2.79%)  0/139 (0.00%)  2/137 (1.46%) 
Pyrexia  1  3/218 (1.38%)  9/215 (4.19%)  1/139 (0.72%)  2/137 (1.46%) 
Infections and infestations         
Bronchitis  1  10/218 (4.59%)  12/215 (5.58%)  0/139 (0.00%)  5/137 (3.65%) 
Gastroenteritis  1  8/218 (3.67%)  4/215 (1.86%)  0/139 (0.00%)  5/137 (3.65%) 
Influenza  1  7/218 (3.21%)  13/215 (6.05%)  1/139 (0.72%)  1/137 (0.73%) 
Nasopharyngitis  1  24/218 (11.01%)  17/215 (7.91%)  4/139 (2.88%)  8/137 (5.84%) 
Oral candidiasis  1  1/218 (0.46%)  3/215 (1.40%)  0/139 (0.00%)  4/137 (2.92%) 
Pharyngitis  1  10/218 (4.59%)  5/215 (2.33%)  1/139 (0.72%)  5/137 (3.65%) 
Respiratory tract infection  1  2/218 (0.92%)  5/215 (2.33%)  0/139 (0.00%)  1/137 (0.73%) 
Rhinitis  1  8/218 (3.67%)  12/215 (5.58%)  1/139 (0.72%)  3/137 (2.19%) 
Sinusitis  1  9/218 (4.13%)  7/215 (3.26%)  2/139 (1.44%)  1/137 (0.73%) 
Tonsillitis  1  6/218 (2.75%)  3/215 (1.40%)  0/139 (0.00%)  0/137 (0.00%) 
Tracheobronchitis  1  5/218 (2.29%)  1/215 (0.47%)  1/139 (0.72%)  1/137 (0.73%) 
Upper respiratory tract infection  1  18/218 (8.26%)  21/215 (9.77%)  9/139 (6.47%)  6/137 (4.38%) 
Urinary tract infection  1  16/218 (7.34%)  10/215 (4.65%)  2/139 (1.44%)  8/137 (5.84%) 
Viral infection  1  1/218 (0.46%)  6/215 (2.79%)  0/139 (0.00%)  2/137 (1.46%) 
Injury, poisoning and procedural complications         
Contusion  1  2/218 (0.92%)  5/215 (2.33%)  1/139 (0.72%)  1/137 (0.73%) 
Fall  1  3/218 (1.38%)  7/215 (3.26%)  3/139 (2.16%)  1/137 (0.73%) 
Investigations         
Alanine aminotransferase increased  1  4/218 (1.83%)  3/215 (1.40%)  0/139 (0.00%)  3/137 (2.19%) 
Lipoprotein (a) increased  1  2/218 (0.92%)  6/215 (2.79%)  0/139 (0.00%)  1/137 (0.73%) 
Metabolism and nutrition disorders         
Dyslipidaemia  1  5/218 (2.29%)  3/215 (1.40%)  1/139 (0.72%)  2/137 (1.46%) 
Hypercholesterolaemia  1  7/218 (3.21%)  7/215 (3.26%)  6/139 (4.32%)  10/137 (7.30%) 
Hyperlipidaemia  1  6/218 (2.75%)  11/215 (5.12%)  2/139 (1.44%)  1/137 (0.73%) 
Hypertriglyceridaemia  1  2/218 (0.92%)  2/215 (0.93%)  3/139 (2.16%)  3/137 (2.19%) 
Hypocalcaemia  1  2/218 (0.92%)  3/215 (1.40%)  3/139 (2.16%)  1/137 (0.73%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  17/218 (7.80%)  15/215 (6.98%)  1/139 (0.72%)  5/137 (3.65%) 
Arthritis  1  5/218 (2.29%)  5/215 (2.33%)  2/139 (1.44%)  3/137 (2.19%) 
Back pain  1  12/218 (5.50%)  10/215 (4.65%)  2/139 (1.44%)  6/137 (4.38%) 
Bursitis  1  6/218 (2.75%)  5/215 (2.33%)  1/139 (0.72%)  0/137 (0.00%) 
Musculoskeletal pain  1  4/218 (1.83%)  7/215 (3.26%)  1/139 (0.72%)  0/137 (0.00%) 
Osteoarthritis  1  6/218 (2.75%)  4/215 (1.86%)  0/139 (0.00%)  2/137 (1.46%) 
Rheumatoid arthritis  1  19/218 (8.72%)  22/215 (10.23%)  6/139 (4.32%)  6/137 (4.38%) 
Rheumatoid nodule  1  1/218 (0.46%)  5/215 (2.33%)  0/139 (0.00%)  0/137 (0.00%) 
Nervous system disorders         
Dizziness  1  3/218 (1.38%)  2/215 (0.93%)  0/139 (0.00%)  3/137 (2.19%) 
Headache  1  18/218 (8.26%)  11/215 (5.12%)  4/139 (2.88%)  9/137 (6.57%) 
Paraesthesia  1  3/218 (1.38%)  5/215 (2.33%)  1/139 (0.72%)  1/137 (0.73%) 
Psychiatric disorders         
Insomnia  1  3/218 (1.38%)  4/215 (1.86%)  0/139 (0.00%)  3/137 (2.19%) 
Respiratory, thoracic and mediastinal disorders         
Cough  1  4/218 (1.83%)  5/215 (2.33%)  3/139 (2.16%)  4/137 (2.92%) 
Oropharyngeal pain  1  10/218 (4.59%)  5/215 (2.33%)  0/139 (0.00%)  1/137 (0.73%) 
Skin and subcutaneous tissue disorders         
Alopecia  1  3/218 (1.38%)  5/215 (2.33%)  0/139 (0.00%)  0/137 (0.00%) 
Dermatitis allergic  1  1/218 (0.46%)  0/215 (0.00%)  1/139 (0.72%)  3/137 (2.19%) 
Rash  1  7/218 (3.21%)  4/215 (1.86%)  1/139 (0.72%)  3/137 (2.19%) 
Vascular disorders         
Hypertension  1  20/218 (9.17%)  10/215 (4.65%)  4/139 (2.88%)  5/137 (3.65%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis
Phone: 862-778-8300
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01350804     History of Changes
Obsolete Identifiers: NCT01640938
Other Study ID Numbers: CAIN457F2309
2011-000102-21 ( EudraCT Number )
First Submitted: May 9, 2011
First Posted: May 10, 2011
Results First Submitted: January 26, 2016
Results First Posted: May 23, 2016
Last Update Posted: May 23, 2016