A Study in Participants With Moderate to Severe Rheumatoid Arthritis (RA-BEGIN)

• ClinicalTrials.gov Identifier: NCT01711359
• Recruitment Status: Completed
• First Posted: October 22, 2012
• Results First Posted: August 15, 2017
• Last Update Posted: September 19, 2019
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

• 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: Drug: Baricitinib; Drug: Methotrexate; Drug: Baricitinib Placebo; Drug: MTX Placebo; Drug: Folic Acid
• Enrollment: 588

Participant Flow

Recruitment Details
Pre-assignment Details	Participants who did not respond (nonresponders) to study drug were eligible for rescue treatment beginning at Week 24. Nonresponders were defined as lack of improvement of at least 20% in both tender joint count and swollen joint count.

Arm/Group Title	Methotrexate	Baricitinib	Baricitinib + MTX
Arm/Group Description	Methotrexate (MTX) administered orally once weekly with dose ranging from 10 to 20 milligram (mg) per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Period Title: Treatment Period
Started	213	160	215
Received at Least One Dose of Study Drug	210	159	215
Rescued	26	7	6
Completed	161	136	173
Not Completed	52	24	42
Reason Not Completed
Withdrawal by Subject	18	7	13
Lack of Efficacy	13	2	2
Adverse Event	8	10	24
Physician Decision	4	3	2
Death	3	0	0
Entry Criteria Not Met	1	0	0
Sponsor Decision	1	0	0
Lost to Follow-up	1	1	1
Randomized, Not Treated	3	1	0
Period Title: Follow Up
Started	25 [1]	15 [1]	28 [2]
Completed	0	0	0
Not Completed	25	15	28
[1] Participants from treatment who entered the post-treatment follow-up period.; [2] Participants from treatment and rescue who entered the post-treatment follow-up period.

Baseline Characteristics

Arm/Group Title		Methotrexate	Baricitinib	Baricitinib + MTX	Total
Arm/Group Description		Methotrexate (MTX) administered orally once weekly with dose ranging from 10 to 20 milligram (mg) per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Total of all reporting groups
Overall Number of Baseline Participants		210	159	215	584
Baseline Analysis Population Description		Modified Intent-to-Treat (mITT) population includes all randomized participants who received at least 1 dose of the study drug.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	210 participants	159 participants	215 participants	584 participants
		50.5 (13.4)	50.9 (13.0)	48.5 (13.5)	49.9 (13.4)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	210 participants	159 participants	215 participants	584 participants
	Female	148 70.5%	121 76.1%	156 72.6%	425 72.8%
	Male	62 29.5%	38 23.9%	59 27.4%	159 27.2%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	210 participants	159 participants	215 participants	584 participants
	American Indian or Alaska Native	11 5.2%	10 6.3%	20 9.3%	41 7.0%
	Asian	60 28.6%	44 27.7%	61 28.4%	165 28.3%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	10 4.8%	5 3.1%	10 4.7%	25 4.3%
	White	128 61.0%	98 61.6%	123 57.2%	349 59.8%
	More than one race	1 0.5%	2 1.3%	1 0.5%	4 0.7%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	210 participants	159 participants	215 participants	584 participants
Argentina		41 19.5%	29 18.2%	33 15.3%	103 17.6%
Austria		1 0.5%	1 0.6%	1 0.5%	3 0.5%
Belgium		6 2.9%	10 6.3%	11 5.1%	27 4.6%
Brazil		8 3.8%	3 1.9%	9 4.2%	20 3.4%
Canada		5 2.4%	5 3.1%	7 3.3%	17 2.9%
Germany		5 2.4%	5 3.1%	4 1.9%	14 2.4%
Greece		0 0.0%	0 0.0%	1 0.5%	1 0.2%
India		18 8.6%	12 7.5%	17 7.9%	47 8.0%
Italy		8 3.8%	2 1.3%	4 1.9%	14 2.4%
Japan		36 17.1%	29 18.2%	39 18.1%	104 17.8%
Mexico		12 5.7%	14 8.8%	20 9.3%	46 7.9%
Portugal		1 0.5%	0 0.0%	2 0.9%	3 0.5%
Russian Federation		11 5.2%	13 8.2%	12 5.6%	36 6.2%
South Africa		7 3.3%	4 2.5%	9 4.2%	20 3.4%
Korea, Republic of		4 1.9%	1 0.6%	2 0.9%	7 1.2%
Sweden		3 1.4%	0 0.0%	1 0.5%	4 0.7%
United Kingdom		7 3.3%	3 1.9%	4 1.9%	14 2.4%
United States		37 17.6%	28 17.6%	39 18.1%	104 17.8%
Duration of Rheumatoid Arthritis; Median (Inter-Quartile Range); Unit of measure: Years
	Number Analyzed	210 participants	159 participants	215 participants	584 participants
		0.2; (0.1 to 0.6)	0.2; (0.1 to 1.1)	0.2; (0.1 to 1.0)	0.2; (0.1 to 0.8)
Tender Joint Count of 68 evaluable joints; Mean (Standard Deviation); Unit of measure: Number of joints
	Number Analyzed	210 participants	159 participants	215 participants	584 participants
		26.5 (14.8)	26.4 (14.1)	27.7 (14.5)	26.9 (14.5)
Swollen Joint Count of 66 evaluable joints; Mean (Standard Deviation); Unit of measure: Number of joints
	Number Analyzed	210 participants	159 participants	215 participants	584 participants
		16.4 (10.6)	16.1 (9.2)	16.3 (9.5)	16.3 (9.8)
High sensitivity C-reactive protein; Mean (Standard Deviation); Unit of measure: Milligrams per liter (mg/L)
	Number Analyzed	210 participants	159 participants	215 participants	584 participants
		22.34 (21.78)	23.75 (26.24)	24.27 (29.42)	23.44 (25.98)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving American College of Rheumatology 20% Improvement (ACR20)
Description	ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). "ACR20 Responder" is a participant who has at least 20% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity using visual analog scale (VAS), Health Assessment Questionnaire-Disability Index (HAQ-DI), pain due to arthritis, and high-sensitivity C-reactive protein (hsCRP). Participants with missing responses and participants who discontinued study or drug or were rescued before analysis time point were deemed non-responders.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat (mITT) population: all randomized participants who received at least 1 dose of study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using nonresponder imputation (NRI).

Arm/Group Title	Methotrexate	Baricitinib	Baricitinib + MTX
Arm/Group Description:	MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Overall Number of Participants Analyzed	210	159	215
Measure Type: Number; Unit of Measure: Percent of participants
	61.9	76.7	78.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Methotrexate, Baricitinib
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Noninferiority is concluded if the lower bound of the 95% CI for the difference in response rate is >-12%
Method of Estimation	Estimation Parameter	Newcombe-Wilson method
	Estimated Value	14.8
	Confidence Interval	(2-Sided) 95%; 5.5 to 24.1
	Estimation Comments	Estimation Parameter: Newcombe-Wilson method without continuity correction for difference in the response rate (Baricitinib minus Methotrexate).

2. Secondary Outcome

Title	Percentage of Participants Achieving American College of Rheumatology 20% Improvement (ACR20)
Description	ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). "ACR20 Responder" is a participant who has at least 20% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity using visual analog scale (VAS), Health Assessment Questionnaire-Disability Index (HAQ-DI), pain due to arthritis, and high-sensitivity C-reactive protein (hsCRP). Participants with missing responses and participants who discontinued study or drug or were rescued before analysis time point were deemed non-responders.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat (mITT) population: all randomized participants who received at least 1 dose of study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using nonresponder imputation (NRI).

Arm/Group Title	Methotrexate	Baricitinib	Baricitinib + MTX
Arm/Group Description:	MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Overall Number of Participants Analyzed	210	159	215
Measure Type: Number; Unit of Measure: Percent of participants
	55.7	73.0	72.6

3. Secondary Outcome

Title	Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
Description	HAQ-DI 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 are averaged to calculate the HAQ-DI score, which ranges from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicates an improvement in the participant's condition.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

mITT population: all randomized participants who received at least 1 dose of study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using modified baseline observation carried forward (mBOCF).

Arm/Group Title	Methotrexate	Baricitinib	Baricitinib + MTX
Arm/Group Description:	MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Overall Number of Participants Analyzed	210	159	215
Mean (Standard Deviation); Unit of Measure: units on a scale
	-0.73 (0.71)	-1.01 (0.74)	-0.92 (0.74)

4. Secondary Outcome

Title	Change From Baseline in the Disease Activity Score Based on a 28-Joint Count and High-sensitivity C-reactive Protein (DAS28-hsCRP)
Description	Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP) (milligrams per liter), and Patient's Global Assessment of Disease Activity. DAS28 was calculated using the following formula: DAS28-CRP=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.36*natural log(CRP+1)+0.014*Patient's Global VAS+0.96. Scores ranged 1.0-9.4, where lower scores indicated less disease activity.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

mITT population: all randomized participants who received at least 1 dose of study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mBOCF.

Arm/Group Title	Methotrexate	Baricitinib	Baricitinib + MTX
Arm/Group Description:	MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Overall Number of Participants Analyzed	210	159	215
Mean (Standard Deviation); Unit of Measure: units on a scale
	-2.01 (1.51)	-2.74 (1.39)	-2.82 (1.58)

5. Secondary Outcome

Title	Change From Baseline in the Modified Total Sharp Score (mTSS)
Description	X-rays of the hands/wrists and feet were scored for structural progression as measured using the mTSS (van der Heijde 2000). This methodology quantified the extent of bone erosions and joint space narrowing for 44 and 42 joints, with higher scores representing greater damage. The mTSS at a time point is the sum of the erosion (range from 0 to 280) and JSN (range from 0 to 168) scores, for a maximum score of 448.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

mITT population: all randomized participants who received at least 1 dose of study drug and had baseline and at least 1 post-baseline assessments. Missing values due to discontinuation of study, rescue, or missing data were imputed using linear extrapolation (LE).

Arm/Group Title	Methotrexate	Baricitinib	Baricitinib + MTX
Arm/Group Description:	MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Overall Number of Participants Analyzed	191	152	198
Mean (Standard Deviation); Unit of Measure: units on a scale
	0.64 (1.81)	0.43 (1.18)	0.32 (1.14)

6. Secondary Outcome

Title	Percentage of Participants Who Achieved a Simplified Disease Activity Index (SDAI) Score ≤3.3
Description	SDAI is a tool for measurement of disease activity in RA that integrates TJC28, SJC28, acute phase response using C-reactive protein (milligrams per liter), Patient's Global Assessment of Disease Activity using VAS centimeters (cm), and Physician's Global Assessment of Disease Activity using VAS (cm). The SDAI is calculated by summing the values of the 5 components. Lower scores indicated less disease activity. An index-based definition of remission occurs with an SDAI score ≤3.3.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

mITT population: all randomized participants who received at least 1 dose of study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.

Arm/Group Title	Methotrexate	Baricitinib	Baricitinib + MTX
Arm/Group Description:	MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Overall Number of Participants Analyzed	210	159	215
Measure Type: Number; Unit of Measure: percentage of participants
	10.5	22.0	22.8

7. Secondary Outcome

Title	Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response
Description	ACR50 Responder Index is composite of clinical, laboratory, and functional measures in RA. "ACR50 Responder" is a participant who has at least 50% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, HAQ-DI, pain due to arthritis, and hsCRP. Participants with missing responses and participants who discontinued study or drug or were rescued before analysis time point were deemed non-responders.
Time Frame	Week 12, Week 24, Week 52

Outcome Measure Data

Analysis Population Description

mITT population: all randomized participants who received at least 1 dose of study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.

Arm/Group Title	Methotrexate	Baricitinib	Baricitinib + MTX
Arm/Group Description:	MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Overall Number of Participants Analyzed	210	159	215
Measure Type: Number; Unit of Measure: Percent of participants
Week 12	32.9	54.7	60.0
Week 24	43.3	59.7	63.3
Week 52	37.6	57.2	61.9

8. Secondary Outcome

Title	Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
Description	ACR70 Responder Index is composite of clinical, laboratory, and functional measures in RA. "ACR70 Responder" is a participant who has at least 70% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, HAQ-DI, pain due to arthritis, and hsCRP. Participants with missing responses and participants who discontinued study or drug or were rescued before analysis timepoint were deemed non-responders.
Time Frame	Week 12, Week 24, Week 52

Outcome Measure Data

Analysis Population Description

mITT population: all randomized participants who received at least 1 dose of study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.

Arm/Group Title	Methotrexate	Baricitinib	Baricitinib + MTX
Arm/Group Description:	MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Overall Number of Participants Analyzed	210	159	215
Measure Type: Number; Unit of Measure: Percent of participants
Week 12	15.7	30.8	33.5
Week 24	21.4	42.1	39.5
Week 52	25.2	42.1	46.0

9. Secondary Outcome

Title	Change From Baseline in Clinical Disease Activity Index (CDAI) Score
Description	The CDAI is a tool for measurement of disease activity in RA that does not require a laboratory component and was scored by the investigative site. It integrates TJC28 (scored 0-28 with higher scores indicating higher disease activity), SJC28 (scored 0-28 with higher scores indicating higher disease activity), Patient's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity), and Physician's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity). The CDAI is calculated by summing the values of the 4 components. CDAI scores range from 0 to 76; lower scores indicated lower disease activity. A negative change from baseline indicates improvement in condition.
Time Frame	Baseline, Week 24; Baseline, Week 52

Outcome Measure Data

Analysis Population Description

mITT population: all randomized participants who received at least 1 dose of study drug with a baseline value and at least 1 post-baseline value. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using modified last observation carried forward (mLOCF).

Arm/Group Title	Methotrexate	Baricitinib	Baricitinib + MTX
Arm/Group Description:	MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Overall Number of Participants Analyzed	200	157	208
Mean (Standard Deviation); Unit of Measure: units on a scale
Week 24	-22.12 (16.12)	-28.20 (13.96)	-29.86 (14.05)
Week 52	-21.95 (18.07)	-28.94 (14.58)	-30.72 (14.87)

10. Secondary Outcome

Title	Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR)
Description	DAS28 consisted of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), erythrocyte sedimentation rate (ESR) (millimeters per hour), and Patient's Global Assessment of Disease Activity. DAS28 was calculated using the following formula: DAS28-ESR=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.70*natural log(ESR)+0.014*Patient's Global VAS. Scores ranged 1.0-9.4, where lower scores indicated less disease activity.
Time Frame	Baseline, Week 24; Baseline, Week 52

Outcome Measure Data

Analysis Population Description

mITT population: all randomized participants who received at least 1 dose of study drug, with a baseline value and at least 1 post-baseline value. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.

Arm/Group Title	Methotrexate	Baricitinib	Baricitinib + MTX
Arm/Group Description:	MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Overall Number of Participants Analyzed	203	159	209
Mean (Standard Deviation); Unit of Measure: units on a scale
Week 24	-2.20 (1.53)	-2.76 (1.45)	-3.06 (1.46)
Week 52	-2.32 (1.77)	-2.84 (1.57)	-3.22 (1.48)

11. Secondary Outcome

Title	Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Remission
Description	The ACR/EULAR definitions of RA remission include a "Boolean-based definition". The Boolean-based definition of remission occurs when all 4 of the following criteria are met at the same visit: TJC28 ≤1, SJC28 ≤1, acute phase response using C-reactive protein (milligrams per deciliter) ≤1, Patient's Global Assessment of Disease Activity using VAS (cm) ≤1.
Time Frame	Week 12, Week 24, Week 52

Outcome Measure Data

Analysis Population Description

mITT population: all randomized participants who received at least 1 dose of study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.

Arm/Group Title	Methotrexate	Baricitinib	Baricitinib + MTX
Arm/Group Description:	MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Overall Number of Participants Analyzed	210	159	215
Measure Type: Number; Unit of Measure: percentage of participants
Week 12	5.7	13.8	14.4
Week 24	8.6	18.9	16.3
Week 52	11.4	17.0	20.9

12. Secondary Outcome

Title	Change From Baseline in Joint Space Narrowing and Bone Erosion Scores
Description	X-rays of the hands/wrists and feet were assessed for joint space narrowing (JSN) and bone erosions. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, is scored from 0 to 4, with 0 indicating no (normal) JSN and 4 indicating complete loss of joint space, bony ankylosis or luxation. JSN scores ranged from 0-168. A score of 0 would indicate no change and higher scores represent a worsening of joint space narrowing. The bone erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints of the feet. Each joint is scored according to the surface area involved from 0 to 5 for hand joints and 0 to 10 for the foot joints, with 0 indicating no erosion and the highest score (5 for the hand and 10 for the foot) indicating extensive loss of bone from more than one half of the articulating bone. Erosion scores ranged from 0 (no erosion) to 280 (high erosion).
Time Frame	Baseline, Week 24; Baseline, Week 52

Outcome Measure Data

Analysis Population Description

mITT population: all randomized participants who received at least 1 dose of study drug and had baseline and at least 1 post-baseline assessment. Missing values due to discontinuation of study, rescue, or missing data were imputed using LE.

Arm/Group Title		Methotrexate	Baricitinib	Baricitinib + MTX
Arm/Group Description:		MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Overall Number of Participants Analyzed		210	159	215
Mean (Standard Deviation); Unit of Measure: units on a scale
JSN Week 24	Number Analyzed	191 participants	152 participants	198 participants
		0.15 (0.94)	0.08 (0.44)	0.05 (0.44)
JSN Week 52	Number Analyzed	192 participants	154 participants	199 participants
		0.23 (1.00)	0.26 (1.14)	0.08 (0.88)
Bone Erosion Week 24	Number Analyzed	191 participants	152 participants	198 participants
		0.49 (1.14)	0.35 (0.92)	0.27 (0.95)
Bone Erosion Week 52	Number Analyzed	192 participants	154 participants	199 participants
		0.80 (1.80)	0.55 (1.48)	0.33 (1.21)

13. Secondary Outcome

Title	Change From Baseline in Duration of Morning Joint Stiffness
Description	Participants reported the duration of their morning joint stiffness (MJS) in hours and minutes. The participants were asked about their duration of morning joint stiffness on the day prior to the study visit to capture actual symptoms, since the participant may have had an atypical morning routine on the day of the study visit. If morning joint stiffness duration was longer than 12 hours (720 minutes), it was truncated to 720 minutes for statistical presentations and analyses. A decrease in duration of morning joint stiffness indicated an improvement in the participant's condition.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

mITT population: all randomized participants who received at least 1 dose of study drug, with a baseline value and at least 1 post-baseline value. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.

Arm/Group Title	Methotrexate	Baricitinib	Baricitinib + MTX
Arm/Group Description:	MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Overall Number of Participants Analyzed	204	159	209
Median (95% Confidence Interval); Unit of Measure: Minutes
	-40.0; (-55.0 to -30.0)	-55.0; (-60.0 to -40.0)	-60.0; (-80.0 to -50.0)

14. Secondary Outcome

Title	Change From Baseline in Worst Tiredness Numeric Rating Scale (NRS)
Description	Participants rated their tiredness by selecting a number from 0 to 10 that best described their worst tiredness during the last 24 hours, where 0 represents "no tiredness" and 10 represents "as bad as you can imagine".
Time Frame	Baseline, Week 24; Baseline Week 52

Outcome Measure Data

Analysis Population Description

mITT population: all randomized participants who received at least 1 dose of study drug, with a baseline value and at least 1 post-baseline value. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.

Arm/Group Title	Methotrexate	Baricitinib	Baricitinib + MTX
Arm/Group Description:	MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Overall Number of Participants Analyzed	204	159	209
Mean (Standard Deviation); Unit of Measure: units on a scale
Week 24	-2.2 (2.7)	-3.0 (3.1)	-3.0 (2.8)
Week 52	-2.3 (2.8)	-2.9 (3.1)	-3.0 (2.9)

15. Secondary Outcome

Title	Change From Baseline in Worst Joint Pain Numeric Rating Scale (NRS)
Description	Participants rated their joint pain by selecting a number from 0 to 10 that best described their worst joint pain during the last 24 hours, where 0 represents "no pain" and 10 represents "pain as bad as you can imagine".
Time Frame	Baseline, Week 24; Baseline Week 52

Outcome Measure Data

Analysis Population Description

mITT population: all randomized participants who received at least 1 dose of study drug, with a baseline value and at least 1 post-baseline value. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.

Arm/Group Title	Methotrexate	Baricitinib	Baricitinib + MTX
Arm/Group Description:	MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Overall Number of Participants Analyzed	204	159	209
Mean (Standard Deviation); Unit of Measure: units on a scale
Week 24	-2.8 (2.5)	-3.9 (2.7)	-3.9 (2.6)
Week 52	-3.0 (2.8)	-3.9 (2.9)	-4.1 (2.7)

16. Secondary Outcome

Title	Change From Baseline in Mental Component Score (MCS) and Physical Component Score (PCS) of the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute (SF-36v2 Acute)
Description	The 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, and 2 component scores (MCS and PCS). MCS consisted of social functioning, vitality, mental health, and role-emotional scales. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale with higher scores indicating better health status or functioning.
Time Frame	Baseline, Week 24; Baseline Week 52

Outcome Measure Data

Analysis Population Description

mITT population: all randomized participants who received at least 1 dose of study drug, with a baseline value and at least 1 post-baseline value. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.

Arm/Group Title	Methotrexate	Baricitinib	Baricitinib + MTX
Arm/Group Description:	MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Overall Number of Participants Analyzed	202	159	207
Mean (Standard Deviation); Unit of Measure: units on a scale
MCS Week 24	3.4 (10.8)	5.9 (11.7)	4.6 (11.6)
MCS Week 52	2.4 (10.9)	5.8 (11.9)	5.0 (11.5)
PCS Week 24	9.4 (9.2)	12.5 (9.1)	13.2 (9.6)
PCS Week 52	9.4 (10.1)	11.6 (9.6)	13.3 (9.8)

17. Secondary Outcome

Title	Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores
Description	European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a standardized measure of health status of the participant. One component consists of a descriptive system of the respondent's health comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using the United Kingdom (UK) algorithm, with scores ranging from -0.594 to 1, and the United States (US) algorithm, with scores ranging from -0.109 to 1. A higher score indicates better health state.
Time Frame	Baseline, Week 24; Baseline Week 52

Outcome Measure Data

Analysis Population Description

mITT population: all randomized participants who received at least 1 dose of study drug, with a baseline value and at least 1 post-baseline value. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.

Arm/Group Title	Methotrexate	Baricitinib	Baricitinib + MTX
Arm/Group Description:	MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Overall Number of Participants Analyzed	202	159	207
Mean (Standard Deviation); Unit of Measure: units on a scale
Index Score (US Algorithm) Week 24	0.142 (0.189)	0.197 (0.164)	0.194 (0.180)
Index Score (US Algorithm) Week 52	0.138 (0.203)	0.186 (0.177)	0.185 (0.186)
Index Score (UK Algorithm) Week 24	0.205 (0.274)	0.285 (0.241)	0.282 (0.255)
Index Score (UK Algorithm) Week 52	0.197 (0.294)	0.271 (0.258)	0.268 (0.266)

18. Secondary Outcome

Title	Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health)
Description	A second component of the EQ-5D-5L is a self-perceived health score which is assessed using a VAS that ranges from 0 to 100 millimeter (mm), where 0 indicates the worst health you can imagine and 100 indicates the best health you can imagine.
Time Frame	Baseline, Week 24; Baseline Week 52

Outcome Measure Data

Analysis Population Description

mITT population: all randomized participants who received at least 1 dose of study drug, with a baseline value and at least 1 post-baseline value. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.

Arm/Group Title	Methotrexate	Baricitinib	Baricitinib + MTX
Arm/Group Description:	MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Overall Number of Participants Analyzed	202	159	207
Mean (Standard Deviation); Unit of Measure: millimeter
Self-Perceived Health Week 24	14.5 (28.3)	24.1 (26.0)	21.4 (31.4)
Self-Perceived Health Week 52	13.6 (30.1)	24.5 (28.7)	24.5 (30.6)

19. Secondary Outcome

Title	Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scores
Description	The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale is a13-item, symptom-specific questionnaire that specifically assesses the participant's self-reported severity of fatigue and its impact upon daily activities and functioning. The FACIT-F uses a numeric rating scale of 0 ("Not at all") to 4 ("Very much") for each item to assess fatigue and its impact in the past 7 days. Total scores range from 0 to 52, with higher scores indicating less fatigue.
Time Frame	Baseline, Week 24; Baseline Week 52

Outcome Measure Data

Analysis Population Description

mITT population: all randomized participants who received at least 1 dose of study drug, with a baseline value and at least 1 post-baseline value. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.

Arm/Group Title	Methotrexate	Baricitinib	Baricitinib + MTX
Arm/Group Description:	MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Overall Number of Participants Analyzed	204	159	209
Mean (Standard Deviation); Unit of Measure: units on a scale
Week 24	9.3 (11.2)	13.0 (10.8)	12.3 (11.5)
Week 52	9.1 (10.9)	11.3 (10.8)	12.6 (11.8)

20. Secondary Outcome

Title	Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores
Description	The Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) questionnaire was developed to measure the effect of general health and symptom severity on work productivity and regular activities in the 7 days prior to the visit. It contains 6 items covering overall work productivity (health), overall work productivity (symptom), impairment of regular activities (health), and impairment of regular activities (symptom). Scores are calculated as impairment percentages. The WPAI-RA yields four types of scores: Absenteeism (work time missed), Presenteeism (impairment at work), Work productivity loss (overall work impairment), and Activity impairment.
Time Frame	Baseline, Week 24; Baseline Week 52

Outcome Measure Data

Analysis Population Description

mITT population: all randomized participants who received at least 1 dose of study drug, with a baseline value and an observed value at the time point being summarized.

Arm/Group Title	Methotrexate	Baricitinib	Baricitinib + MTX
Arm/Group Description:	MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Overall Number of Participants Analyzed	210	159	215
Mean (Standard Deviation); Unit of Measure: Percentage of Impairment
Absenteeism Week 24 (n=76, 56, 90)	-3.6 (35.5)	-8.7 (30.4)	-7.6 (26.5)
Absenteeism Week 52 (n=52, 51, 71)	-3.0 (29.2)	-8.4 (29.7)	-7.3 (21.8)
Presenteeism Week 24(n=70, 51, 86)	-19 (25)	-26 (27)	-32 (26)
Presenteeism Week 52 (n=51, 47, 75)	-26 (26)	-27 (24)	-33 (25)
Work Productivity Loss Week 24 (n=70, 71, 86)	-17.8 (30.2)	-25.6 (29.1)	-30.9 (29.6)
Work Productivity Loss Week 52 (n=51, 47, 75)	-24.1 (30.5)	-27.6 (27.3)	-33.8 (27.5)
Activity Impairment Week 24 (n=184, 145, 192)	-25 (26)	-36 (28)	-31 (28)
Activity Impairment Week 52 (n=141, 131, 172)	-28 (27)	-34 (27)	-37 (27)

21. Secondary Outcome

Title	Population Pharmacokinetics (PK): Peak Concentration at Steady State (Cmax,ss) of Baricitinib
Description	[Not Specified]
Time Frame	Week 0: 15 and 60 minutes postdose; Week 4: 2 to 4 hours post-dose; Week 8: 4 to 6 hours post-dose; Week 12; Week 24; Week 32; Pre-dose

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug (during study or rescue treatment) with evaluable PK data.

Arm/Group Title	Baricitinib
Arm/Group Description:	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Overall Number of Participants Analyzed	355
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nanomole/Liter (nmol/L)
	135; (23.1%)

22. Secondary Outcome

Title	Population PK: Area Under the Concentration Versus Time Curve at a Dosing Interval at Steady State (AUCtau,ss) of Baricitinib
Description	[Not Specified]
Time Frame	Week 0: 15 and 60 minutes postdose; Week 4: 2 to 4 hours post-dose; Week 8: 4 to 6 hours post-dose; Week 12; Week 24; Week 32; Pre-dose

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug (during study or rescue treatment) with evaluable PK data.

Arm/Group Title	Baricitinib
Arm/Group Description:	Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
Overall Number of Participants Analyzed	355
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nanomole/Liter (nmol/L)
	1280; (47.2%)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	All enrolled participants including those receiving rescue therapy, with events occurring after rescue accounted separately. Rescue therapy occurred at Week 24 or later, if determined to be nonresponders (lack of improvement of at least 20% in both tender joint count and swollen joint count).
Arm/Group Title	Methotrexate		Baricitinib		Baricitinib + MTX		Rescue Period		Methotrexate - Follow-up		Baricitinib - Follow-up		Baricitinib + MTX - Follow-up
Arm/Group Description	Methotrexate (MTX) administered orally once weekly with dose ranging from 10 to 20 milligram (mg) per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.		Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.		Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.		Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX orally once weekly with dose ranging from 10 to 20 mg per week through Week 52.		No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug.		No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug.		No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug. Includes participants who were rescued to Baricitinib + MTX.
All-Cause Mortality
	Methotrexate		Baricitinib		Baricitinib + MTX		Rescue Period		Methotrexate - Follow-up		Baricitinib - Follow-up		Baricitinib + MTX - Follow-up
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--		--/--		--/--		--/--		--/--
Serious Adverse Events
	Methotrexate		Baricitinib		Baricitinib + MTX		Rescue Period		Methotrexate - Follow-up		Baricitinib - Follow-up		Baricitinib + MTX - Follow-up
	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	20/210 (9.52%)		12/159 (7.55%)		17/215 (7.91%)		1/39 (2.56%)		0/25 (0.00%)		0/15 (0.00%)		0/28 (0.00%)
Cardiac disorders
Atrial fibrillation † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Coronary artery disease † 1	0/210 (0.00%)	0	1/159 (0.63%)	1	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Myocardial infarction † 1	0/210 (0.00%)	0	1/159 (0.63%)	1	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Myocardial ischaemia † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	1/215 (0.47%)	1	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Eye disorders
Cataract † 1	1/210 (0.48%)	1	0/159 (0.00%)	0	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Gastrointestinal disorders
Chronic gastritis † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	1/215 (0.47%)	1	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Duodenal ulcer † 1	0/210 (0.00%)	0	1/159 (0.63%)	1	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Enterocolitis † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	1/215 (0.47%)	1	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Gastric ulcer haemorrhage † 1	1/210 (0.48%)	1	0/159 (0.00%)	0	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Umbilical hernia † 1	1/210 (0.48%)	1	0/159 (0.00%)	0	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
General disorders
Drowning † 1	1/210 (0.48%)	1	0/159 (0.00%)	0	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Fatigue † 1	0/210 (0.00%)	0	1/159 (0.63%)	1	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Non-cardiac chest pain † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	1/215 (0.47%)	1	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Oedema peripheral † 1	0/210 (0.00%)	0	1/159 (0.63%)	1	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Pyrexia † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	1/215 (0.47%)	1	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Hepatobiliary disorders
Cholecystitis † 1	0/210 (0.00%)	0	1/159 (0.63%)	1	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Infections and infestations
Acute hepatitis B † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	1/215 (0.47%)	1	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Bronchitis haemophilus † 1	0/210 (0.00%)	0	1/159 (0.63%)	1	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Campylobacter gastroenteritis † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	1/215 (0.47%)	1	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Cellulitis † 1	1/210 (0.48%)	1	0/159 (0.00%)	0	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Diverticulitis † 1	0/210 (0.00%)	0	1/159 (0.63%)	1	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Escherichia sepsis † 1	1/210 (0.48%)	1	0/159 (0.00%)	0	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Herpes zoster † 1	2/210 (0.95%)	2	1/159 (0.63%)	1	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Infectious colitis † 1	0/210 (0.00%)	0	1/159 (0.63%)	1	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Lung infection † 1	1/210 (0.48%)	1	0/159 (0.00%)	0	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Meningitis bacterial † 1	1/210 (0.48%)	1	0/159 (0.00%)	0	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Pneumocystis jirovecii pneumonia † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	1/215 (0.47%)	1	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Pneumonia † 1	1/210 (0.48%)	1	1/159 (0.63%)	1	1/215 (0.47%)	1	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Pyelonephritis acute † 1	0/210 (0.00%)		0/159 (0.00%)	0	1/215 (0.47%)	1	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Sepsis † 1	1/210 (0.48%)	1	1/159 (0.63%)	1	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Urinary tract infection † 1	1/210 (0.48%)	1	0/159 (0.00%)	0	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Injury, poisoning and procedural complications
Fall † 1	2/210 (0.95%)	2	0/159 (0.00%)	0	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Femur fracture † 1	1/210 (0.48%)	1	0/159 (0.00%)	0	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Overdose † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	1/215 (0.47%)	1	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Spinal compression fracture † 1	2/210 (0.95%)	2	0/159 (0.00%)	0	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Tibia fracture † 1	1/210 (0.48%)	1	0/159 (0.00%)	0	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Toxicity to various agents † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	1/215 (0.47%)	1	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Wrist fracture † 1	1/210 (0.48%)	1	0/159 (0.00%)	0	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Investigations
Lymphocyte count decreased † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	1/215 (0.47%)	1	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis † 1	1/210 (0.48%)	1	0/159 (0.00%)	0	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma † 1	0/210 (0.00%)	0	1/159 (0.63%)	1	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Gallbladder adenosquamous carcinoma † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	1/215 (0.47%)	1	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Malignant melanoma † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	1/215 (0.47%)	1	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Nervous system disorders
Cerebral haemorrhage † 1	1/210 (0.48%)	1	0/159 (0.00%)	0	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Headache † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	1/215 (0.47%)	1	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Migraine † 1	0/210 (0.00%)	0	1/159 (0.63%)	1	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Syncope † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	1/215 (0.47%)	1	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Renal and urinary disorders
Acute kidney injury † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	1/215 (0.47%)	1	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Reproductive system and breast disorders
Genital prolapse † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	1/215 (0.47%)	1	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Asthma † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	1/215 (0.47%)	1	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Chronic obstructive pulmonary disease † 1	1/210 (0.48%)	1	0/159 (0.00%)	0	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Pneumothorax spontaneous † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	1/215 (0.47%)	1	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Pulmonary embolism † 1	1/210 (0.48%)	1	0/159 (0.00%)	0	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Pulmonary fibrosis † 1	1/210 (0.48%)	1	0/159 (0.00%)	0	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 18.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	2%
	Methotrexate		Baricitinib		Baricitinib + MTX		Rescue Period		Methotrexate - Follow-up		Baricitinib - Follow-up		Baricitinib + MTX - Follow-up
	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	115/210 (54.76%)		81/159 (50.94%)		129/215 (60.00%)		21/39 (53.85%)		2/25 (8.00%)		2/15 (13.33%)		0/28 (0.00%)
Blood and lymphatic system disorders
Anaemia † 1	2/210 (0.95%)	2	2/159 (1.26%)	2	6/215 (2.79%)	6	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Thrombocytosis † 1	0/210 (0.00%)	0	4/159 (2.52%)	4	3/215 (1.40%)	3	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Cardiac disorders
Cardiomegaly † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Left ventricular hypertrophy † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Ear and labyrinth disorders
Ear pruritus † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Endocrine disorders
Hypothyroidism † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Eye disorders
Scleritis † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Scleromalacia † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Gastrointestinal disorders
Constipation † 1	3/210 (1.43%)	3	2/159 (1.26%)	3	7/215 (3.26%)	8	0/39 (0.00%)	0	0/25 (0.00%)	0	1/15 (6.67%)	1	0/28 (0.00%)	0
Abdominal discomfort † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Large intestine polyp † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Stomatitis † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Abdominal pain upper † 1	6/210 (2.86%)	6	3/159 (1.89%)	4	1/215 (0.47%)	1	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Diarrhoea † 1	12/210 (5.71%)	15	3/159 (1.89%)	3	5/215 (2.33%)	6	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Dyspepsia † 1	1/210 (0.48%)	1	3/159 (1.89%)	3	8/215 (3.72%)	9	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Gastrooesophageal reflux disease † 1	1/210 (0.48%)	1	0/159 (0.00%)	0	5/215 (2.33%)	5	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Nausea † 1	13/210 (6.19%)	16	7/159 (4.40%)	7	20/215 (9.30%)	26	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Vomiting † 1	6/210 (2.86%)	6	5/159 (3.14%)	5	5/215 (2.33%)	8	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
General disorders
Oedema peripheral † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	0/39 (0.00%)	0	1/25 (4.00%)	1	0/15 (0.00%)	0	0/28 (0.00%)	0
Fatigue † 1	5/210 (2.38%)	5	3/159 (1.89%)	3	8/215 (3.72%)	8	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Pyrexia † 1	4/210 (1.90%)	5	1/159 (0.63%)	1	5/215 (2.33%)	6	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Hepatobiliary disorders
Hepatic function abnormal † 1	5/210 (2.38%)	5	1/159 (0.63%)	1	8/215 (3.72%)	9	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Infections and infestations
Hepatitis E † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Herpes zoster † 1	0/210 (0.00%)	0	3/159 (1.89%)	3	5/215 (2.33%)	5	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Nasopharyngitis † 1	17/210 (8.10%)	20	16/159 (10.06%)	21	21/215 (9.77%)	32	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Pharyngitis † 1	4/210 (1.90%)	6	2/159 (1.26%)	2	7/215 (3.26%)	9	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Upper respiratory tract infection † 1	15/210 (7.14%)	15	12/159 (7.55%)	14	16/215 (7.44%)	19	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Vaginal infection † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	1/28 (3.57%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Bronchitis † 1	4/210 (1.90%)	4	5/159 (3.14%)	5	9/215 (4.19%)	10	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Gastroenteritis † 1	4/210 (1.90%)	4	10/159 (6.29%)	10	6/215 (2.79%)	6	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Influenza † 1	4/210 (1.90%)	4	7/159 (4.40%)	7	11/215 (5.12%)	11	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Rhinitis † 1	7/210 (3.33%)	7	1/159 (0.63%)	1	2/215 (0.93%)	3	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Sinusitis † 1	5/210 (2.38%)	5	1/159 (0.63%)	1	7/215 (3.26%)	8	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Urinary tract infection † 1	7/210 (3.33%)	7	6/159 (3.77%)	7	14/215 (6.51%)	16	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Vulvovaginal candidiasis † 1	1/148 (0.68%)	1	0/159 (0.00%)	0	6/156 (3.85%)	8	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Injury, poisoning and procedural complications
Ankle fracture † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Arthropod bite † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Joint injury † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Thermal burn † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	2/39 (5.13%)	2	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Wrist fracture † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	5/210 (2.38%)	5	1/159 (0.63%)	1	13/215 (6.05%)	15	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Aspartate aminotransferase increased † 1	3/210 (1.43%)	3	0/159 (0.00%)	0	7/215 (3.26%)	8	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Blood creatine phosphokinase increased † 1	2/210 (0.95%)	2	4/159 (2.52%)	5	10/215 (4.65%)	11	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Blood creatinine increased † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Liver function test abnormal † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Lymphocyte count increased † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Weight increased † 1	3/210 (1.43%)	3	4/159 (2.52%)	4	1/215 (0.47%)	1	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Metabolism and nutrition disorders
Hypercholesterolaemia † 1	3/210 (1.43%)	3	4/159 (2.52%)	4	4/215 (1.86%)	4	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Hyperlipidaemia † 1	1/210 (0.48%)	1	3/159 (1.89%)	3	6/215 (2.79%)	6	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Dyslipidaemia † 1	2/210 (0.95%)	2	2/159 (1.26%)	2	8/215 (3.72%)	8	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	0/39 (0.00%)	0	1/25 (4.00%)	1	0/15 (0.00%)	0	0/28 (0.00%)	0
Back pain † 1	5/210 (2.38%)	5	3/159 (1.89%)	3	9/215 (4.19%)	10	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Muscle spasms † 1	1/210 (0.48%)	2	2/159 (1.26%)	2	7/215 (3.26%)	7	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Rheumatoid arthritis † 1	7/210 (3.33%)	7	3/159 (1.89%)	3	1/215 (0.47%)	1	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Nervous system disorders
Dizziness † 1	5/210 (2.38%)	6	1/159 (0.63%)	1	3/215 (1.40%)	4	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Headache † 1	3/210 (1.43%)	3	5/159 (3.14%)	6	6/215 (2.79%)	7	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Sciatica † 1	0/210 (0.00%)	0	4/159 (2.52%)	4	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Pregnancy, puerperium and perinatal conditions
Pregnancy † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	1/28 (3.57%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Psychiatric disorders
Depression † 1	4/210 (1.90%)	4	6/159 (3.77%)	6	2/215 (0.93%)	2	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Renal and urinary disorders
Polyuria † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Catarrh † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Cough † 1	13/210 (6.19%)	14	5/159 (3.14%)	7	6/215 (2.79%)	6	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Sinus congestion † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Skin and subcutaneous tissue disorders
Eczema asteatotic † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	1/15 (6.67%)	1	0/28 (0.00%)	0
Miliaria † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	1/15 (6.67%)	1	0/28 (0.00%)	0
Seborrhoeic dermatitis † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	0/39 (0.00%)	0	0/25 (0.00%)	0	1/15 (6.67%)	1	0/28 (0.00%)	0
Dermatitis † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Petechiae † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Pruritus † 1	0/210 (0.00%)	0	0/159 (0.00%)	0	0/215 (0.00%)	0	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Alopecia † 1	5/210 (2.38%)	5	1/159 (0.63%)	1	6/215 (2.79%)	6	0/39 (0.00%)	0	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
Vascular disorders
Hypertension † 1	7/210 (3.33%)	7	2/159 (1.26%)	2	13/215 (6.05%)	13	1/39 (2.56%)	1	0/25 (0.00%)	0	0/15 (0.00%)	0	0/28 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 18.0

Limitations and Caveats

[Not Specified]

More Information

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.

Results Point of Contact

• Name/Title: Chief Medical Officer
• Organization: Eli Lilly and Company
• Phone: 800-545-5979

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Taylor PC, Alten R, Alvaro Gracia JM, Kaneko Y, Walls C, Quebe A, Jia B, Bello N, Terres JR, Fleischmann R. Achieving pain control in early rheumatoid arthritis with baricitinib monotherapy or in combination with methotrexate versus methotrexate monotherapy. RMD Open. 2022 Mar;8(1):e001994. doi: 10.1136/rmdopen-2021-001994.

Taylor PC, Takeuchi T, Burmester GR, Durez P, Smolen JS, Deberdt W, Issa M, Terres JR, Bello N, Winthrop KL. Safety of baricitinib for the treatment of rheumatoid arthritis over a median of 4.6 and up to 9.3 years of treatment: final results from long-term extension study and integrated database. Ann Rheum Dis. 2022 Mar;81(3):335-343. doi: 10.1136/annrheumdis-2021-221276. Epub 2021 Oct 27.

van der Heijde D, Kartman CE, Xie L, Beattie S, Schlichting D, Mo D, Durez P, Tanaka Y, Fleischmann R. Radiographic Progression of Structural Joint Damage Over 5 Years of Baricitinib Treatment in Patients With Rheumatoid Arthritis: Results From RA-BEYOND. J Rheumatol. 2022 Feb;49(2):133-141. doi: 10.3899/jrheum.210346. Epub 2021 Sep 15.

Emery P, Tanaka Y, Cardillo T, Schlichting D, Rooney T, Beattie S, Helt C, Smolen JS. Temporary interruption of baricitinib: characterization of interruptions and effect on clinical outcomes in patients with rheumatoid arthritis. Arthritis Res Ther. 2020 May 15;22(1):115. doi: 10.1186/s13075-020-02199-8. Erratum In: Arthritis Res Ther. 2020 Jul 2;22(1):166.

Fleischmann R, Takeuchi T, Schiff M, Schlichting D, Xie L, Issa M, Stoykov I, Lisse J, Martinez-Osuna P, Rooney T, Zerbini CAF. Efficacy and Safety of Long-Term Baricitinib With and Without Methotrexate for the Treatment of Rheumatoid Arthritis: Experience With Baricitinib Monotherapy Continuation or After Switching From Methotrexate Monotherapy or Baricitinib Plus Methotrexate. Arthritis Care Res (Hoboken). 2020 Aug;72(8):1112-1121. doi: 10.1002/acr.24007.

Smolen JS, Genovese MC, Takeuchi T, Hyslop DL, Macias WL, Rooney T, Chen L, Dickson CL, Riddle Camp J, Cardillo TE, Ishii T, Winthrop KL. Safety Profile of Baricitinib in Patients with Active Rheumatoid Arthritis with over 2 Years Median Time in Treatment. J Rheumatol. 2019 Jan;46(1):7-18. doi: 10.3899/jrheum.171361. Epub 2018 Sep 15. Erratum In: J Rheumatol. 2019 Dec;46(12):1648-1649.

Taylor PC, Kremer JM, Emery P, Zuckerman SH, Ruotolo G, Zhong J, Chen L, Witt S, Saifan C, Kurzawa M, Otvos JD, Connelly MA, Macias WL, Schlichting DE, Rooney TP, de Bono S, McInnes IB. Lipid profile and effect of statin treatment in pooled phase II and phase III baricitinib studies. Ann Rheum Dis. 2018 Jul;77(7):988-995. doi: 10.1136/annrheumdis-2017-212461. Epub 2018 Feb 20.

Schiff M, Takeuchi T, Fleischmann R, Gaich CL, DeLozier AM, Schlichting D, Kuo WL, Won JE, Carmack T, Rooney T, Durez P, Shaikh S, Hidalgo RP, van Vollenhoven R, Zerbini CAF. Patient-reported outcomes of baricitinib in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment. Arthritis Res Ther. 2017 Sep 18;19(1):208. doi: 10.1186/s13075-017-1410-1.

Fleischmann R, Schiff M, van der Heijde D, Ramos-Remus C, Spindler A, Stanislav M, Zerbini CA, Gurbuz S, Dickson C, de Bono S, Schlichting D, Beattie S, Kuo WL, Rooney T, Macias W, Takeuchi T. Baricitinib, Methotrexate, or Combination in Patients With Rheumatoid Arthritis and No or Limited Prior Disease-Modifying Antirheumatic Drug Treatment. Arthritis Rheumatol. 2017 Mar;69(3):506-517. doi: 10.1002/art.39953.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01711359
• Other Study ID Numbers: 14062; I4V-MC-JADZ ( Other Identifier: Eli Lilly and Company )
• First Submitted: October 18, 2012
• First Posted: October 22, 2012
• Results First Submitted: March 10, 2017
• Results First Posted: August 15, 2017
• Last Update Posted: September 19, 2019