A Study in Moderate to Severe Rheumatoid Arthritis (RA-BEAM)

• ClinicalTrials.gov Identifier: NCT01710358
• Recruitment Status: Completed
• First Posted: October 19, 2012
• Results First Posted: August 15, 2017
• Last Update Posted: September 18, 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: Adalimumab; Drug: Baricitinib; Drug: Methotrexate; Drug: Adalimumab Placebo; Drug: Baricitinib Placebo
• Enrollment: 1307

Participant Flow

Recruitment Details
Pre-assignment Details	Participants who did not respond (nonresponders) to study drug were eligible for rescue treatment beginning at Week16. Participants not rescued at Week 16 may be rescued at the discretion of the investigator anytime thereafter. Nonresponders were defined as lack of improvement of at least 20% in both tender joint count and swollen joint count.

Arm/Group Title	Placebo	Baricitinib	Adalimumab
Arm/Group Description	Placebo administered orally (PO) once daily (QD) through Week 24 and placebo administered by subcutaneous (SC) injection every 2 weeks through Week 50. At Week 24, participants were given baricitinib 4 milligram (mg) orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily through Week 52. Participants continued to take background methotrexate (MTX) therapy throughout study.	Baricitinib 4 mg administered orally once daily through Week 52 and an adalimumab placebo SC injection every 2 weeks through Week 50. Starting at Week 16, nonresponder participants originally randomized to baricitinib continued to receive baricitinib 4 mg administered orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.	Adalimumab 40 mg administered by SC injection every 2 weeks through Week 50 and baricitinib placebo orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.
Period Title: Treatment Period Part A (Weeks 0 to 24)
Started	489	488	330
Received at Least 1 Dose of Study Drug	488	487	330
Rescued	128	35	40
Completed	438 [1]	459 [1]	307 [1]
Not Completed	51	29	23
Reason Not Completed
Adverse Event	15	18	7
Death	0	2	0
Entry Criteria Not Met	0	1	1
Lack of Efficacy	15	1	3
Lost to Follow-up	0	1	0
Physician Decision	1	0	0
Sponsor Decision	4	0	0
Withdrawal by Subject	15	5	12
Randomized But Not Treated	1	1	0
[1] Includes all participants rescued during Part A.
Period Title: Treatment Period Part B (Weeks 24 to 52)
Started	310 [1]	424 [1]	267 [1]
Received at Least 1 Dose of Study Drug	306 [2]	424	267
Rescued	5	8	11
Completed	294 [3]	402 [3]	252 [3]
Not Completed	16	22	15
Reason Not Completed
Adverse Event	10	16	5
Death	1	0	1
Lack of Efficacy	0	0	1
Lost to Follow-up	0	0	1
Physician Decision	0	1	0
Sponsor Decision	1	2	0
Withdrawal by Subject	4	3	7
[1] Excludes participants rescued during Part A.; [2] Participants originally randomized to placebo received baricitinib during Part B.; [3] Includes all participants rescued during Part B.
Period Title: Rescue Period
Started	0 [1]	227 [2]	0 [1]
Completed	0	196	0
Not Completed	0	31	0
Reason Not Completed
Adverse Event	0	15	0
Death	0	1	0
Lack of Efficacy	0	7	0
Withdrawal by Subject	0	8	0
[1] Participants who were nonresponders based on tender/swollen joint count entered into rescue group.; [2] Baricitinib 4 mg administered PO QD through Week 52. Participants continued background MTX therapy.
Period Title: Follow-up Period
Started	33 [1]	76 [2]	20 [1]
Completed	33	76	20
Not Completed	0	0	0
[1] Participants from treatment who entered the post-treatment follow-up period.; [2] Rescued participants who entered post-treatment follow-up are included in Baricitinib 4mg follow up.

Baseline Characteristics

Arm/Group Title		Placebo	Baricitinib	Adalimumab	Total
Arm/Group Description		Placebo administered orally once daily through Week 24 and placebo administered by subcutaneous (SC) injection every 2 weeks through Week 50. At Week 24, participants were given baricitinib 4 milligram (mg) orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally daily through Week 52. Participants continued to take background methotrexate (MTX) therapy throughout study.	Baricitinib 4 mg administered orally once daily through Week 52 and an adalimumab placebo SC injection every 2 weeks through Week 50. Starting at Week 16, nonresponder participants originally randomized to baricitinib continued to receive baricitinib 4 mg administered orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.	Adalimumab 40 mg administered by SC injection every 2 weeks through Week 50 and baricitinib placebo orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily through Week 52. Participants continued to take background MTX) therapy throughout study.	Total of all reporting groups
Overall Number of Baseline Participants		488	487	330	1305
Baseline Analysis Population Description		Modified Intent-to-Treat (mITT) population: all randomized participants who received at least 1 dose of study drug.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	488 participants	487 participants	330 participants	1305 participants
		53.4 (11.8)	53.5 (12.2)	52.9 (12.3)	53.3 (12.1)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	488 participants	487 participants	330 participants	1305 participants
	Female	382	375	251	1008
	Male	106	112	79	297
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	488 participants	487 participants	330 participants	1305 participants
	American Indian or Alaska Native	26	19	18	63
	Asian	148	143	101	392
	Native Hawaiian or Other Pacific Islander	0	0	0	0
	Black or African American	4	2	4	10
	White	302	312	204	818
	More than one race	7	11	3	21
	Unknown or Not Reported	1	0	0	1
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	488 participants	487 participants	330 participants	1305 participants
Argentina		91	107	57	255
Belgium		2	3	3	8
Canada		5	4	2	11
China		21	22	11	54
Croatia		1	0	0	1
Czechia		16	10	10	36
France		8	8	7	23
Germany		0	0	2	2
Greece		1	0	2	3
Hungary		18	11	8	37
Japan		93	93	63	249
South Korea		21	21	15	57
Latvia		2	2	5	9
Lithuania		4	12	10	26
Mexico		50	36	39	125
Poland		26	35	19	80
Portugal		1	1	1	3
Romania		8	6	2	16
Russia		27	28	23	78
Slovakia		8	8	4	20
Slovenia		4	1	0	5
South Africa		24	21	11	56
Spain		15	11	5	31
Taiwan		6	5	7	18
United Kingdom		2	6	0	8
United States		34	36	24	94
Duration of Rheumatoid Arthritis; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	488 participants	487 participants	330 participants	1305 participants
		10.4 (8.7)	10.3 (8.8)	9.6 (8.5)	10.1 (8.7)
Tender Joint Count of 68 Evaluable Joints; Mean (Standard Deviation); Unit of measure: Number of Joints
	Number Analyzed	488 participants	487 participants	330 participants	1305 participants
		23.3 (13.5)	23.4 (13.0)	23.4 (13.7)	23.4 (13.3)
Swollen Joint Count of 66 Evaluable Joints; Mean (Standard Deviation); Unit of measure: Number of Joints
	Number Analyzed	488 participants	487 participants	330 participants	1305 participants
		15.5 (9.4)	15.0 (8.2)	15.4 (9.1)	15.3 (8.9)
High Sensitivity C-Reactive Protein (hsCRP); Mean (Standard Deviation); Unit of measure: Milligrams per liter (mg/L)
	Number Analyzed	488 participants	487 participants	330 participants	1305 participants
		19.66 (20.97)	22.20 (22.85)	21.78 (20.83)	21.14 (21.67)

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 timepoint were deemed non-responders.
Time Frame	Week 12

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	Placebo	Baricitinib	Adalimumab
Arm/Group Description:	Placebo administered orally once daily through Week 24 and placebo administered by SC injection every 2 weeks through Week 50. At Week 24, participants were switched to baricitinib 4 mg orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally daily through Week 52. Participants continued to take background MTX therapy throughout study.	Baricitinib 4 mg administered orally once daily through Week 52 and an adalimumab placebo SC injection every 2 weeks through Week 50. Starting at Week 16, nonresponder participants originally randomized to baricitinib continued to receive baricitinib 4 mg administered orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.	Adalimumab 40 mg administered by SC injection every 2 weeks through Week 50 and baricitinib placebo orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.
Overall Number of Participants Analyzed	488	487	330
Measure Type: Number; Unit of Measure: percentage of participants
	40.2	69.6	61.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Baricitinib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

2. 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. 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	Placebo	Baricitinib	Adalimumab
Arm/Group Description:	Placebo administered orally once daily through Week 24 and placebo administered by SC injection every 2 weeks through Week 50. At Week 24, participants were switched to baricitinib 4 mg orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally daily through Week 52. Participants continued to take background MTX therapy throughout study.	Baricitinib 4 mg administered orally once daily through Week 52 and an adalimumab placebo SC injection every 2 weeks through Week 50. Starting at Week 16, nonresponder participants originally randomized to baricitinib continued to receive baricitinib 4 mg administered orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.	Adalimumab 40 mg administered by SC injection every 2 weeks through Week 50 and baricitinib placebo orally once daily through Week 52. Starting at Week 16, participants who are were nonresponders were rescued with baricitinib 4 mg orally once daily through Week 52. Participants will continued to take background MTX therapy throughout study.
Overall Number of Participants Analyzed	452	470	312
Mean (Standard Deviation); Unit of Measure: units on a scale
	0.84 (2.32)	0.35 (1.59)	0.29 (1.47)

3. Secondary Outcome

Title	Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
Description	The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty (0 [without any difficulty], 1 [with some difficulty], 2 [with much difficulty], and 3 [unable to do]) when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate the HAQ-DI score, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

mITT population includes all randomized participants who received at least 1 dose of the 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	Placebo	Baricitinib	Adalimumab
Arm/Group Description:	Placebo administered orally once daily through Week 24 and placebo administered by SC injection every 2 weeks through Week 50. At Week 24, participants were switched to baricitinib 4 mg orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally daily through Week 52. Participants continued to take background MTX therapy throughout study.	Baricitinib 4 mg administered orally once daily through Week 52 and an adalimumab placebo SC injection every 2 weeks through Week 50. Starting at Week 16, nonresponder participants originally randomized to baricitinib will continue to receive baricitinib 4 mg administered orally once daily through Week 52. Participants will continue to take background MTX therapy throughout study.	Adalimumab 40 mg administered by SC injection every 2 weeks through Week 50 and baricitinib placebo orally once daily through Week 52. Starting at Week 16, participants who are nonresponders will be rescued with baricitinib 4 mg orally once daily through Week 52. Participants will continue to take background MTX therapy throughout study.
Overall Number of Participants Analyzed	488	487	330
Mean (Standard Deviation); Unit of Measure: units on a scale
	-0.33 (0.51)	-0.65 (0.59)	-0.56 (0.54)

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 composite score of 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 using visual analog scale (VAS) (participant global VAS). DAS28 was calculated using 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 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Baricitinib	Adalimumab
Arm/Group Description:	Placebo administered orally once daily through Week 24 and placebo administered by SC injection every 2 weeks through Week 50. At Week 24, participants were switched to baricitinib 4 mg orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally daily through Week 52. Participants continued to take background MTX therapy throughout study.	Baricitinib 4 mg administered orally once daily through Week 52 and an adalimumab placebo SC injection every 2 weeks through Week 50. Starting at Week 16, nonresponder participants originally randomized to baricitinib continued to receive baricitinib 4 mg administered orally once daily through Week 52. Participants continued to take background MTX therapy throughout study. .	Adalimumab 40 mg administered by SC injection every 2 weeks through Week 50 and baricitinib placebo orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.
Overall Number of Participants Analyzed	488	487	330
Mean (Standard Deviation); Unit of Measure: units on a scale
	-1.01 (1.12)	-2.27 (1.22)	-1.98 (1.28)

5. Secondary Outcome

Title	Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response
Description	ACR50 and ACR70 Responder Index is a composite of clinical, laboratory, and functional measures in RA. ACR50 and ACR70 Responder is a participant who has at least 50% or 70% improvement, respectively, 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 the study drug. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.

Arm/Group Title	Placebo	Baricitinib	Adalimumab
Arm/Group Description:	Placebo administered orally once daily through Week 24 and placebo administered by SC injection every 2 weeks through Week 50. At Week 24, participants were switched to baricitinib 4 mg orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally daily through Week 52. Participants continued to take background MTX therapy throughout study.	Baricitinib 4 mg administered orally once daily through Week 52 and an adalimumab placebo SC injection every 2 weeks through Week 50. Starting at Week 16, nonresponder participants originally randomized to baricitinib continued to receive baricitinib 4 mg administered orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.	Adalimumab 40 mg administered by SC injection every 2 weeks through Week 50 and baricitinib placebo orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.
Overall Number of Participants Analyzed	488	487	330
Measure Type: Number; Unit of Measure: percentage of participants
ACR50 Week 12	16.8	45.0	34.8
ACR50 Week 24	19.3	50.5	45.5
ACR50 Week 52	NA [1]	55.9	47.0
ACR70 Week 12	4.7	18.9	12.7
ACR70 Week 24	8.0	29.8	21.8
ACR70 Week 52	NA [1]	37.2	30.6

[1]

No data available. There is no Placebo Arm at week 52.

6. 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 12, Week 24, Week 52

Outcome Measure Data

Analysis Population Description

mITT population: all randomized participants who received at least 1 dose of the 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	Placebo	Baricitinib	Adalimumab
Arm/Group Description:	Placebo administered orally once daily through Week 24 and placebo administered by SC injection every 2 weeks through Week 50. At Week 24, participants were switched to baricitinib 4 mg orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally daily through Week 52. Participants continued to take background MTX therapy throughout study.	Baricitinib 4 mg administered orally once daily through Week 52 and an adalimumab placebo SC injection every 2 weeks through Week 50. Starting at Week 16, nonresponder participants originally randomized to baricitinib continued to receive baricitinib 4 mg administered orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.	Adalimumab 40 mg administered by SC injection every 2 weeks through Week 50 and baricitinib placebo orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.
Overall Number of Participants Analyzed	481	478	324
Mean (Standard Deviation); Unit of Measure: units on a scale
Week 12	-13.53 (13.88)	-23.00 (12.66)	-20.42 (13.47)
Week 24	-14.21 (15.13)	-25.04 (13.61)	-22.92 (14.63)
Week 52	NA [1] (NA)	-26.44 (14.42)	-23.48 (15.28)

[1]

NA= No data available. There is no Placebo Arm at week 52.

7. Secondary Outcome

Title	Percentage of Participants Achieving 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 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	Placebo	Baricitinib	Adalimumab
Arm/Group Description:	Placebo administered orally once daily through Week 24 and placebo administered by SC injection every 2 weeks through Week 50. At Week 24, participants were switched to baricitinib 4 mg orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally daily through Week 52. Participants continued to take background MTX therapy throughout study.	Baricitinib 4 mg administered orally once daily through Week 52 and an adalimumab placebo SC injection every 2 weeks through Week 50. Starting at Week 16, nonresponder participants originally randomized to baricitinib continued to receive baricitinib 4 mg administered orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.	Adalimumab 40 mg administered by SC injection every 2 weeks through Week 50 and baricitinib placebo orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.
Overall Number of Participants Analyzed	488	487	330
Measure Type: Number; Unit of Measure: percentage of participants
Week 12	1.8	8.4	7.3
Week 24	3.1	16.0	13.6
Week 52	NA [1]	22.6	17.9

[1]

NA= No data available. There is no Placebo Arm at week 52.

8. Secondary Outcome

Title	Percentage of Participants Achieving American College of Rheumatology European League Against Rheumatism (ACR/EULAR) Remission - Boolean Remission
Description	The ACR/EULAR definitions of RA remission includes 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	Placebo	Baricitinib	Adalimumab
Arm/Group Description:	Placebo administered orally once daily through Week 24 and placebo administered by SC injection every 2 weeks through Week 50. At Week 24, participants were switched to baricitinib 4 mg orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally daily through Week 52. Participants continued to take background MTX therapy throughout study.	Baricitinib 4 mg administered orally once daily through Week 52 and an adalimumab placebo SC injection every 2 weeks through Week 50. Starting at Week 16, nonresponder participants originally randomized to baricitinib continued to receive baricitinib 4 mg administered orally once daily through Week 52. Participants continued to take background MTX therapy throughout study. Baricitinib: Administered orally	Adalimumab 40 mg administered by SC injection every 2 weeks through Week 50 and baricitinib placebo orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.
Overall Number of Participants Analyzed	488	487	330
Measure Type: Number; Unit of Measure: percentage of participants
Week 12	1.0	7.2	5.2
Week 24	2.7	12.1	10.0
Week 52	NA [1]	15.6	13.0

[1]

NA= No data available. There is no Placebo Arm at week 52.

9. Secondary Outcome

Title	Median of Individual Participant Mean Duration of Morning Joint Stiffness in the Prior 7 Days as Collected in Electronic Diaries
Description	Participants recorded the duration of their morning joint stiffness (MJS) in hours and minutes into electronic diaries daily. If morning joint stiffness duration was longer than 12 hours (720 minutes), it was truncated to 720 minutes for statistical presentations and analyses. The average value across the 7 days preceding each visit was calculated. A decrease in duration of morning joint stiffness indicated an improvement in the participant's condition.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

mITT population: all randomized participants who received at least 1 dose of the study drug and had at least 4 entries within any post-baseline 7-day window are included in the analysis.

Arm/Group Title	Placebo	Baricitinib	Adalimumab
Arm/Group Description:	Placebo administered orally once daily through Week 24 and placebo administered by SC injection every 2 weeks through Week 50. At Week 24, participants were switched to baricitinib 4 mg orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally daily through Week 52. Participants continued to take background MTX therapy throughout study.	Baricitinib 4 mg administered orally once daily through Week 52 and an adalimumab placebo SC injection every 2 weeks through Week 50. Starting at Week 16, nonresponder participants originally randomized to baricitinib continued to receive baricitinib 4 mg administered orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.	Adalimumab 40 mg administered by SC injection every 2 weeks through Week 50 and baricitinib placebo orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.
Overall Number of Participants Analyzed	479	479	323
Median (95% Confidence Interval); Unit of Measure: Minutes
	60.0; (60.0 to 75.0)	27.1; (20.0 to 30.0)	36.6; (30.0 to 45.7)

10. Secondary Outcome

Title	Mean Severity of Morning Joint Stiffness Numeric Rating Scale (NRS) in the Prior 7 Days as Collected in Electronic Diaries
Description	Participants rated the severity of their morning joint stiffness by selecting a number from 0 to 10 that best described their overall level of morning joint stiffness from the time they woke up, where 0 represents "no joint stiffness" and 10 represents "joint stiffness as bad as you can imagine". Participants reported their severity daily in electronic diaries. The average value across the 7 days preceding each visit was calculated.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

mITT population: all randomized participants who received at least 1 dose of the study drug and had at least 4 entries within any post-baseline 7-day window are included in the analysis.

Arm/Group Title	Placebo	Baricitinib	Adalimumab
Arm/Group Description:	Placebo administered orally once daily through Week 24 and placebo administered by SC injection every 2 weeks through Week 50. At Week 24, participants were switched to baricitinib 4 mg orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally daily through Week 52. Participants continued to take background MTX therapy throughout study.	Baricitinib 4 mg administered orally once daily through Week 52 and an adalimumab placebo SC injection every 2 weeks through Week 50. Starting at Week 16, nonresponder participants originally randomized to baricitinib continued to receive baricitinib 4 mg administered orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.	Adalimumab 40 mg administered by SC injection every 2 weeks through Week 50 and baricitinib placebo orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.
Overall Number of Participants Analyzed	479	479	323
Mean (Standard Deviation); Unit of Measure: units on a scale
	4.1 (2.3)	3.0 (2.2)	3.4 (2.3)

11. Secondary Outcome

Title	Mean Worst Tiredness Numeric Rating Scale (NRS) in the Prior 7 Days as Collected in Electronic Diaries
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". Participants reported their worst tiredness in electronic diaries. The average value across the 7 days preceding each visit is calculated.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

mITT population: all randomized participants who received at least 1 dose of the study drug and had at least 4 entries within any post-baseline 7-day window are included in the analysis.

Arm/Group Title	Placebo	Baricitinib	Adalimumab
Arm/Group Description:	Placebo administered orally once daily through Week 24 and placebo administered by SC injection every 2 weeks through Week 50. At Week 24, participants were switched to baricitinib 4 mg orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally daily through Week 52. Participants continued to take background MTX therapy throughout study.	Baricitinib 4 mg administered orally once daily through Week 52 and an adalimumab placebo SC injection every 2 weeks through Week 50. Starting at Week 16, nonresponder participants originally randomized to baricitinib continued to receive baricitinib 4 mg administered orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.	Adalimumab 40 mg administered by SC injection every 2 weeks through Week 50 and baricitinib placebo orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.
Overall Number of Participants Analyzed	479	479	323
Mean (Standard Deviation); Unit of Measure: units on a scale
	4.4 (2.3)	3.6 (2.2)	3.9 (2.3)

12. Secondary Outcome

Title	Mean Worst Joint Pain NRS in the Prior 7 Days as Collected in Electronic Diaries
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". Participants reported their worst joint pain in daily electronic diaries. The average value across the 7 days preceding each visit was calculated.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

mITT population: all randomized participants who received at least 1 dose of the study drug and had at least 4 entries within any post-baseline 7-day window are included in the analysis.

Arm/Group Title	Placebo	Baricitinib	Adalimumab
Arm/Group Description:	Placebo administered orally once daily through Week 24 and placebo administered by SC injection every 2 weeks through Week 50. At Week 24, participants were switched to baricitinib 4 mg orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally daily through Week 52. Participants continued to take background MTX therapy throughout study.	Baricitinib 4 mg administered orally once daily through Week 52 and an adalimumab placebo SC injection every 2 weeks through Week 50. Starting at Week 16, nonresponder participants originally randomized to baricitinib continued to receive baricitinib 4 mg administered orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.	Adalimumab 40 mg administered by SC injection every 2 weeks through Week 50 and baricitinib placebo orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.
Overall Number of Participants Analyzed	479	479	323
Mean (Standard Deviation); Unit of Measure: units on a scale
	4.6 (2.2)	3.4 (2.2)	4.0 (2.3)

13. Secondary Outcome

Title	Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale Scores
Description	The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale is a brief 13-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 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, 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	Placebo	Baricitinib	Adalimumab
Arm/Group Description:	Placebo administered orally once daily through Week 24 and placebo administered by SC injection every 2 weeks through Week 50. At Week 24, participants were switched to baricitinib 4 mg orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally daily through Week 52. Participants continued to take background MTX therapy throughout study.	Baricitinib 4 mg administered orally once daily through Week 52 and an adalimumab placebo SC injection every 2 weeks through Week 50. Starting at Week 16, nonresponder participants originally randomized to baricitinib continued to receive baricitinib 4 mg administered orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.	Adalimumab 40 mg administered by SC injection every 2 weeks through Week 50 and baricitinib placebo orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.
Overall Number of Participants Analyzed	475	479	320
Mean (Standard Deviation); Unit of Measure: units on a scale
Week 12	6.8 (9.9)	9.6 (10.4)	9.5 (10.1)
Week 24	6.6 (10.4)	10.4 (10.8)	9.9 (11.2)
Week 52	NA [1] (NA)	10.8 (10.9)	9.8 (10.8)

[1]

NA= No data available. There is no Placebo Arm at week 52.

14. Secondary Outcome

Title	Change From Baseline in Mental Component Score (MCS), 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 (mental [MCS] and physical [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 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, 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	Placebo	Baricitinib	Adalimumab
Arm/Group Description:	Placebo administered orally once daily through Week 24 and placebo administered by SC injection every 2 weeks through Week 50. At Week 24, participants were switched to baricitinib 4 mg orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally daily through Week 52. Participants continued to take background MTX therapy throughout study.	Baricitinib 4 mg administered orally once daily through Week 52 and an adalimumab placebo SC injection every 2 weeks through Week 50. Starting at Week 16, nonresponder participants originally randomized to baricitinib continued to receive baricitinib 4 mg administered orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.	Adalimumab 40 mg administered by SC injection every 2 weeks through Week 50 and baricitinib placebo orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.
Overall Number of Participants Analyzed	475	479	320
Mean (Standard Deviation); Unit of Measure: units on a scale
MCS Week 12	3.2 (10.3)	3.3 (10.5)	3.8 (10.8)
MCS Week 24	2.2 (11.4)	3.8 (10.9)	3.9 (11.6)
MCS Week 52	NA [1] (NA)	4.0 (10.8)	3.7 (11.2)
PCS Week 12	4.3 (7.1)	8.9 (8.1)	7.6 (8.2)
PCS Week 24	4.6 (7.8)	9.9 (8.2)	8.3 (9.1)
PCS Week 52	NA [1] (NA)	10.4 (9.0)	9.0 (9.2)

[1]

No data available. There is no Placebo Arm at week 52.

15. 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 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, 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	Placebo	Baricitinib	Adalimumab
Arm/Group Description:	Placebo administered orally once daily through Week 24 and placebo administered by SC injection every 2 weeks through Week 50. At Week 24, participants were switched to baricitinib 4 mg orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally daily through Week 52. Participants continued to take background MTX therapy throughout study.	Baricitinib 4 mg administered orally once daily through Week 52 and an adalimumab placebo SC injection every 2 weeks through Week 50. Starting at Week 16, nonresponder participants originally randomized to baricitinib continued to receive baricitinib 4 mg administered orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.	Adalimumab 40 mg administered by SC injection every 2 weeks through Week 50 and baricitinib placebo orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.
Overall Number of Participants Analyzed	475	479	320
Mean (Standard Deviation); Unit of Measure: units on a scale
Index Score (US Algorithm) Week 12	0.073 (0.151)	0.132 (0.156)	0.130 (0.159)
Index Score (US Algorithm) Week 24	0.065 (0.168)	0.143 (0.168)	0.137 (0.167)
Index Score (US Algorithm) Week 52	NA [1] (NA)	0.152 (0.163)	0.141 (0.189)
Index Score (UK Algorithm) Week 12	0.107 (0.221)	0.188 (0.228)	0.186 (0.232)
Index Score (UK Algorithm) Week 24	0.094 (0.247)	0.203 (0.244)	0.195 (0.245)
Index Score (UK Algorithm) Week 52	NA [1] (NA)	0.215 (0.235)	0.198 (0.273)

[1]

NA= No data available. There is no Placebo Arm at week 52.

16. 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 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, 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	Placebo	Baricitinib	Adalimumab
Arm/Group Description:	Placebo administered orally once daily through Week 24 and placebo administered by SC injection every 2 weeks through Week 50. At Week 24, participants were switched to baricitinib 4 mg orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally daily through Week 52. Participants continued to take background MTX therapy throughout study.	Baricitinib 4 mg administered orally once daily through Week 52 and an adalimumab placebo SC injection every 2 weeks through Week 50. Starting at Week 16, nonresponder participants originally randomized to baricitinib continued to receive baricitinib 4 mg administered orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.	Adalimumab 40 mg administered by SC injection every 2 weeks through Week 50 and baricitinib placebo orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.
Overall Number of Participants Analyzed	475	479	320
Mean (Standard Deviation); Unit of Measure: millimeter
Self-Perceived Health Week 12	7.9 (26.2)	14.9 (25.8)	10.7 (26.9)
Self-Perceived Health Week 24	5.6 (27.1)	17.5 (28.3)	12.6 (28.9)
Self-Perceived Health Week 52	NA [1] (NA)	19.9 (28.0)	13.3 (29.7)

[1]

NA= No data available. There is no Placebo Arm at week 52.

17. 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 12, Week 24, Week 52

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Baricitinib	Adalimumab
Arm/Group Description:	Placebo administered orally once daily through Week 24 and placebo administered by SC injection every 2 weeks through Week 50. At Week 24, participants were switched to baricitinib 4 mg orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally daily through Week 52. Participants continued to take background MTX therapy throughout study.	Baricitinib 4 mg administered orally once daily through Week 52 and an adalimumab placebo SC injection every 2 weeks through Week 50. Starting at Week 16, nonresponder participants originally randomized to baricitinib continued to receive baricitinib 4 mg administered orally once daily through Week 52. Participants continued to take background MTX therapy throughout study. Baricitinib: Administered orally	Adalimumab 40 mg administered by SC injection every 2 weeks through Week 50 and baricitinib placebo orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.
Overall Number of Participants Analyzed	458	474	315
Mean (Standard Deviation); Unit of Measure: percentage of impairment
Absenteeism Week 12 (n=160,168,118)	0.5 (27.7)	-4.9 (20.6)	-0.5 (25.7)
Absenteeism Week 24 (n=118,139,102)	-1.6 (24.5)	-1.8 (25.2)	-3.2 (23.8)
Absenteeism Week 52 (n=0,124,92)	NA [1] (NA)	-3.8 (25.1)	-3.7 (24.3)
Presenteeism Week 12 (n=147,160,113)	-11 (23)	-21 (26)	-16 (24)
Presenteeism Week 24 (n=110,134,99)	-11 (22)	-23 (27)	-22 (26)
Presenteeism Week 52 (n=0,119,88)	NA [1] (NA)	-25 (27)	-25 (27)
Work Productivity Loss Week 12 (n=147,160,113)	-10.4 (24.3)	-21.6 (28.0)	-14.0 (25.6)
Work Productivity Loss Week 24 (n=110,134,99)	-9.0 (24.9)	-22.1 (30.2)	-21.4 (27.2)
Work Productivity Loss Week 52 (n=0,119,88)	NA [1] (NA)	-24.4 (30.1)	-24.6 (29.8)
Activity Impairment Week 12 (n=458,474,315)	-11 (25)	-25 (26)	-20 (25)
Activity Impairment Week 24 (n=333,430,272)	-16 (26)	-28 (27)	-26 (26)
Activity Impairment Week 52 (n=0,396,240)	NA [1] (NA)	-30 (27)	-28 (27)

[1]

NA= No data available. There is no Placebo Arm at week 52.

18. Secondary Outcome

Title	Change From Baseline in Joint Space Narrowing (JSN) 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, 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	Placebo	Baricitinib	Adalimumab
Arm/Group Description:	Placebo administered orally once daily through Week 24 and placebo administered by SC injection every 2 weeks through Week 50. At Week 24, participants were switched to baricitinib 4 mg orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally daily through Week 52. Participants continued to take background MTX therapy throughout study.	Baricitinib 4 mg administered orally once daily through Week 52 and an adalimumab placebo SC injection every 2 weeks through Week 50. Starting at Week 16, nonresponder participants originally randomized to baricitinib continued to receive baricitinib 4 mg administered orally once daily through Week 52. Participants continued to take background MTX therapy throughout study. Baricitinib: Administered orally	Adalimumab 40 mg administered by SC injection every 2 weeks through Week 50 and baricitinib placebo orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily through Week 52. Participants continued to take background MTX therapy throughout study.
Overall Number of Participants Analyzed	452	473	312
Mean (Standard Deviation); Unit of Measure: units on a scale
Joint Space Narrowing Week 24 (n= 452, 470, 312)	0.27 (1.15)	0.10 (0.74)	0.09 (0.52)
Joint Space Narrowing Week 52 (n= 452, 473, 312)	0.56 (2.33)	0.18 (1.02)	0.17 (1.00)
Bone Erosion Score Week 24 (n=452, 470, 312)	0.57 (1.58)	0.25 (1.12)	0.20 (1.08)
Bone Erosion Score Week 52 (n= 452, 473, 312)	1.15 (3.21)	0.42 (1.91)	0.34 (2.00)

19. 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 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
Overall Number of Participants Analyzed	635
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nanomole/Liter (nmol/L)
	143; (19.7%)

20. 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 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
Overall Number of Participants Analyzed	635
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nanomole*hr/Liter (nmol*hr/L)
	1220; (45.8%)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	All enrolled participants including rescue therapy. After Week 16, rescue therapy will be offered at the discretion of the investigator based on tender joint count and swollen joint count.
Arm/Group Title	Placebo Treatment A		Baricitinib Treatment A		Adalimumab Treatment A		Placebo Treatment B		BaricitinibTreatment B		Adalimumab Treatment B		Rescue		Placebo Follow-up		Baricitinib Follow-up		Adalimumab Follow-up
Arm/Group Description	Placebo Treatment A (week 0-24). Placebo administered orally (PO) once daily (QD) through Week 24 and placebo administered by subcutaneous (SC) injection every 2 weeks through Week 50. At Week 24, participants were given baricitinib 4 milligram (mg) orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily through Week 52.		Baricitinib Treatment A (week 0-24). Baricitinib 4 mg administered orally once daily through Week 52 and an adalimumab placebo SC injection every 2 weeks through Week 50. Starting at Week 16, nonresponder participants originally randomized to baricitinib continued to receive baricitinib 4 mg administered orally once daily through Week 52.		Adalimumab Treatment A (week 0-24). Adalimumab 40 mg administered by SC injection every 2 weeks through Week 50 and baricitinib placebo orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily through Week 52.		Placebo Treatment B (week 24-52). Placebo administered orally (PO) once daily (QD) through Week 24 and placebo administered by subcutaneous (SC) injection every 2 weeks through Week 50. At Week 24, participants were given baricitinib 4 milligram (mg) orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily through Week 52.		Baricitinib Treatment B (week 24-52). Baricitinib 4 mg administered orally once daily through Week 52 and an adalimumab placebo SC injection every 2 weeks through Week 50. Starting at Week 16, nonresponder participants originally randomized to baricitinib continued to receive baricitinib 4 mg administered orally once daily through Week 52.		Adalimumab Treatment B (week 24-52). Adalimumab 40 mg administered by SC injection every 2 weeks through Week 50 and baricitinib placebo orally once daily through Week 52. Starting at Week 16, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily through Week 52.		Baricitinib 4 mg administered PO QD through Week 52 (Week 16-52).		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. Participants who were rescued or switched to Baricitinib 4 mg.		No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug.
All-Cause Mortality
	Placebo Treatment A		Baricitinib Treatment A		Adalimumab Treatment A		Placebo Treatment B		BaricitinibTreatment B		Adalimumab Treatment B		Rescue		Placebo Follow-up		Baricitinib Follow-up		Adalimumab Follow-up
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--		--/--		--/--		--/--		--/--		--/--		--/--		--/--
Serious Adverse Events
	Placebo Treatment A		Baricitinib Treatment A		Adalimumab Treatment A		Placebo Treatment B		BaricitinibTreatment B		Adalimumab Treatment B		Rescue		Placebo Follow-up		Baricitinib Follow-up		Adalimumab 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	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/488 (5.33%)		26/487 (5.34%)		7/330 (2.12%)		12/306 (3.92%)		16/424 (3.77%)		9/267 (3.37%)		17/227 (7.49%)		2/33 (6.06%)		0/76 (0.00%)		0/20 (0.00%)
Blood and lymphatic system disorders
Anaemia † 1	0/488 (0.00%)	0	2/487 (0.41%)	2	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	2/227 (0.88%)	2	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Lymphocytosis † 1	0/488 (0.00%)	0	1/487 (0.21%)	1	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Neutropenia † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	1/424 (0.24%)	1	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Cardiac disorders
Cardiac failure † 1	1/488 (0.20%)	1	1/487 (0.21%)	1	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Myocardial infarction † 1	0/488 (0.00%)	0	1/487 (0.21%)	1	0/330 (0.00%)	0	0/306 (0.00%)	0	1/424 (0.24%)	1	1/267 (0.37%)	1	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Sinus bradycardia † 1	0/488 (0.00%)	0	1/487 (0.21%)	1	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Acute myocardial infarction † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	1/424 (0.24%)	1	0/267 (0.00%)	0	1/227 (0.44%)	1	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Supraventricular tachycardia † 1	1/488 (0.20%)	1	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Eye disorders
Cataract † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	1/330 (0.30%)	1	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Macular fibrosis † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	1/267 (0.37%)	1	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Retinal detachment † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	1/267 (0.37%)	1	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Glaucoma † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	1/227 (0.44%)	1	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Gastrointestinal disorders
Duodenal ulcer haemorrhage † 1	0/488 (0.00%)	0	1/487 (0.21%)	1	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Gastric ulcer † 1	0/488 (0.00%)	0	1/487 (0.21%)	1	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Gastrointestinal haemorrhage † 1	1/488 (0.20%)	1	0/487 (0.00%)	0	0/330 (0.00%)	0	1/306 (0.33%)	1	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Large intestine polyp † 1	1/488 (0.20%)	1	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Pancreatitis acute † 1	1/488 (0.20%)	1	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Diarrhoea † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	1/424 (0.24%)	1	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Jejunal ulcer † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	1/424 (0.24%)	1	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Enterocolitis † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	2/227 (0.88%)	2	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Inguinal hernia † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	1/227 (0.44%)	1	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
General disorders
Non-cardiac chest pain † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	1/227 (0.44%)	1	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Hepatobiliary disorders
Bile duct stone † 1	2/488 (0.41%)	2	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Cholangitis sclerosing † 1	1/488 (0.20%)	1	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Cholelithiasis † 1	1/488 (0.20%)	1	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	1/227 (0.44%)	1	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Drug-induced liver injury † 1	0/488 (0.00%)	0	1/487 (0.21%)	1	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Infections and infestations
Arthritis infective † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	1/330 (0.30%)	1	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Bronchitis † 1	1/488 (0.20%)	1	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Cellulitis † 1	0/488 (0.00%)	0	2/487 (0.41%)	2	0/330 (0.00%)	0	0/306 (0.00%)	0	1/424 (0.24%)	1	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Disseminated tuberculosis † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	1/330 (0.30%)	1	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Epiglottitis † 1	0/488 (0.00%)	0	1/487 (0.21%)	1	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Gastroenteritis † 1	2/488 (0.41%)	2	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Herpes zoster † 1	0/488 (0.00%)	0	2/487 (0.41%)	2	0/330 (0.00%)	0	1/306 (0.33%)	1	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Kidney infection † 1	1/488 (0.20%)	1	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Muscle abscess † 1	1/488 (0.20%)	1	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Pneumonia † 1	0/488 (0.00%)	0	1/487 (0.21%)	1	0/330 (0.00%)	0	1/306 (0.33%)	1	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	1/33 (3.03%)	1	0/76 (0.00%)	0	0/20 (0.00%)	0
Pyelonephritis † 1	1/488 (0.20%)	1	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Urinary tract infection † 1	1/488 (0.20%)	1	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	2/424 (0.47%)	2	0/267 (0.00%)	0	1/227 (0.44%)	1	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Atypical pneumonia † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	1/424 (0.24%)	1	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Bacteraemia † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	1/424 (0.24%)	1	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Cholecystitis infective † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	1/267 (0.37%)	1	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Cystitis † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	1/306 (0.33%)	1	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Escherichia sepsis † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	1/267 (0.37%)	1	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Necrotising fasciitis † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	1/424 (0.24%)	1	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Pneumonia pseudomonal † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	1/267 (0.37%)	1	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Pyelonephritis acute † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	1/306 (0.33%)	1	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Viral infection † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	1/306 (0.33%)	1	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Arthritis bacterial † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	1/227 (0.44%)	1	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Sepsis † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	1/227 (0.44%)	1	1/33 (3.03%)	1	0/76 (0.00%)	0	0/20 (0.00%)	0
Soft tissue infection † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	1/227 (0.44%)	1	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Tuberculosis † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	1/227 (0.44%)	1	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Injury, poisoning and procedural complications
Ankle fracture † 1	0/488 (0.00%)	0	1/487 (0.21%)	1	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Femoral neck fracture † 1	0/488 (0.00%)	0	1/487 (0.21%)	1	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Humerus fracture † 1	0/488 (0.00%)	0	1/487 (0.21%)	1	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Joint injury † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	1/330 (0.30%)	1	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Ulna fracture † 1	0/488 (0.00%)	0	1/487 (0.21%)	1	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Fall † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	2/306 (0.65%)	2	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Femur fracture † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	1/306 (0.33%)	1	1/424 (0.24%)	1	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Laceration † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	1/306 (0.33%)	1	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Post concussion syndrome † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	1/306 (0.33%)	1	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Radius fracture † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	1/306 (0.33%)	1	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Road traffic accident † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	1/306 (0.33%)	1	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Spinal compression fracture † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	1/424 (0.24%)	1	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Spinal fracture † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	1/306 (0.33%)	1	0/424 (0.00%)	0	0/267 (0.00%)	0	1/227 (0.44%)	1	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	0/488 (0.00%)	0	1/487 (0.21%)	1	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Aspartate aminotransferase increased † 1	0/488 (0.00%)	0	1/487 (0.21%)	1	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Metabolism and nutrition disorders
Dehydration † 1	1/488 (0.20%)	1	0/487 (0.00%)	0	0/330 (0.00%)	0	1/306 (0.33%)	1	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Diabetes mellitus † 1	1/488 (0.20%)	1	1/487 (0.21%)	1	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Hypoproteinaemia † 1	1/488 (0.20%)	1	0/487 (0.00%)	0	0/330 (0.00%)	0	1/306 (0.33%)	1	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Diabetes mellitus inadequate control † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	1/227 (0.44%)	1	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	1/330 (0.30%)	1	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Back pain † 1	1/488 (0.20%)	1	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Chondrocalcinosis pyrophosphate † 1	1/488 (0.20%)	1	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Intervertebral disc protrusion † 1	1/488 (0.20%)	1	0/487 (0.00%)	0	0/330 (0.00%)	0	1/306 (0.33%)	1	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Osteoporosis † 1	1/488 (0.20%)	1	1/487 (0.21%)	1	0/330 (0.00%)	0	1/306 (0.33%)	1	1/424 (0.24%)	1	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Rheumatoid arthritis † 1	4/488 (0.82%)	4	1/487 (0.21%)	1	0/330 (0.00%)	0	0/306 (0.00%)	0	1/424 (0.24%)	1	0/267 (0.00%)	0	0/227 (0.00%)	0	1/33 (3.03%)	1	0/76 (0.00%)	0	0/20 (0.00%)	0
Bursitis † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	1/267 (0.37%)	1	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Myositis † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	1/306 (0.33%)	1	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Osteoarthritis † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	1/227 (0.44%)	1	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer † 1	0/488 (0.00%)	0	1/487 (0.21%)	1	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Lung squamous cell carcinoma stage III † 1	0/488 (0.00%)	0	1/487 (0.21%)	1	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Ovarian cancer † 1	1/488 (0.20%)	1	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Uterine leiomyoma † 1	1/488 (0.20%)	1	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Clear cell renal cell carcinoma † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	1/424 (0.24%)	1	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Lymphoproliferative disorder † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	1/227 (0.44%)	1	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Squamous cell carcinoma of lung † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	1/227 (0.44%)	1	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Nervous system disorders
Transient ischaemic attack † 1	1/488 (0.20%)	1	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Cerebrovascular accident † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	1/227 (0.44%)	1	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Psychiatric disorders
Insomnia † 1	1/488 (0.20%)	1	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Confusional state † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	1/306 (0.33%)	1	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Generalised anxiety disorder † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	1/424 (0.24%)	1	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Renal and urinary disorders
Acute kidney injury † 1	1/488 (0.20%)	1	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Calculus urinary † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	1/330 (0.30%)	1	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Nephrosclerosis † 1	1/488 (0.20%)	1	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	1/227 (0.44%)	1	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Renal impairment † 1	1/488 (0.20%)	1	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Reproductive system and breast disorders
Metrorrhagia † 1	0/488 (0.00%)	0	1/487 (0.21%)	1	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease † 1	0/488 (0.00%)	0	1/487 (0.21%)	1	1/330 (0.30%)	1	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Interstitial lung disease † 1	0/488 (0.00%)	0	1/487 (0.21%)	1	0/330 (0.00%)	0	1/306 (0.33%)	1	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Nasal septum perforation † 1	1/488 (0.20%)	1	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Acute respiratory failure † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	1/267 (0.37%)	1	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Pleurisy † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	1/267 (0.37%)	1	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Pneumonia aspiration † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	1/424 (0.24%)	1	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Pneumonitis † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	1/424 (0.24%)	1	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Respiratory failure † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	1/33 (3.03%)	1	0/76 (0.00%)	0	0/20 (0.00%)	0
Skin and subcutaneous tissue disorders
Dermatitis allergic † 1	0/488 (0.00%)	0	1/487 (0.21%)	1	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Surgical and medical procedures
Hysterectomy † 1	1/488 (0.20%)	1	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Bladder repair † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	1/306 (0.33%)	1	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Fracture treatment † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	1/306 (0.33%)	1	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Knee arthroplasty † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	1/306 (0.33%)	1	0/424 (0.00%)	0	1/267 (0.37%)	1	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Vascular disorders
Circulatory collapse † 1	0/488 (0.00%)	0	1/487 (0.21%)	1	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Hypotension † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	1/330 (0.30%)	1	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Thrombophlebitis † 1	0/488 (0.00%)	0	1/487 (0.21%)	1	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (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%
	Placebo Treatment A		Baricitinib Treatment A		Adalimumab Treatment A		Placebo Treatment B		BaricitinibTreatment B		Adalimumab Treatment B		Rescue		Placebo Follow-up		Baricitinib Follow-up		Adalimumab 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	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	177/488 (36.27%)		196/487 (40.25%)		132/330 (40.00%)		58/306 (18.95%)		70/424 (16.51%)		38/267 (14.23%)		46/227 (20.26%)		3/33 (9.09%)		0/76 (0.00%)		3/20 (15.00%)
Blood and lymphatic system disorders
Anaemia † 1	15/488 (3.07%)	16	16/487 (3.29%)	16	4/330 (1.21%)	4	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	8/227 (3.52%)	9	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Eye disorders
Blepharitis † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)		1/33 (3.03%)	1	0/76 (0.00%)	0	0/20 (0.00%)	0
Gastrointestinal disorders
Diarrhoea † 1	14/488 (2.87%)	16	11/487 (2.26%)	12	8/330 (2.42%)	10	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Dyspepsia † 1	7/488 (1.43%)	7	9/487 (1.85%)	9	8/330 (2.42%)	8	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Nausea † 1	6/488 (1.23%)	7	14/487 (2.87%)	15	9/330 (2.73%)	9	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Constipation † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	5/227 (2.20%)	6	1/33 (3.03%)	1	0/76 (0.00%)	0	0/20 (0.00%)	0
Infections and infestations
Bronchitis † 1	14/488 (2.87%)	14	19/487 (3.90%)	22	8/330 (2.42%)	8	11/306 (3.59%)	12	12/424 (2.83%)	12	5/267 (1.87%)	5	6/227 (2.64%)	7	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Influenza † 1	4/488 (0.82%)	5	12/487 (2.46%)	12	5/330 (1.52%)	5	3/306 (0.98%)	3	10/424 (2.36%)	10	1/267 (0.37%)	1	5/227 (2.20%)	5	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Nasopharyngitis † 1	35/488 (7.17%)	39	37/487 (7.60%)	41	34/330 (10.30%)	40	15/306 (4.90%)	19	24/424 (5.66%)	26	14/267 (5.24%)	15	9/227 (3.96%)	11	2/33 (6.06%)	2	0/76 (0.00%)	0	0/20 (0.00%)	0
Pharyngitis † 1	14/488 (2.87%)	14	12/487 (2.46%)	13	12/330 (3.64%)	12	10/306 (3.27%)	12	4/424 (0.94%)	4	7/267 (2.62%)	7	5/227 (2.20%)	10	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Upper respiratory tract infection † 1	14/488 (2.87%)	15	15/487 (3.08%)	17	13/330 (3.94%)	16	10/306 (3.27%)	10	13/424 (3.07%)	13	4/267 (1.50%)	4	6/227 (2.64%)	7	0/33 (0.00%)	0	0/76 (0.00%)	0	2/20 (10.00%)	2
Urinary tract infection † 1	16/488 (3.28%)	16	21/487 (4.31%)	25	13/330 (3.94%)	14	5/306 (1.63%)	5	10/424 (2.36%)	10	5/267 (1.87%)	6	5/227 (2.20%)	6	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	5/488 (1.02%)	5	8/487 (1.64%)	9	9/330 (2.73%)	9	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Blood creatine phosphokinase increased † 1	3/488 (0.61%)	3	13/487 (2.67%)	15	2/330 (0.61%)	2	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	5/227 (2.20%)	5	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Metabolism and nutrition disorders
Hypercholesterolaemia † 1	7/488 (1.43%)	7	15/487 (3.08%)	15	2/330 (0.61%)	2	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Hyperlipidaemia † 1	2/488 (0.41%)	2	10/487 (2.05%)	11	3/330 (0.91%)	3	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Musculoskeletal and connective tissue disorders
Back pain † 1	8/488 (1.64%)	8	9/487 (1.85%)	9	10/330 (3.03%)	13	7/306 (2.29%)	7	9/424 (2.12%)	9	4/267 (1.50%)	4	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Rheumatoid arthritis † 1	14/488 (2.87%)	15	5/487 (1.03%)	6	4/330 (1.21%)	5	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Nervous system disorders
Headache † 1	12/488 (2.46%)	12	14/487 (2.87%)	17	13/330 (3.94%)	16	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Reproductive system and breast disorders
Erectile dysfunction † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	2/79 (2.53%)	2	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Benign prostatic hyperplasia † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	1/47 (2.13%)	1	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Calculus prostatic † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	1/47 (2.13%)	1	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Ovarian cyst † 1	0/488 (0.00%)	0	0/487 (0.00%)	0	0/330 (0.00%)	0	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	1/16 (6.25%)	1
Respiratory, thoracic and mediastinal disorders
Cough † 1	8/488 (1.64%)	9	7/487 (1.44%)	7	7/330 (2.12%)	7	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Skin and subcutaneous tissue disorders
Rash † 1	5/488 (1.02%)	6	3/487 (0.62%)	3	7/330 (2.12%)	7	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (0.00%)	0
Vascular disorders
Hypertension † 1	13/488 (2.66%)	13	9/487 (1.85%)	9	11/330 (3.33%)	11	0/306 (0.00%)	0	0/424 (0.00%)	0	0/267 (0.00%)	0	0/227 (0.00%)	0	0/33 (0.00%)	0	0/76 (0.00%)	0	0/20 (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, 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.

Schlueter M, Finn E, Diaz S, Dilla T, Inciarte-Mundo J, Fakhouri W. Cost-effectiveness analysis of baricitinib versus adalimumab for the treatment of moderate-to-severe rheumatoid arthritis in Spain. Clinicoecon Outcomes Res. 2019 Jun 6;11:395-403. doi: 10.2147/CEOR.S201621. eCollection 2019.

Michaud K, Pope JE, Emery P, Zhu B, Gaich CL, DeLozier AM, Zhang X, Dickson CL, Smolen JS. Relative Impact of Pain and Fatigue on Work Productivity in Patients with Rheumatoid Arthritis from the RA-BEAM Baricitinib Trial. Rheumatol Ther. 2019 Sep;6(3):409-419. doi: 10.1007/s40744-019-0164-4. Epub 2019 Jun 21.

Tanaka Y, Fautrel B, Keystone EC, Ortmann RA, Xie L, Zhu B, Issa M, Patel H, Gaich CL, de Bono S, Rooney TP, Taylor PC. Clinical outcomes in patients switched from adalimumab to baricitinib due to non-response and/or study design: phase III data in patients with rheumatoid arthritis. Ann Rheum Dis. 2019 Jul;78(7):890-898. doi: 10.1136/annrheumdis-2018-214529. Epub 2019 Apr 30.

Bingham CO 3rd, Gaich CL, DeLozier AM, Engstrom KD, Naegeli AN, de Bono S, Banerjee P, Taylor PC. Use of daily electronic patient-reported outcome (PRO) diaries in randomized controlled trials for rheumatoid arthritis: rationale and implementation. Trials. 2019 Mar 22;20(1):182. doi: 10.1186/s13063-019-3272-0. Erratum In: Trials. 2019 Jun 4;20(1):322.

Combe B, Balsa A, Sarzi-Puttini P, Tony HP, de la Torre I, Rogai V, Durand F, Witt S, Zhong J, Dougados M. Efficacy and safety data based on historical or pre-existing conditions at baseline for patients with active rheumatoid arthritis who were treated with baricitinib. Ann Rheum Dis. 2019 Aug;78(8):1135-1138. doi: 10.1136/annrheumdis-2018-214261. Epub 2019 Mar 6. No abstract available.

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.

Tanaka Y, McInnes IB, Taylor PC, Byers NL, Chen L, de Bono S, Issa M, Macias WL, Rogai V, Rooney TP, Schlichting DE, Zuckerman SH, Emery P. Characterization and Changes of Lymphocyte Subsets in Baricitinib-Treated Patients With Rheumatoid Arthritis: An Integrated Analysis. Arthritis Rheumatol. 2018 Dec;70(12):1923-1932. doi: 10.1002/art.40680. Epub 2018 Oct 22.

Wells AF, Greenwald M, Bradley JD, Alam J, Arora V, Kartman CE. Baricitinib in Patients with Rheumatoid Arthritis and an Inadequate Response to Conventional Disease-Modifying Antirheumatic Drugs in United States and Rest of World: A Subset Analysis. Rheumatol Ther. 2018 Jun;5(1):43-55. doi: 10.1007/s40744-018-0110-x. Epub 2018 Apr 21.

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.

Keystone EC, Taylor PC, Tanaka Y, Gaich C, DeLozier AM, Dudek A, Zamora JV, Cobos JAC, Rooney T, Bono S, Arora V, Linetzky B, Weinblatt ME. Patient-reported outcomes from a phase 3 study of baricitinib versus placebo or adalimumab in rheumatoid arthritis: secondary analyses from the RA-BEAM study. Ann Rheum Dis. 2017 Nov;76(11):1853-1861. doi: 10.1136/annrheumdis-2017-211259. Epub 2017 Aug 10.

Taylor PC, Keystone EC, van der Heijde D, Weinblatt ME, Del Carmen Morales L, Reyes Gonzaga J, Yakushin S, Ishii T, Emoto K, Beattie S, Arora V, Gaich C, Rooney T, Schlichting D, Macias WL, de Bono S, Tanaka Y. Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2017 Feb 16;376(7):652-662. doi: 10.1056/NEJMoa1608345.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01710358
• Other Study ID Numbers: 13978; I4V-MC-JADV ( Other Identifier: Eli Lilly and Company )
• First Submitted: October 17, 2012
• First Posted: October 19, 2012
• Results First Submitted: March 10, 2017
• Results First Posted: August 15, 2017
• Last Update Posted: September 18, 2019