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Trial record 45 of 62 for:    Baricitinib

A Moderate to Severe Rheumatoid Arthritis Study (RA-BEACON)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01721044
Recruitment Status : Completed
First Posted : November 2, 2012
Results First Posted : January 18, 2018
Last Update Posted : September 18, 2019
Sponsor:
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: Placebo
Drug: Baricitinib
Drug: cDMARD
Enrollment 527
Recruitment Details  
Pre-assignment Details Participants who did not adequately respond (nonresponders) to study drug were eligible for rescue treatment with baricitinib 4 mg beginning at Week 16. Nonresponders were defined as lack of improvement of at least 20% in both tender joint count and swollen joint count at both Weeks 14 and 16 compared to baseline.
Arm/Group Title Placebo Baricitinib 2 mg Baricitinib 4 mg
Hide Arm/Group Description Placebo administered orally (PO) once daily (QD) through Week 24. Participants continued to take background conventional disease-modifying antirheumatic drug (cDMARD) therapy throughout study. Baricitinib 2 milligram (mg) administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study. Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Period Title: Treatment Period
Started 176 174 [1] 177
Rescue Week 16-24 56 38 33
Completed 144 157 158
Not Completed 32 17 19
Reason Not Completed
Adverse Event             7             7             10
Death             0             0             1
Lack of Efficacy             16             4             4
Lost to Follow-up             0             0             1
Physician Decision             1             0             2
Protocol Violation             1             0             0
Withdrawal by Subject             7             6             1
[1]
Randomized to 4mg (N=11) but received 2mg due to moderate renal impairment were included in 4mg arm
Period Title: Follow Up
Started 19 [1] 9 [1] 20 [2]
Completed 19 9 20
Not Completed 0 0 0
[1]
Participants from treatment who entered the post-treatment follow-up period.
[2]
Participants from treatment and rescue who entered the post-treatment follow-up period.
Arm/Group Title Placebo Baricitinib 2 mg Baricitinib 4 mg Total
Hide Arm/Group Description Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study. Baricitinib 2 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study. Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study. Total of all reporting groups
Overall Number of Baseline Participants 176 174 177 527
Hide Baseline Analysis Population Description
Modified Intent-to-Treat (mITT) population includes all randomized participants who received at least 1 dose of the study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 176 participants 174 participants 177 participants 527 participants
56.0  (10.7) 55.1  (11.1) 55.9  (11.3) 55.7  (11.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 176 participants 174 participants 177 participants 527 participants
Female 145 137 149 431
Male 31 37 28 96
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 176 participants 174 participants 177 participants 527 participants
American Indian or Alaska Native 9 12 11 32
Asian 11 9 12 32
Native Hawaiian or Other Pacific Islander 0 0 0 0
Black or African American 8 9 7 24
White 147 144 144 435
More than one race 1 0 0 1
Unknown or Not Reported 0 0 3 3
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Argentina Number Analyzed 176 participants 174 participants 177 participants 527 participants
9 5 7 21
Australia Number Analyzed 176 participants 174 participants 177 participants 527 participants
8 9 4 21
Austria Number Analyzed 176 participants 174 participants 177 participants 527 participants
5 3 8 16
Belgium Number Analyzed 176 participants 174 participants 177 participants 527 participants
1 1 1 3
Canada Number Analyzed 176 participants 174 participants 177 participants 527 participants
1 4 3 8
Denmark Number Analyzed 176 participants 174 participants 177 participants 527 participants
2 3 1 6
France Number Analyzed 176 participants 174 participants 177 participants 527 participants
7 10 7 24
Germany Number Analyzed 176 participants 174 participants 177 participants 527 participants
8 5 6 19
Greece Number Analyzed 176 participants 174 participants 177 participants 527 participants
4 3 2 9
Israel Number Analyzed 176 participants 174 participants 177 participants 527 participants
9 8 13 30
Italy Number Analyzed 176 participants 174 participants 177 participants 527 participants
2 3 3 8
Japan Number Analyzed 176 participants 174 participants 177 participants 527 participants
6 6 8 20
Mexico Number Analyzed 176 participants 174 participants 177 participants 527 participants
9 12 10 31
Netherlands Number Analyzed 176 participants 174 participants 177 participants 527 participants
0 1 1 2
Poland Number Analyzed 176 participants 174 participants 177 participants 527 participants
10 13 9 32
South Korea Number Analyzed 176 participants 174 participants 177 participants 527 participants
4 3 3 10
Spain Number Analyzed 176 participants 174 participants 177 participants 527 participants
10 7 10 27
Switzerland Number Analyzed 176 participants 174 participants 177 participants 527 participants
1 2 4 7
Turkey Number Analyzed 176 participants 174 participants 177 participants 527 participants
1 1 1 3
United Kingdom Number Analyzed 176 participants 174 participants 177 participants 527 participants
2 1 1 4
United States Number Analyzed 176 participants 174 participants 177 participants 527 participants
77 74 75 226
Duration of Rheumatoid Arthritis   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 176 participants 174 participants 177 participants 527 participants
14.0  (9.6) 13.7  (8.0) 14.3  (9.4) 14.0  (9.0)
[1]
Measure Description: Time from Symptom Onset of Rheumatoid Arthritis
Tender Joint Count of 68 Evaluable Joints   [1] 
Mean (Standard Deviation)
Unit of measure:  Number of Joints
Number Analyzed 174 participants 174 participants 177 participants 525 participants
28.3  (16.4) 31.0  (16.3) 28.1  (15.6) 29.1  (16.1)
[1]
Measure Analysis Population Description: Tender joint count based on 68 joints.
Swollen Joint Count of 66 Evaluable Joints   [1] 
Mean (Standard Deviation)
Unit of measure:  Number of Joints
Number Analyzed 174 participants 174 participants 177 participants 525 participants
17.2  (10.8) 18.6  (12.3) 16.3  (8.9) 17.4  (10.8)
[1]
Measure Analysis Population Description: Swollen joint count based on 66 joints.
High Sensitivity C-Reactive Protein (hsCRP)  
Mean (Standard Deviation)
Unit of measure:  Milligrams/liter (mg/L)
Number Analyzed 176 participants 174 participants 177 participants 527 participants
20.64  (25.26) 19.87  (22.48) 19.76  (24.84) 20.09  (24.19)
1.Primary Outcome
Title Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response - Placebo Versus Baricitinib 4 mg
Hide Description ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis. 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 discontinue study or drug or are rescued before analysis timepoint are deemed non-responders.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat (mITT) population includes all randomized participants who received at least 1 dose of the study drug. Participants will be analyzed according to the study drug to which they were randomized. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using non-responder imputation (NRI).
Arm/Group Title Placebo Baricitinib 4 mg
Hide Arm/Group Description:
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Overall Number of Participants Analyzed 176 177
Measure Type: Number
Unit of Measure: Percentage of Participants
27.3 55.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
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 If logistic regression sample size requirements are not met, the p-value from Fisher's exact test is used instead.
2.Secondary Outcome
Title Change From Baseline in HAQ-DI Score - Placebo Versus Baricitinib 4 mg
Hide Description The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty [0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate 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
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. 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 4 mg
Hide Arm/Group Description:
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Overall Number of Participants Analyzed 176 177
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
-0.20  (0.50) -0.42  (0.49)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
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 ANCOVA
Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in the Disease Activity Score Based on a 28-Joint Count (DAS-28) High Sensitivity C-Reactive Protein (hsCRP) - Placebo Versus Baricitinib 4 mg
Hide Description DAS-28 consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), high sensitivity C-reactive protein (hsCRP) (milligrams per liter), and Patient's Global Assessment of Disease Activity. DAS28 was calculated using following formula: DAS28-hsCRP=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.36*natural log(CRP+1)+0.014*Patient's Global VAS+0.96. Total scores ranged from 1.0-9.4, where lower scores indicated less disease activity.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mBOCF.
Arm/Group Title Placebo Baricitinib 4 mg
Hide Arm/Group Description:
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Overall Number of Participants Analyzed 174 177
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
-0.85  (1.19) -1.81  (1.43)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
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 ANCOVA
Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Remission - Simplified Disease Activity Index (SDAI) ≤3.3 - Placebo Versus Baricitinib 4 mg
Hide Description The ACR/EULAR definitions of rheumatoid arthritis (RA) remission includes an index-based definition. The index-based definition of remission occurs with a SDAI score ≤3.3. The SDAI is a tool for measurement of disease activity in RA that integrates TJC28 (0 to 28), SJC28 (0 to 28), acute phase response using C-reactive protein (0.1 to 10.0 mg/dL), Patient's Global Assessment of Disease Activity using VAS (0 to 10.0 cm), and Physician's Global Assessment of Disease Activity using VAS (0 to 10.0 cm). Lower scores indicated less disease activity.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized or assigned per protocol. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.
Arm/Group Title Placebo Baricitinib 4 mg
Hide Arm/Group Description:
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Overall Number of Participants Analyzed 176 177
Measure Type: Number
Unit of Measure: Percent of Participants
1.7 5.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.140
Comments [Not Specified]
Method Regression, Logistic
Comments If logistic regression sample size requirements are not met, the p-value from Fisher's exact test is used instead.
5.Secondary Outcome
Title Percentage of Participants Achieving ACR20 Response - Placebo Versus Baricitinib 2 mg
Hide Description ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis. 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 using VAS, Patient's Global Assessment of Disease Activity using VAS, HAQ-DI, pain due to arthritis, and hsCRP. Participants with missing responses and participants who discontinue study or drug or are rescued before analysis time point are deemed non-responders.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat (mITT) population includes all randomized participants who received at least 1 dose of the study drug. Participants will be analyzed according to the study drug to which they were randomized. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.
Arm/Group Title Placebo Baricitinib 2 mg
Hide Arm/Group Description:
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 2 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Overall Number of Participants Analyzed 176 174
Measure Type: Number
Unit of Measure: Percentage of Participants
27.3 48.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
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 If logistic regression sample size requirements are not met, the p-value from Fisher's exact test is used instead.
6.Secondary Outcome
Title Change From Baseline in HAQ-DI Score - Placebo Versus Baricitinib 2 mg
Hide Description The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty [0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate the HAQ-DI score. Total scores 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
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mBOCF.
Arm/Group Title Placebo Baricitinib 2 mg
Hide Arm/Group Description:
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 2 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Overall Number of Participants Analyzed 176 174
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
-0.20  (0.50) -0.38  (0.51)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
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 ANCOVA
Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in the DAS28 - hsCRP - Placebo Versus Baricitinib 2 mg
Hide Description DAS28 consisted of composite score of following variables: TJC28, SJC28, hsCRP (mg/mL), and Patient's Global Assessment of Disease Activity. 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. Total scores ranged from 1.0-9.4, where lower scores indicated less disease activity.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mBOCF.
Arm/Group Title Placebo Baricitinib 2 mg
Hide Arm/Group Description:
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 2 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Overall Number of Participants Analyzed 176 174
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
-0.85  (1.19) -1.53  (1.34)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
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 ANCOVA
Comments [Not Specified]
8.Secondary Outcome
Title Percentage of Participants Achieving ACR/EULAR Remission - SDAI ≤3.3 - Placebo Versus Baricitinib 2 mg
Hide Description The ACR/EULAR definitions of rheumatoid arthritis (RA) remission includes an index-based definition. The index-based definition of remission occurs with a SDAI score ≤3.3. The SDAI is a tool for measurement of disease activity in RA that integrates TJC28 (0 to 28), SJC28 (0 to 28), acute phase response using C-reactive protein (0.1 to 10.0 mg/dL), Patient's Global Assessment of Disease Activity using VAS (0 to 10.0 cm), and Physician's Global Assessment of Disease Activity using VAS (0 to 10.0 cm). Lower scores indicated less disease activity.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized or assigned per protocol. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.
Arm/Group Title Placebo Baricitinib 2 mg
Hide Arm/Group Description:
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 2 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Overall Number of Participants Analyzed 176 174
Measure Type: Number
Unit of Measure: Percent of Participants
1.7 2.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.723
Comments [Not Specified]
Method Regression, Logistic
Comments If logistic regression sample size requirements are not met, the p-value from Fisher's exact test is used instead.
9.Secondary Outcome
Title Percentage of Participants Achieving ACR20 Response
Hide Description ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis. 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 using VAS, Patient's Global Assessment of Disease Activity using VAS, HAQ-DI, pain due to arthritis, and hsCRP. Participants with missing responses and participants who discontinue study or drug or are rescued before analysis time point are deemed non-responders.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat (mITT) population includes all randomized participants who received at least 1 dose of the study drug. Participants will be analyzed according to the study drug to which they were randomized. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.
Arm/Group Title Placebo Baricitinib 2 mg Baricitinib 4 mg
Hide Arm/Group Description:
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 2 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Overall Number of Participants Analyzed 176 174 177
Measure Type: Number
Unit of Measure: Percentage of Participants
27.3 44.8 46.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments a priori p-value significance threshold: 2-sided <=0.05
Method Regression, Logistic
Comments If logistic regression sample size requirements are not met, the p-value from Fisher's exact test is used instead.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments a priori p-value significance threshold: 2-sided <=0.05
Method Regression, Logistic
Comments If logistic regression sample size requirements are not met, the p-value from Fisher's exact test is used instead.
10.Secondary Outcome
Title Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response
Hide Description ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in RA. ACR50 Responder is a participant who has at least 50% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, HAQ-DI, pain due to arthritis, and hsCRP. Participants with missing responses and participants who discontinue study or drug or are rescued before analysis time point are deemed non-responders.
Time Frame Week 12 and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.
Arm/Group Title Placebo Baricitinib 2 mg Baricitinib 4 mg
Hide Arm/Group Description:
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 2 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Overall Number of Participants Analyzed 176 174 177
Measure Type: Number
Unit of Measure: Percentage of Participants
Week 12 8.0 20.1 28.2
Week 24 13.1 23.0 29.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments Week 12
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method Regression, Logistic
Comments If logistic regression sample size requirements are not met, the p-value from Fisher's exact test is used instead.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments Week 12
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method Regression, Logistic
Comments If logistic regression sample size requirements are not met, the p-value from Fisher's exact test is used instead.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments Week 24
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method Regression, Logistic
Comments If logistic regression sample size requirements are not met, the p-value from Fisher's exact test is used instead.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments Week 24
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method Regression, Logistic
Comments If logistic regression sample size requirements are not met, the p-value from Fisher's exact test is used instead.
11.Secondary Outcome
Title Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
Hide Description ACR70 Responder Index is a composite of clinical, laboratory, and functional measures in RA. ACR70 Responder is a participant who has at least 70% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, HAQ-DI, pain due to arthritis, and hsCRP. Participants with missing responses and participants who discontinue study or drug or are rescued before analysis time point are deemed non-responders.
Time Frame Week 12 and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.
Arm/Group Title Placebo Baricitinib 2 mg Baricitinib 4 mg
Hide Arm/Group Description:
Placebo administered PO QD through Week 24. Participants will continue to take background cDMARD therapy throughout study.
Baricitinib 2 mg administered PO QD through Week 24. Participants will continue to take background cDMARD therapy throughout study.
Baricitinib 4 mg administered PO QD through Week 24. Participants will continue to take background cDMARD therapy throughout study.
Overall Number of Participants Analyzed 176 174 177
Measure Type: Number
Unit of Measure: Percentage of Participants
Week 12 2.3 12.6 11.3
Week 24 3.4 13.2 16.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments Week 12
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method Regression, Logistic
Comments If logistic regression sample size requirements are not met, the p-value from Fisher's exact test is used instead.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments Week 12
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method Regression, Logistic
Comments If logistic regression sample size requirements are not met, the p-value from Fisher's exact test is used instead.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments Week 24
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method Regression, Logistic
Comments If logistic regression sample size requirements are not met, the p-value from Fisher's exact test is used instead.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments Week 24
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method Regression, Logistic
Comments If logistic regression sample size requirements are not met, the p-value from Fisher's exact test is used instead.
12.Secondary Outcome
Title Change From Baseline in DAS28 - Erythrocyte Sedimentation Rate (ESR)
Hide Description DAS28 consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), ESR (millimeters per hour), and Patient's Global Assessment of Disease Activity. DAS28 was calculated using following formula: DAS28-ESR=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.70*natural log(ESR)+0.014*Patient's Global VAS. Total scores ranged from 1.0-9.4, where lower scores indicated less disease activity.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. 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 2 mg Baricitinib 4 mg
Hide Arm/Group Description:
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
baricitinib 2 mg administered PO QD through Week 24. Participants will continue to take background cDMARD therapy throughout study.
Baricitinib 4 mg administered PO QD through Week 24. Participants will continue to take background cDMARD therapy throughout study.
Overall Number of Participants Analyzed 168 169 173
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
-0.92  (1.21) -1.52  (1.37) -1.80  (1.44)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method ANCOVA
Comments [Not Specified]
13.Secondary Outcome
Title Change From Baseline in Clinical Disease Activity Index Score
Hide Description The CDAI is a tool for measurement of disease activity in RA that does not require a laboratory component and was scored by the investigative site. It integrates TJC28 (scored 0-28 with higher scores indicating higher disease activity), SJC28 (scored 0-28 with higher scores indicating higher disease activity), Patient's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity), and Physician's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity). The CDAI is calculated by summing the values of the 4 components. CDAI scores range from 0 to 76; lower scores indicated lower disease activity. A negative change from baseline indicates improvement in condition.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
Arm/Group Title Placebo Baricitinib 2 mg Baricitinib 4 mg
Hide Arm/Group Description:
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 2 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Overall Number of Participants Analyzed 170 169 171
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
-12.19  (16.96) -17.17  (16.96) -20.30  (16.29)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method ANCOVA
Comments [Not Specified]
14.Secondary Outcome
Title Change From Baseline in Measures of SDAI Score
Hide Description

The 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 visual analog scale (cm), and Physician's Global Assessment of Disease Activity using visual analog scale (cm). The SDAI is calculated by summing the values of the 5 components. Lower scores indicated less disease activity.

The SDAI is expressed as a score on a scale with the minimum score=0 (best) to maximum score=86 (worst). A negative change from baseline indicates an improvement.

Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
Arm/Group Title Placebo Baricitinib 2 mg Baricitinib 4 mg
Hide Arm/Group Description:
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 2 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Overall Number of Participants Analyzed 170 169 171
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
-12.07  (17.50) -17.80  (17.50) -21.26  (17.01)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method ANCOVA
Comments [Not Specified]
15.Secondary Outcome
Title Percentage of Participants Achieving ACR/EULAR Remission – Boolean Remission
Hide 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 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.
Arm/Group Title Placebo Baricitinib 2 mg Baricitinib 4 mg
Hide Arm/Group Description:
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 2 mg administered PO QD through Week 24. Participants will continue to take background cDMARD therapy throughout study.
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Overall Number of Participants Analyzed 176 174 177
Measure Type: Number
Unit of Measure: Percentage of Participants
1.1 4.0 6.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method Regression, Logistic
Comments If logistic regression sample size requirements are not met, the p-value from Fisher's exact test is used instead.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.104
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method Regression, Logistic
Comments If logistic regression sample size requirements are not met, the p-value from Fisher's exact test is used instead.
16.Secondary Outcome
Title Change From Baseline in Duration of Participant Reported Outcome - Morning Joint Stiffness
Hide Description Participants reported the duration of their morning joint stiffness (MJS) in hours and minutes. The participants were asked about their duration of morning joint stiffness on the day prior to the study visit to capture actual symptoms, since the participant may have had an atypical morning routine on that day. If morning joint stiffness duration was longer than 12 hours (720 minutes), it was truncated to 720 minutes for statistical presentations and analyses. A decrease in duration of morning joint stiffness indicated an improvement in the participant's condition.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
Arm/Group Title Placebo Baricitinib 2 mg Baricitinib 4 mg
Hide Arm/Group Description:
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 2 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Overall Number of Participants Analyzed 172 172 175
Median (95% Confidence Interval)
Unit of Measure: Minutes
-8.0
(-15.0 to 0.0)
-25.5
(-40.0 to -15.0)
-27.0
(-40.0 to -15.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
17.Secondary Outcome
Title Change From Baseline in Worst Tiredness Numeric Rating Scale (NRS)
Hide Description A participant-administered, single-item, 11-point horizontal scale anchored at 0 and 10, with 0 representing (no tiredness) and 10 representing (as bad as you can imagine). Participants rate their tiredness by selecting the one number that describes their worst level of tiredness during the past 24 hours. Total scores ranged from 0-10.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
Arm/Group Title Placebo Baricitinib 2 mg Baricitinib 4 mg
Hide Arm/Group Description:
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 2 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Overall Number of Participants Analyzed 172 172 175
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
-1.1  (2.3) -1.8  (2.7) -2.0  (2.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.018
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method ANCOVA
Comments [Not Specified]
18.Secondary Outcome
Title Change From Baseline in Worst Joint Pain NRS
Hide Description Participant-administered, single-item, 11-point horizontal scale anchored at 0 and 10, with 0 representing (no joint pain) and 10 representing (pain as bad as you can imagine). Participants rate their joint pain by selecting the one number that describes their worst level of joint pain during the past 24 hours. Total scores ranged from 0-10.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
Arm/Group Title Placebo Baricitinib 2 mg Baricitinib 4 mg
Hide Arm/Group Description:
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 2 mg administered PO QD through Week 24. Participants will continue to take background cDMARD therapy throughout study.
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Overall Number of Participants Analyzed 172 172 175
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
-1.2  (2.4) -2.1  (2.5) -2.5  (2.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method ANCOVA
Comments [Not Specified]
19.Secondary Outcome
Title Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale Scores
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
Arm/Group Title Placebo Baricitinib 2 mg Baricitinib 4 mg
Hide Arm/Group Description:
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 2 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Overall Number of Participants Analyzed 170 170 174
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Week 12 5.9  (10.5) 8.8  (10.0) 8.5  (9.9)
Week 24 6.6  (10.7) 8.8  (10.4) 9.7  (10.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments Week 12
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments Week 12
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments Week 24
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments Week 24
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.026
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method ANCOVA
Comments [Not Specified]
20.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)
Hide 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.
Time Frame Baseline, Week 12, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using NRI.
Arm/Group Title Placebo Baricitinib 2 mg Baricitinib 4 mg
Hide Arm/Group Description:
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 2 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Overall Number of Participants Analyzed 168 168 174
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Week 12 MCS 1.6  (10.7) 3.4  (9.7) 2.4  (10.0)
Week 24 MCS 2.5  (10.8) 3.2  (11.5) 3.3  (10.6)
Week 12 PCS 3.3  (8.0) 6.3  (8.8) 6.4  (8.8)
Week 24 PCS 2.4  (8.2) 6.4  (8.9) 7.0  (9.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments MCS Week 12
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.448
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments MCS Week 12
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.058
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments MCS Week 24
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.446
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments MCS Week 24
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.401
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments PCS Week 12
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments PCS Week 12
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments PCS Week 24
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments PCS Week 24
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
21.Secondary Outcome
Title Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores
Hide Description European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a standardized measure of health status of the participant. The first component is 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. The second component is a self-perceived health score which is assessed using a VAS that ranged from 0 to 100 millimeter (mm), where 0 mm indicated the worst health you can imagine and 100 mm indicated the best health you can imagine.
Time Frame Baseline, Week 12, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized. Missing values due to discontinuation of study or drug, rescue, or missing data were imputed using mLOCF.
Arm/Group Title Placebo Baricitinib 2 mg Baricitinib 4 mg
Hide Arm/Group Description:
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 2 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Overall Number of Participants Analyzed 168 168 173
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Index Score (US Algorithm) Wk 12 (N=168,168,173) 0.035  (0.167) 0.080  (0.152) 0.128  (0.148)
Index Score (US Algorithm) Wk 24 (N=167,168,173) 0.042  (0.166) 0.082  (0.170) 0.128  (0.157)
Index Score (UK Algorithm) Wk 12 (N=168,168,173) 0.052  (0.250) 0.116  (0.224) 0.191  (0.224)
Index Score (UK Algorithm) Wk 24 (N=167,168,173) 0.064  (0.245) 0.122  (0.250) 0.192  (0.237)
Self-Perceived Health Wk 12 (N=168,168,173) 4.1  (29.0) 14.1  (24.2) 10.3  (27.3)
Self-Perceived Health Wk 24 (N=167,168,173) 3.8  (27.8) 11.4  (26.5) 13.3  (29.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments Week 12, US Algorithm
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments Week 12, US Algorithm
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments Week 24, US Algorithm
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments Week 24, US Algorithm
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments Week 12, UK Algorithm
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments Week 12, UK Algorithm
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments Week 24, UK Algorithm
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments Week 24, UK Algorithm
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments a priori p-value significance threshold: 2-sided ≤0.05
Method ANCOVA
Comments [Not Specified]
22.Secondary Outcome
Title Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores
Hide Description The WPAI-RA participant 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. Using 6 questions, it yields four types of scores: absenteeism (work time missed), presenteeism (impairment at work), work productivity loss (overall work impairment), and activity impairment, with outcomes expressed as impairment percentages. Percentage work time missed absenteeism: Q2/(Q2+Q4)*100, Percentage impairment while working presenteeism: Q5/10*100; Percentage overall work impairment work productivity loss: Q2/(Q2+Q4)+[(1-Q2/(Q2+Q4))x(Q5/10)]*100; Percentage activity impairment activity impairment: Q6/10*100. Higher numbers indicate greater impairment and less productivity, that is, worse outcomes.
Time Frame Baseline, Week 12, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population includes all randomized participants who received at least 1 dose of the study drug. Participants were analyzed according to the study drug to which they were randomized.
Arm/Group Title Placebo Baricitinib 2 mg Baricitinib 4 mg
Hide Arm/Group Description:
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 2 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
Overall Number of Participants Analyzed 176 174 177
Mean (Standard Deviation)
Unit of Measure: Percentage of Impairment
Absenteeism Week 12 3.2  (23.8) -6.7  (26.6) -6.5  (22.1)
Absenteeism Week 24 0.9  (12.4) -1.9  (31.4) -2.3  (29.5)
Presenteeism Week 12 -4.1  (26.4) -12.0  (24.0) -10.5  (24.0)
Presenteeism Week 24 -7.1  (30.5) -11.4  (24.9) -15.6  (25.4)
Work Productivity Loss Week 12 -4.2  (27.8) -13.7  (26.7) -12.3  (24.8)
Work Productivity Loss Week 24 -6.0  (33.4) -13.2  (27.6) -14.8  (32.4)
Activity Impairment Week 12 -10.4  (22.8) -16.0  (25.5) -18.1  (24.8)
Activity Impairment Week 24 -15.7  (25.5) -20.8  (23.7) -25.8  (25.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments Absenteeism Week 12
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.362
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments Absenteeism Week 12
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.170
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments Absenteeism Week 24
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.753
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments Absenteeism Week 24
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.715
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments Presenteeism Week 12
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.077
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments Presenteeism Week 12
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.058
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments Presenteeism Week 24
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.232
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments Presenteeism Week 24
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.534
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments Work Productivity Loss Week 12
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.079
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments Work Productivity Loss Week 12
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.070
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments Work Productivity Loss Week 24
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.327
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments Work Productivity Loss Week 24
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.479
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments Activity Impairment Week 12
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments Activity Impairment Week 12
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 4 mg
Comments Activity Impairment Week 24
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Placebo, Baricitinib 2 mg
Comments Activity Impairment Week 24
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.030
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
23.Secondary Outcome
Title Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of Baricitinib
Hide Description [Not Specified]
Time Frame Week 0 (Baseline): 15 min. post-dose, 1 hour post-dose. Week 4 (Day 28 ±2 days): 2 to 4 hours post-dose. Week 8 (Day 56 ±3 days): 4 to 6 hours post-dose. Week 12 (Day 84 ±3 days): Pre-dose. Week 24 (Day 168 ±5 days): Pre-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug (during study or rescue treatment) with evaluable PK data. Participants who initially received 2 mg with renal impairment were randomized to 4mg (N=11). Participants starting on 4mg (N=177) and participants rescued to 4mg (N=33) are included in the PK baricitinib 4 mg arm.
Arm/Group Title Baricitinib 2 mg Baricitinib 4 mg
Hide Arm/Group Description:

Baricitinib 2 mg administered PO QD through Week 24 (N=185). Participants who were randomized to 4mg (N=11) but actually received 2 mg due to moderate renal impairment were included in the 2-mg group.

Participants continued to take background cDMARD therapy throughout study.

Baricitinib 4 mg administered PO QD through Week 24 (n=177). Participants rescued to 4mg (N=33) are included in the PK baricitinib 4 mg arm.

Participants continued to take background cDMARD therapy throughout study.

Overall Number of Participants Analyzed 185 210
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanomoles/Liter (nmol/L)
65.6
(21.4%)
130
(19.3%)
24.Secondary Outcome
Title Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of Baricitinib
Hide Description [Not Specified]
Time Frame Week 0 (Baseline): 15 min. post-dose, 1 hour post-dose. Week 4 (Day 28 ±2 days): 2 to 4 hours post-dose. Week 8 (Day 56 ±3 days): 4 to 6 hours post-dose. Week 12 (Day 84 ±3 days): Pre-dose. Week 24 (Day 168 ±5 days): Pre-dose.
Hide Outcome Measure Data
Hide 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 2 mg Baricitinib 4 mg
Hide Arm/Group Description:

Baricitinib 2 mg administered PO QD through Week 24 (N=185). Participants who were randomized to 4mg (N=11) but actually received 2 mg due to moderate renal impairment were included in the 2-mg group.

Participants continued to take background cDMARD therapy throughout study.

Baricitinib 4 mg administered PO QD through Week 24 (n=177). Participants rescued to 4mg (N=33) are included in the PK baricitinib 4 mg arm.

Participants continued to take background cDMARD therapy throughout study.

Overall Number of Participants Analyzed 185 210
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanomoles*hour/Liter (nmol*h/L)
615
(43.1%)
1140
(38.7%)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo -Treatment Period Baricitinib 2 mg - Treatment Period Baricitinib 4 mg - Treatment Period Rescue Period Placebo - Follow Up Period Baricitinib 2 mg - Follow Up Period Baricitinib 4 mg - Follow Up Period
Hide Arm/Group Description Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study. Baricitinib 2mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study. Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study. Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study. No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug. No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug. No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug.
All-Cause Mortality
Placebo -Treatment Period Baricitinib 2 mg - Treatment Period Baricitinib 4 mg - Treatment Period Rescue Period Placebo - Follow Up Period Baricitinib 2 mg - Follow Up Period Baricitinib 4 mg - Follow Up Period
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo -Treatment Period Baricitinib 2 mg - Treatment Period Baricitinib 4 mg - Treatment Period Rescue Period Placebo - Follow Up Period Baricitinib 2 mg - Follow Up Period Baricitinib 4 mg - Follow Up Period
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/176 (7.95%)      8/174 (4.60%)      19/177 (10.73%)      2/127 (1.57%)      1/19 (5.26%)      1/9 (11.11%)      0/20 (0.00%)    
Blood and lymphatic system disorders               
Haemorrhagic anaemia  1  1/176 (0.57%)  1 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Iron deficiency anaemia  1  0/176 (0.00%)  0 0/174 (0.00%)  0 1/177 (0.56%)  1 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Leukocytosis  1  1/176 (0.57%)  1 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Thrombocytopenia  1  1/176 (0.57%)  1 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Cardiac disorders               
Coronary artery disease  1  0/176 (0.00%)  0 0/174 (0.00%)  0 2/177 (1.13%)  2 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Myocardial infarction  1  0/176 (0.00%)  0 0/174 (0.00%)  0 1/177 (0.56%)  1 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Tachycardia  1  1/176 (0.57%)  1 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Ear and labyrinth disorders               
Motion sickness  1  0/176 (0.00%)  0 0/174 (0.00%)  0 1/177 (0.56%)  1 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Vertigo positional  1  0/176 (0.00%)  0 0/174 (0.00%)  0 1/177 (0.56%)  1 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Gastrointestinal disorders               
Diverticulum intestinal haemorrhagic  1  0/176 (0.00%)  0 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 1/9 (11.11%)  1 0/20 (0.00%)  0
Inguinal hernia  1  0/176 (0.00%)  0 0/174 (0.00%)  0 1/177 (0.56%)  1 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Oral disorder  1  0/176 (0.00%)  0 1/174 (0.57%)  1 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
General disorders               
Medical device complication  1  0/176 (0.00%)  0 0/174 (0.00%)  0 1/177 (0.56%)  1 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Hepatobiliary disorders               
Cholecystitis  1  0/176 (0.00%)  0 1/174 (0.57%)  1 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Infections and infestations               
Campylobacter gastroenteritis  1  0/176 (0.00%)  0 1/174 (0.57%)  1 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Cellulitis  1  2/176 (1.14%)  2 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 1/19 (5.26%)  1 0/9 (0.00%)  0 0/20 (0.00%)  0
Gastroenteritis  1  0/176 (0.00%)  0 0/174 (0.00%)  0 1/177 (0.56%)  1 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Gastroenteritis viral  1  0/176 (0.00%)  0 0/174 (0.00%)  0 1/177 (0.56%)  1 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Herpes zoster  1  1/176 (0.57%)  1 0/174 (0.00%)  0 1/177 (0.56%)  1 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Intervertebral discitis  1  0/176 (0.00%)  0 1/174 (0.57%)  1 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Osteomyelitis  1  0/176 (0.00%)  0 1/174 (0.57%)  1 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Pneumonia  1  1/176 (0.57%)  1 1/174 (0.57%)  1 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Tooth infection  1  1/176 (0.57%)  1 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Upper respiratory tract infection  1  0/176 (0.00%)  0 1/174 (0.57%)  1 1/177 (0.56%)  1 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Urinary tract infection  1  0/176 (0.00%)  0 0/174 (0.00%)  0 2/177 (1.13%)  2 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Vulval abscess  1  0/145 (0.00%)  0 0/137 (0.00%)  0 1/149 (0.67%)  1 0/113 (0.00%)  0 0/16 (0.00%)  0 0/9 (0.00%)  0 0/18 (0.00%)  0
Injury, poisoning and procedural complications               
Accident at work  1  0/176 (0.00%)  0 0/174 (0.00%)  0 1/177 (0.56%)  1 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Acetabulum fracture  1  1/176 (0.57%)  1 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Alcohol poisoning  1  1/176 (0.57%)  1 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Bone contusion  1  0/176 (0.00%)  0 0/174 (0.00%)  0 1/177 (0.56%)  1 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Cardiac contusion  1  1/176 (0.57%)  1 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Concussion  1  0/176 (0.00%)  0 1/174 (0.57%)  1 1/177 (0.56%)  1 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Facial bones fracture  1  1/176 (0.57%)  1 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Fall  1  0/176 (0.00%)  0 0/174 (0.00%)  0 1/177 (0.56%)  1 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Fractured sacrum  1  1/176 (0.57%)  1 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Hand fracture  1  1/176 (0.57%)  1 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Laceration  1  1/176 (0.57%)  1 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Ligament sprain  1  0/176 (0.00%)  0 1/174 (0.57%)  1 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Lower limb fracture  1  1/176 (0.57%)  1 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Muscle rupture  1  0/176 (0.00%)  0 0/174 (0.00%)  0 0/177 (0.00%)  0 1/127 (0.79%)  1 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Road traffic accident  1  1/176 (0.57%)  1 1/174 (0.57%)  1 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Spinal fracture  1  1/176 (0.57%)  1 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Ulna fracture  1  1/176 (0.57%)  1 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Investigations               
Blood alkaline phosphatase increased  1  0/176 (0.00%)  0 0/174 (0.00%)  0 1/177 (0.56%)  1 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Blood creatine phosphokinase increased  1  1/176 (0.57%)  1 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Hepatic enzyme increased  1  1/176 (0.57%)  1 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Weight decreased  1  0/176 (0.00%)  0 0/174 (0.00%)  0 1/177 (0.56%)  1 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Metabolism and nutrition disorders               
Electrolyte imbalance  1  1/176 (0.57%)  1 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Hyperglycaemia  1  1/176 (0.57%)  1 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Malnutrition  1  1/176 (0.57%)  1 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Musculoskeletal and connective tissue disorders               
Osteoarthritis  1  1/176 (0.57%)  1 1/174 (0.57%)  1 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Rheumatoid arthritis  1  3/176 (1.70%)  3 0/174 (0.00%)  0 2/177 (1.13%)  3 1/127 (0.79%)  1 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Synovitis  1  0/176 (0.00%)  0 0/174 (0.00%)  0 1/177 (0.56%)  1 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Nervous system disorders               
Basilar artery thrombosis  1  0/176 (0.00%)  0 0/174 (0.00%)  0 1/177 (0.56%)  1 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Carpal tunnel syndrome  1  1/176 (0.57%)  1 1/174 (0.57%)  1 0/177 (0.00%)  0 1/127 (0.79%)  1 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Headache  1  0/176 (0.00%)  0 0/174 (0.00%)  0 1/177 (0.56%)  1 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Transient global amnesia  1  0/176 (0.00%)  0 0/174 (0.00%)  0 1/177 (0.56%)  1 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Vertebral artery thrombosis  1  0/176 (0.00%)  0 0/174 (0.00%)  0 1/177 (0.56%)  1 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Psychiatric disorders               
Confusional state  1  1/176 (0.57%)  1 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Delirium  1  1/176 (0.57%)  1 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Renal and urinary disorders               
Renal failure  1  1/176 (0.57%)  1 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Respiratory, thoracic and mediastinal disorders               
Asthma  1  0/176 (0.00%)  0 1/174 (0.57%)  1 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Pleuritic pain  1  0/176 (0.00%)  0 0/174 (0.00%)  0 1/177 (0.56%)  1 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Pneumonia aspiration  1  0/176 (0.00%)  0 1/174 (0.57%)  1 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Pulmonary mass  1  1/176 (0.57%)  1 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Vascular disorders               
Hypertension  1  2/176 (1.14%)  2 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Hypertensive crisis  1  1/176 (0.57%)  1 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Peripheral arterial occlusive disease  1  0/176 (0.00%)  0 1/174 (0.57%)  1 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Peripheral embolism  1  0/176 (0.00%)  0 1/174 (0.57%)  1 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Placebo -Treatment Period Baricitinib 2 mg - Treatment Period Baricitinib 4 mg - Treatment Period Rescue Period Placebo - Follow Up Period Baricitinib 2 mg - Follow Up Period Baricitinib 4 mg - Follow Up Period
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   79/176 (44.89%)      105/174 (60.34%)      102/177 (57.63%)      6/127 (4.72%)      2/19 (10.53%)      4/9 (44.44%)      1/20 (5.00%)    
Blood and lymphatic system disorders               
Anaemia  1  2/176 (1.14%)  2 4/174 (2.30%)  4 1/177 (0.56%)  1 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Lymphopenia  1  0/176 (0.00%)  0 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 1/9 (11.11%)  1 0/20 (0.00%)  0
Eye disorders               
Episcleritis  1  0/176 (0.00%)  0 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 1/19 (5.26%)  1 0/9 (0.00%)  0 0/20 (0.00%)  0
Gastrointestinal disorders               
Abdominal pain  1  4/176 (2.27%)  4 5/174 (2.87%)  5 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Abdominal pain upper  1  1/176 (0.57%)  1 7/174 (4.02%)  7 4/177 (2.26%)  4 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Constipation  1  4/176 (2.27%)  5 4/174 (2.30%)  4 3/177 (1.69%)  3 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Diarrhoea  1  12/176 (6.82%)  12 10/174 (5.75%)  10 7/177 (3.95%)  7 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Gastritis  1  0/176 (0.00%)  0 2/174 (1.15%)  2 4/177 (2.26%)  4 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Gastrooesophageal reflux disease  1  4/176 (2.27%)  4 3/174 (1.72%)  3 2/177 (1.13%)  2 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Nausea  1  5/176 (2.84%)  6 7/174 (4.02%)  9 10/177 (5.65%)  10 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Vomiting  1  2/176 (1.14%)  2 4/174 (2.30%)  5 4/177 (2.26%)  4 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
General disorders               
Fatigue  1  5/176 (2.84%)  5 6/174 (3.45%)  6 3/177 (1.69%)  4 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Pyrexia  1  1/176 (0.57%)  1 7/174 (4.02%)  8 3/177 (1.69%)  3 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Infections and infestations               
Bronchitis  1  6/176 (3.41%)  7 6/174 (3.45%)  7 10/177 (5.65%)  12 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Cellulitis  1  0/176 (0.00%)  0 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 1/9 (11.11%)  1 0/20 (0.00%)  0
Cervicitis  1  0/145 (0.00%)  0 0/137 (0.00%)  0 0/149 (0.00%)  0 0/113 (0.00%)  0 0/16 (0.00%)  0 0/9 (0.00%)  0 1/18 (5.56%)  1
Conjunctivitis  1  0/176 (0.00%)  0 0/174 (0.00%)  0 0/177 (0.00%)  0 0/127 (0.00%)  0 1/19 (5.26%)  1 0/9 (0.00%)  0 0/20 (0.00%)  0
Gastroenteritis  1  3/176 (1.70%)  3 4/174 (2.30%)  4 6/177 (3.39%)  7 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Herpes zoster  1  1/176 (0.57%)  1 2/174 (1.15%)  2 6/177 (3.39%)  6 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Influenza  1  2/176 (1.14%)  2 4/174 (2.30%)  4 8/177 (4.52%)  10 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Nasopharyngitis  1  7/176 (3.98%)  7 12/174 (6.90%)  13 9/177 (5.08%)  10 4/127 (3.15%)  5 1/19 (5.26%)  1 0/9 (0.00%)  0 0/20 (0.00%)  0
Pharyngitis  1  0/176 (0.00%)  0 4/174 (2.30%)  4 5/177 (2.82%)  5 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Rhinitis  1  1/176 (0.57%)  1 5/174 (2.87%)  5 0/177 (0.00%)  0 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Sinusitis  1  1/176 (0.57%)  1 8/174 (4.60%)  8 4/177 (2.26%)  4 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Upper respiratory tract infection  1  8/176 (4.55%)  8 15/174 (8.62%)  17 9/177 (5.08%)  11 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Urinary tract infection  1  6/176 (3.41%)  6 7/174 (4.02%)  10 8/177 (4.52%)  10 0/127 (0.00%)  0 1/19 (5.26%)  1 0/9 (0.00%)  0 0/20 (0.00%)  0
Vulvovaginal candidiasis  1  0/145 (0.00%)  0 3/137 (2.19%)  3 0/149 (0.00%)  0 0/113 (0.00%)  0 0/16 (0.00%)  0 0/9 (0.00%)  0 0/18 (0.00%)  0
Injury, poisoning and procedural complications               
Contusion  1  4/176 (2.27%)  4 4/174 (2.30%)  4 1/177 (0.56%)  1 0/127 (0.00%)  0 0/19 (0.00%)  0 0/9 (0.00%)  0 0/20 (0.00%)  0
Investigations               
Alanine aminotransferase increased  1  1/176 (0.57%)  1 0/174 (0.00%)  0 4/177 (2.26%)  6 0/127 (0.00%)  0