Trial Outcomes & Findings for A Moderate to Severe Rheumatoid Arthritis Study (NCT NCT01721044)
NCT ID: NCT01721044
Last Updated: 2019-09-18
Results Overview
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.
COMPLETED
PHASE3
527 participants
Week 12
2019-09-18
Participant Flow
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.
Participant milestones
| Measure |
Placebo
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 mg
Baricitinib 2 milligram (mg) administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
|---|---|---|---|
|
Treatment Period
STARTED
|
176
|
174
|
177
|
|
Treatment Period
Rescue Week 16-24
|
56
|
38
|
33
|
|
Treatment Period
COMPLETED
|
144
|
157
|
158
|
|
Treatment Period
NOT COMPLETED
|
32
|
17
|
19
|
|
Follow Up
STARTED
|
19
|
9
|
20
|
|
Follow Up
COMPLETED
|
19
|
9
|
20
|
|
Follow Up
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Placebo
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 mg
Baricitinib 2 milligram (mg) administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
|---|---|---|---|
|
Treatment Period
Adverse Event
|
7
|
7
|
10
|
|
Treatment Period
Death
|
0
|
0
|
1
|
|
Treatment Period
Lack of Efficacy
|
16
|
4
|
4
|
|
Treatment Period
Lost to Follow-up
|
0
|
0
|
1
|
|
Treatment Period
Physician Decision
|
1
|
0
|
2
|
|
Treatment Period
Protocol Violation
|
1
|
0
|
0
|
|
Treatment Period
Withdrawal by Subject
|
7
|
6
|
1
|
Baseline Characteristics
Tender joint count based on 68 joints.
Baseline characteristics by cohort
| Measure |
Placebo
n=176 Participants
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 2 mg
n=174 Participants
Baricitinib 2 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=177 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Total
n=527 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
56.0 Years
STANDARD_DEVIATION 10.7 • n=176 Participants
|
55.1 Years
STANDARD_DEVIATION 11.1 • n=174 Participants
|
55.9 Years
STANDARD_DEVIATION 11.3 • n=177 Participants
|
55.7 Years
STANDARD_DEVIATION 11.0 • n=527 Participants
|
|
Sex: Female, Male
Female
|
145 Participants
n=176 Participants
|
137 Participants
n=174 Participants
|
149 Participants
n=177 Participants
|
431 Participants
n=527 Participants
|
|
Sex: Female, Male
Male
|
31 Participants
n=176 Participants
|
37 Participants
n=174 Participants
|
28 Participants
n=177 Participants
|
96 Participants
n=527 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
9 Participants
n=176 Participants
|
12 Participants
n=174 Participants
|
11 Participants
n=177 Participants
|
32 Participants
n=527 Participants
|
|
Race (NIH/OMB)
Asian
|
11 Participants
n=176 Participants
|
9 Participants
n=174 Participants
|
12 Participants
n=177 Participants
|
32 Participants
n=527 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=176 Participants
|
0 Participants
n=174 Participants
|
0 Participants
n=177 Participants
|
0 Participants
n=527 Participants
|
|
Race (NIH/OMB)
Black or African American
|
8 Participants
n=176 Participants
|
9 Participants
n=174 Participants
|
7 Participants
n=177 Participants
|
24 Participants
n=527 Participants
|
|
Race (NIH/OMB)
White
|
147 Participants
n=176 Participants
|
144 Participants
n=174 Participants
|
144 Participants
n=177 Participants
|
435 Participants
n=527 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=176 Participants
|
0 Participants
n=174 Participants
|
0 Participants
n=177 Participants
|
1 Participants
n=527 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=176 Participants
|
0 Participants
n=174 Participants
|
3 Participants
n=177 Participants
|
3 Participants
n=527 Participants
|
|
Region of Enrollment
Argentina
|
9 Participants
n=176 Participants
|
5 Participants
n=174 Participants
|
7 Participants
n=177 Participants
|
21 Participants
n=527 Participants
|
|
Region of Enrollment
Australia
|
8 Participants
n=176 Participants
|
9 Participants
n=174 Participants
|
4 Participants
n=177 Participants
|
21 Participants
n=527 Participants
|
|
Region of Enrollment
Austria
|
5 Participants
n=176 Participants
|
3 Participants
n=174 Participants
|
8 Participants
n=177 Participants
|
16 Participants
n=527 Participants
|
|
Region of Enrollment
Belgium
|
1 Participants
n=176 Participants
|
1 Participants
n=174 Participants
|
1 Participants
n=177 Participants
|
3 Participants
n=527 Participants
|
|
Region of Enrollment
Canada
|
1 Participants
n=176 Participants
|
4 Participants
n=174 Participants
|
3 Participants
n=177 Participants
|
8 Participants
n=527 Participants
|
|
Region of Enrollment
Denmark
|
2 Participants
n=176 Participants
|
3 Participants
n=174 Participants
|
1 Participants
n=177 Participants
|
6 Participants
n=527 Participants
|
|
Region of Enrollment
France
|
7 Participants
n=176 Participants
|
10 Participants
n=174 Participants
|
7 Participants
n=177 Participants
|
24 Participants
n=527 Participants
|
|
Region of Enrollment
Germany
|
8 Participants
n=176 Participants
|
5 Participants
n=174 Participants
|
6 Participants
n=177 Participants
|
19 Participants
n=527 Participants
|
|
Region of Enrollment
Greece
|
4 Participants
n=176 Participants
|
3 Participants
n=174 Participants
|
2 Participants
n=177 Participants
|
9 Participants
n=527 Participants
|
|
Region of Enrollment
Israel
|
9 Participants
n=176 Participants
|
8 Participants
n=174 Participants
|
13 Participants
n=177 Participants
|
30 Participants
n=527 Participants
|
|
Region of Enrollment
Italy
|
2 Participants
n=176 Participants
|
3 Participants
n=174 Participants
|
3 Participants
n=177 Participants
|
8 Participants
n=527 Participants
|
|
Region of Enrollment
Japan
|
6 Participants
n=176 Participants
|
6 Participants
n=174 Participants
|
8 Participants
n=177 Participants
|
20 Participants
n=527 Participants
|
|
Region of Enrollment
Mexico
|
9 Participants
n=176 Participants
|
12 Participants
n=174 Participants
|
10 Participants
n=177 Participants
|
31 Participants
n=527 Participants
|
|
Region of Enrollment
Netherlands
|
0 Participants
n=176 Participants
|
1 Participants
n=174 Participants
|
1 Participants
n=177 Participants
|
2 Participants
n=527 Participants
|
|
Region of Enrollment
Poland
|
10 Participants
n=176 Participants
|
13 Participants
n=174 Participants
|
9 Participants
n=177 Participants
|
32 Participants
n=527 Participants
|
|
Region of Enrollment
South Korea
|
4 Participants
n=176 Participants
|
3 Participants
n=174 Participants
|
3 Participants
n=177 Participants
|
10 Participants
n=527 Participants
|
|
Region of Enrollment
Spain
|
10 Participants
n=176 Participants
|
7 Participants
n=174 Participants
|
10 Participants
n=177 Participants
|
27 Participants
n=527 Participants
|
|
Region of Enrollment
Switzerland
|
1 Participants
n=176 Participants
|
2 Participants
n=174 Participants
|
4 Participants
n=177 Participants
|
7 Participants
n=527 Participants
|
|
Region of Enrollment
Turkey
|
1 Participants
n=176 Participants
|
1 Participants
n=174 Participants
|
1 Participants
n=177 Participants
|
3 Participants
n=527 Participants
|
|
Region of Enrollment
United Kingdom
|
2 Participants
n=176 Participants
|
1 Participants
n=174 Participants
|
1 Participants
n=177 Participants
|
4 Participants
n=527 Participants
|
|
Region of Enrollment
United States
|
77 Participants
n=176 Participants
|
74 Participants
n=174 Participants
|
75 Participants
n=177 Participants
|
226 Participants
n=527 Participants
|
|
Duration of Rheumatoid Arthritis
|
14.0 Years
STANDARD_DEVIATION 9.6 • n=176 Participants
|
13.7 Years
STANDARD_DEVIATION 8.0 • n=174 Participants
|
14.3 Years
STANDARD_DEVIATION 9.4 • n=177 Participants
|
14.0 Years
STANDARD_DEVIATION 9.0 • n=527 Participants
|
|
Tender Joint Count of 68 Evaluable Joints
|
28.3 Number of Joints
STANDARD_DEVIATION 16.4 • n=174 Participants • Tender joint count based on 68 joints.
|
31.0 Number of Joints
STANDARD_DEVIATION 16.3 • n=174 Participants • Tender joint count based on 68 joints.
|
28.1 Number of Joints
STANDARD_DEVIATION 15.6 • n=177 Participants • Tender joint count based on 68 joints.
|
29.1 Number of Joints
STANDARD_DEVIATION 16.1 • n=525 Participants • Tender joint count based on 68 joints.
|
|
Swollen Joint Count of 66 Evaluable Joints
|
17.2 Number of Joints
STANDARD_DEVIATION 10.8 • n=174 Participants • Swollen joint count based on 66 joints.
|
18.6 Number of Joints
STANDARD_DEVIATION 12.3 • n=174 Participants • Swollen joint count based on 66 joints.
|
16.3 Number of Joints
STANDARD_DEVIATION 8.9 • n=177 Participants • Swollen joint count based on 66 joints.
|
17.4 Number of Joints
STANDARD_DEVIATION 10.8 • n=525 Participants • Swollen joint count based on 66 joints.
|
|
High Sensitivity C-Reactive Protein (hsCRP)
|
20.64 milligrams/liter (mg/L)
STANDARD_DEVIATION 25.26 • n=176 Participants
|
19.87 milligrams/liter (mg/L)
STANDARD_DEVIATION 22.48 • n=174 Participants
|
19.76 milligrams/liter (mg/L)
STANDARD_DEVIATION 24.84 • n=177 Participants
|
20.09 milligrams/liter (mg/L)
STANDARD_DEVIATION 24.19 • n=527 Participants
|
PRIMARY outcome
Timeframe: Week 12Population: 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).
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.
Outcome measures
| Measure |
Placebo
n=176 Participants
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=177 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
|---|---|---|---|
|
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response - Placebo Versus Baricitinib 4 mg
|
27.3 Percentage of Participants
|
55.4 Percentage of Participants
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: 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).
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.
Outcome measures
| Measure |
Placebo
n=176 Participants
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=177 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
|---|---|---|---|
|
Change From Baseline in HAQ-DI Score - Placebo Versus Baricitinib 4 mg
|
-0.20 Units on a Scale
Standard Deviation 0.50
|
-0.42 Units on a Scale
Standard Deviation 0.49
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=174 Participants
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=177 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
|---|---|---|---|
|
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
|
-0.85 Units on a Scale
Standard Deviation 1.19
|
-1.81 Units on a Scale
Standard Deviation 1.43
|
—
|
SECONDARY outcome
Timeframe: Week 12Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=176 Participants
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=177 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
|---|---|---|---|
|
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
|
1.7 Percent of Participants
|
5.1 Percent of Participants
|
—
|
SECONDARY outcome
Timeframe: Week 12Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=176 Participants
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=174 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
|---|---|---|---|
|
Percentage of Participants Achieving ACR20 Response - Placebo Versus Baricitinib 2 mg
|
27.3 Percentage of Participants
|
48.9 Percentage of Participants
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=176 Participants
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=174 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
|---|---|---|---|
|
Change From Baseline in HAQ-DI Score - Placebo Versus Baricitinib 2 mg
|
-0.20 Units on a Scale
Standard Deviation 0.50
|
-0.38 Units on a Scale
Standard Deviation 0.51
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=176 Participants
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=174 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
|---|---|---|---|
|
Change From Baseline in the DAS28 - hsCRP - Placebo Versus Baricitinib 2 mg
|
-0.85 Units on a Scale
Standard Deviation 1.19
|
-1.53 Units on a Scale
Standard Deviation 1.34
|
—
|
SECONDARY outcome
Timeframe: Week 12Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=176 Participants
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=174 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
|---|---|---|---|
|
Percentage of Participants Achieving ACR/EULAR Remission - SDAI ≤3.3 - Placebo Versus Baricitinib 2 mg
|
1.7 Percent of Participants
|
2.3 Percent of Participants
|
—
|
SECONDARY outcome
Timeframe: Week 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=176 Participants
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=174 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=177 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
|---|---|---|---|
|
Percentage of Participants Achieving ACR20 Response
|
27.3 Percentage of Participants
|
44.8 Percentage of Participants
|
46.3 Percentage of Participants
|
SECONDARY outcome
Timeframe: Week 12 and Week 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=176 Participants
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=174 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=177 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
|---|---|---|---|
|
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response
Week 12
|
8.0 Percentage of Participants
|
20.1 Percentage of Participants
|
28.2 Percentage of Participants
|
|
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response
Week 24
|
13.1 Percentage of Participants
|
23.0 Percentage of Participants
|
29.4 Percentage of Participants
|
SECONDARY outcome
Timeframe: Week 12 and Week 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=176 Participants
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=174 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=177 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
|---|---|---|---|
|
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
Week 12
|
2.3 Percentage of Participants
|
12.6 Percentage of Participants
|
11.3 Percentage of Participants
|
|
Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
Week 24
|
3.4 Percentage of Participants
|
13.2 Percentage of Participants
|
16.9 Percentage of Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: 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).
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.
Outcome measures
| Measure |
Placebo
n=168 Participants
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=169 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=173 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
|---|---|---|---|
|
Change From Baseline in DAS28 - Erythrocyte Sedimentation Rate (ESR)
|
-0.92 Units on a Scale
Standard Deviation 1.21
|
-1.52 Units on a Scale
Standard Deviation 1.37
|
-1.80 Units on a Scale
Standard Deviation 1.44
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=170 Participants
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=169 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=171 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
|---|---|---|---|
|
Change From Baseline in Clinical Disease Activity Index Score
|
-12.19 Units on a Scale
Standard Deviation 16.96
|
-17.17 Units on a Scale
Standard Deviation 16.96
|
-20.30 Units on a Scale
Standard Deviation 16.29
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=170 Participants
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=169 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=171 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
|---|---|---|---|
|
Change From Baseline in Measures of SDAI Score
|
-12.07 Units on a Scale
Standard Deviation 17.50
|
-17.80 Units on a Scale
Standard Deviation 17.50
|
-21.26 Units on a Scale
Standard Deviation 17.01
|
SECONDARY outcome
Timeframe: Week 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=176 Participants
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=174 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=177 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
|---|---|---|---|
|
Percentage of Participants Achieving ACR/EULAR Remission - Boolean Remission
|
1.1 Percentage of Participants
|
4.0 Percentage of Participants
|
6.8 Percentage of Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=172 Participants
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=172 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=175 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
|---|---|---|---|
|
Change From Baseline in Duration of Participant Reported Outcome - Morning Joint Stiffness
|
-8.0 Minutes
Interval -15.0 to 0.0
|
-25.5 Minutes
Interval -40.0 to -15.0
|
-27.0 Minutes
Interval -40.0 to -15.0
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=172 Participants
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=172 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=175 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
|---|---|---|---|
|
Change From Baseline in Worst Tiredness Numeric Rating Scale (NRS)
|
-1.1 Units on a Scale
Standard Deviation 2.3
|
-1.8 Units on a Scale
Standard Deviation 2.7
|
-2.0 Units on a Scale
Standard Deviation 2.6
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=172 Participants
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=172 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=175 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
|---|---|---|---|
|
Change From Baseline in Worst Joint Pain NRS
|
-1.2 Units on a Scale
Standard Deviation 2.4
|
-2.1 Units on a Scale
Standard Deviation 2.5
|
-2.5 Units on a Scale
Standard Deviation 2.7
|
SECONDARY outcome
Timeframe: Baseline, Week 12, Week 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=170 Participants
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=170 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=174 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
|---|---|---|---|
|
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale Scores
Week 24
|
6.6 Units on a Scale
Standard Deviation 10.7
|
8.8 Units on a Scale
Standard Deviation 10.4
|
9.7 Units on a Scale
Standard Deviation 10.7
|
|
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale Scores
Week 12
|
5.9 Units on a Scale
Standard Deviation 10.5
|
8.8 Units on a Scale
Standard Deviation 10.0
|
8.5 Units on a Scale
Standard Deviation 9.9
|
SECONDARY outcome
Timeframe: Baseline, Week 12, Week 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=168 Participants
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=168 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=174 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
|---|---|---|---|
|
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)
Week 12 MCS
|
1.6 Units on a Scale
Standard Deviation 10.7
|
3.4 Units on a Scale
Standard Deviation 9.7
|
2.4 Units on a Scale
Standard Deviation 10.0
|
|
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)
Week 24 MCS
|
2.5 Units on a Scale
Standard Deviation 10.8
|
3.2 Units on a Scale
Standard Deviation 11.5
|
3.3 Units on a Scale
Standard Deviation 10.6
|
|
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)
Week 12 PCS
|
3.3 Units on a Scale
Standard Deviation 8.0
|
6.3 Units on a Scale
Standard Deviation 8.8
|
6.4 Units on a Scale
Standard Deviation 8.8
|
|
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)
Week 24 PCS
|
2.4 Units on a Scale
Standard Deviation 8.2
|
6.4 Units on a Scale
Standard Deviation 8.9
|
7.0 Units on a Scale
Standard Deviation 9.3
|
SECONDARY outcome
Timeframe: Baseline, Week 12, Week 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=168 Participants
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=168 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=173 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
|---|---|---|---|
|
Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores
Index Score (US Algorithm) Wk 24 (N=167,168,173)
|
0.042 Units on a Scale
Standard Deviation 0.166
|
0.082 Units on a Scale
Standard Deviation 0.170
|
0.128 Units on a Scale
Standard Deviation 0.157
|
|
Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores
Index Score (US Algorithm) Wk 12 (N=168,168,173)
|
0.035 Units on a Scale
Standard Deviation 0.167
|
0.080 Units on a Scale
Standard Deviation 0.152
|
0.128 Units on a Scale
Standard Deviation 0.148
|
|
Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores
Index Score (UK Algorithm) Wk 12 (N=168,168,173)
|
0.052 Units on a Scale
Standard Deviation 0.250
|
0.116 Units on a Scale
Standard Deviation 0.224
|
0.191 Units on a Scale
Standard Deviation 0.224
|
|
Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores
Index Score (UK Algorithm) Wk 24 (N=167,168,173)
|
0.064 Units on a Scale
Standard Deviation 0.245
|
0.122 Units on a Scale
Standard Deviation 0.250
|
0.192 Units on a Scale
Standard Deviation 0.237
|
|
Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores
Self-Perceived Health Wk 12 (N=168,168,173)
|
4.1 Units on a Scale
Standard Deviation 29.0
|
14.1 Units on a Scale
Standard Deviation 24.2
|
10.3 Units on a Scale
Standard Deviation 27.3
|
|
Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores
Self-Perceived Health Wk 24 (N=167,168,173)
|
3.8 Units on a Scale
Standard Deviation 27.8
|
11.4 Units on a Scale
Standard Deviation 26.5
|
13.3 Units on a Scale
Standard Deviation 29.0
|
SECONDARY outcome
Timeframe: Baseline, Week 12, Week 24Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=176 Participants
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=174 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=177 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
|---|---|---|---|
|
Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores
Absenteeism Week 12
|
3.2 Percentage of Impairment
Standard Deviation 23.8
|
-6.7 Percentage of Impairment
Standard Deviation 26.6
|
-6.5 Percentage of Impairment
Standard Deviation 22.1
|
|
Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores
Absenteeism Week 24
|
0.9 Percentage of Impairment
Standard Deviation 12.4
|
-1.9 Percentage of Impairment
Standard Deviation 31.4
|
-2.3 Percentage of Impairment
Standard Deviation 29.5
|
|
Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores
Presenteeism Week 12
|
-4.1 Percentage of Impairment
Standard Deviation 26.4
|
-12.0 Percentage of Impairment
Standard Deviation 24.0
|
-10.5 Percentage of Impairment
Standard Deviation 24.0
|
|
Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores
Presenteeism Week 24
|
-7.1 Percentage of Impairment
Standard Deviation 30.5
|
-11.4 Percentage of Impairment
Standard Deviation 24.9
|
-15.6 Percentage of Impairment
Standard Deviation 25.4
|
|
Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores
Work Productivity Loss Week 12
|
-4.2 Percentage of Impairment
Standard Deviation 27.8
|
-13.7 Percentage of Impairment
Standard Deviation 26.7
|
-12.3 Percentage of Impairment
Standard Deviation 24.8
|
|
Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores
Work Productivity Loss Week 24
|
-6.0 Percentage of Impairment
Standard Deviation 33.4
|
-13.2 Percentage of Impairment
Standard Deviation 27.6
|
-14.8 Percentage of Impairment
Standard Deviation 32.4
|
|
Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores
Activity Impairment Week 12
|
-10.4 Percentage of Impairment
Standard Deviation 22.8
|
-16.0 Percentage of Impairment
Standard Deviation 25.5
|
-18.1 Percentage of Impairment
Standard Deviation 24.8
|
|
Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores
Activity Impairment Week 24
|
-15.7 Percentage of Impairment
Standard Deviation 25.5
|
-20.8 Percentage of Impairment
Standard Deviation 23.7
|
-25.8 Percentage of Impairment
Standard Deviation 25.2
|
SECONDARY outcome
Timeframe: 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.Population: 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.
Outcome measures
| Measure |
Placebo
n=185 Participants
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=210 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
|---|---|---|---|
|
Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of Baricitinib
|
65.6 nanomoles/Liter (nmol/L)
Geometric Coefficient of Variation 21.4
|
130 nanomoles/Liter (nmol/L)
Geometric Coefficient of Variation 19.3
|
—
|
SECONDARY outcome
Timeframe: 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.Population: All randomized participants who received at least 1 dose of study drug (during study or rescue treatment) with evaluable PK data.
Outcome measures
| Measure |
Placebo
n=185 Participants
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
n=210 Participants
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
|---|---|---|---|
|
Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of Baricitinib
|
615 nanomoles*hour/Liter (nmol*h/L)
Geometric Coefficient of Variation 43.1
|
1140 nanomoles*hour/Liter (nmol*h/L)
Geometric Coefficient of Variation 38.7
|
—
|
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
Serious adverse events
| Measure |
Placebo -Treatment Period
n=176 participants at risk
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 2 mg - Treatment Period
n=174 participants at risk
Baricitinib 2mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg - Treatment Period
n=177 participants at risk
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Rescue Period
n=127 participants at risk
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Placebo - Follow Up Period
n=19 participants at risk
No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug.
|
Baricitinib 2 mg - Follow Up Period
n=9 participants at risk
No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug.
|
Baricitinib 4 mg - Follow Up Period
n=20 participants at risk
No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug.
|
|---|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Haemorrhagic anaemia
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
0.00%
0/176
|
0.00%
0/174
|
0.56%
1/177 • Number of events 1
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/176
|
0.00%
0/174
|
1.1%
2/177 • Number of events 2
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/176
|
0.00%
0/174
|
0.56%
1/177 • Number of events 1
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Cardiac disorders
Tachycardia
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Ear and labyrinth disorders
Motion sickness
|
0.00%
0/176
|
0.00%
0/174
|
0.56%
1/177 • Number of events 1
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Ear and labyrinth disorders
Vertigo positional
|
0.00%
0/176
|
0.00%
0/174
|
0.56%
1/177 • Number of events 1
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Gastrointestinal disorders
Diverticulum intestinal haemorrhagic
|
0.00%
0/176
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
11.1%
1/9 • Number of events 1
|
0.00%
0/20
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.00%
0/176
|
0.00%
0/174
|
0.56%
1/177 • Number of events 1
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Gastrointestinal disorders
Oral disorder
|
0.00%
0/176
|
0.57%
1/174 • Number of events 1
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
General disorders
Medical device complication
|
0.00%
0/176
|
0.00%
0/174
|
0.56%
1/177 • Number of events 1
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/176
|
0.57%
1/174 • Number of events 1
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Infections and infestations
Campylobacter gastroenteritis
|
0.00%
0/176
|
0.57%
1/174 • Number of events 1
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Infections and infestations
Cellulitis
|
1.1%
2/176 • Number of events 2
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
5.3%
1/19 • Number of events 1
|
0.00%
0/9
|
0.00%
0/20
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/176
|
0.00%
0/174
|
0.56%
1/177 • Number of events 1
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/176
|
0.00%
0/174
|
0.56%
1/177 • Number of events 1
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Infections and infestations
Herpes zoster
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
0.56%
1/177 • Number of events 1
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Infections and infestations
Intervertebral discitis
|
0.00%
0/176
|
0.57%
1/174 • Number of events 1
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/176
|
0.57%
1/174 • Number of events 1
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Infections and infestations
Pneumonia
|
0.57%
1/176 • Number of events 1
|
0.57%
1/174 • Number of events 1
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Infections and infestations
Tooth infection
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/176
|
0.57%
1/174 • Number of events 1
|
0.56%
1/177 • Number of events 1
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/176
|
0.00%
0/174
|
1.1%
2/177 • Number of events 2
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Infections and infestations
Vulval abscess
|
0.00%
0/145
|
0.00%
0/137
|
0.67%
1/149 • Number of events 1
|
0.00%
0/113
|
0.00%
0/16
|
0.00%
0/9
|
0.00%
0/18
|
|
Injury, poisoning and procedural complications
Accident at work
|
0.00%
0/176
|
0.00%
0/174
|
0.56%
1/177 • Number of events 1
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Injury, poisoning and procedural complications
Acetabulum fracture
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Injury, poisoning and procedural complications
Alcohol poisoning
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Injury, poisoning and procedural complications
Bone contusion
|
0.00%
0/176
|
0.00%
0/174
|
0.56%
1/177 • Number of events 1
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Injury, poisoning and procedural complications
Cardiac contusion
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Injury, poisoning and procedural complications
Concussion
|
0.00%
0/176
|
0.57%
1/174 • Number of events 1
|
0.56%
1/177 • Number of events 1
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Injury, poisoning and procedural complications
Facial bones fracture
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/176
|
0.00%
0/174
|
0.56%
1/177 • Number of events 1
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Injury, poisoning and procedural complications
Fractured sacrum
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Injury, poisoning and procedural complications
Hand fracture
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Injury, poisoning and procedural complications
Laceration
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
0.00%
0/176
|
0.57%
1/174 • Number of events 1
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Injury, poisoning and procedural complications
Muscle rupture
|
0.00%
0/176
|
0.00%
0/174
|
0.00%
0/177
|
0.79%
1/127 • Number of events 1
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.57%
1/176 • Number of events 1
|
0.57%
1/174 • Number of events 1
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Injury, poisoning and procedural complications
Ulna fracture
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/176
|
0.00%
0/174
|
0.56%
1/177 • Number of events 1
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Investigations
Blood creatine phosphokinase increased
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Investigations
Hepatic enzyme increased
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Investigations
Weight decreased
|
0.00%
0/176
|
0.00%
0/174
|
0.56%
1/177 • Number of events 1
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Metabolism and nutrition disorders
Electrolyte imbalance
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Metabolism and nutrition disorders
Malnutrition
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.57%
1/176 • Number of events 1
|
0.57%
1/174 • Number of events 1
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
1.7%
3/176 • Number of events 3
|
0.00%
0/174
|
1.1%
2/177 • Number of events 3
|
0.79%
1/127 • Number of events 1
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Musculoskeletal and connective tissue disorders
Synovitis
|
0.00%
0/176
|
0.00%
0/174
|
0.56%
1/177 • Number of events 1
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Nervous system disorders
Basilar artery thrombosis
|
0.00%
0/176
|
0.00%
0/174
|
0.56%
1/177 • Number of events 1
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Nervous system disorders
Carpal tunnel syndrome
|
0.57%
1/176 • Number of events 1
|
0.57%
1/174 • Number of events 1
|
0.00%
0/177
|
0.79%
1/127 • Number of events 1
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Nervous system disorders
Headache
|
0.00%
0/176
|
0.00%
0/174
|
0.56%
1/177 • Number of events 1
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Nervous system disorders
Transient global amnesia
|
0.00%
0/176
|
0.00%
0/174
|
0.56%
1/177 • Number of events 1
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Nervous system disorders
Vertebral artery thrombosis
|
0.00%
0/176
|
0.00%
0/174
|
0.56%
1/177 • Number of events 1
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Psychiatric disorders
Confusional state
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Psychiatric disorders
Delirium
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Renal and urinary disorders
Renal failure
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/176
|
0.57%
1/174 • Number of events 1
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
0.00%
0/176
|
0.00%
0/174
|
0.56%
1/177 • Number of events 1
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.00%
0/176
|
0.57%
1/174 • Number of events 1
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary mass
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Vascular disorders
Hypertension
|
1.1%
2/176 • Number of events 2
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Vascular disorders
Hypertensive crisis
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Vascular disorders
Peripheral arterial occlusive disease
|
0.00%
0/176
|
0.57%
1/174 • Number of events 1
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Vascular disorders
Peripheral embolism
|
0.00%
0/176
|
0.57%
1/174 • Number of events 1
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
Other adverse events
| Measure |
Placebo -Treatment Period
n=176 participants at risk
Placebo administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 2 mg - Treatment Period
n=174 participants at risk
Baricitinib 2mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Baricitinib 4 mg - Treatment Period
n=177 participants at risk
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Rescue Period
n=127 participants at risk
Baricitinib 4 mg administered PO QD through Week 24. Participants continued to take background cDMARD therapy throughout study.
|
Placebo - Follow Up Period
n=19 participants at risk
No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug.
|
Baricitinib 2 mg - Follow Up Period
n=9 participants at risk
No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug.
|
Baricitinib 4 mg - Follow Up Period
n=20 participants at risk
No study drug received. Participants return for safety follow-up visit 28 days after the last dose of study drug.
|
|---|---|---|---|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
4.5%
8/176 • Number of events 10
|
1.7%
3/174 • Number of events 4
|
2.8%
5/177 • Number of events 6
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.4%
6/176 • Number of events 6
|
4.6%
8/174 • Number of events 8
|
3.4%
6/177 • Number of events 6
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Blood and lymphatic system disorders
Anaemia
|
1.1%
2/176 • Number of events 2
|
2.3%
4/174 • Number of events 4
|
0.56%
1/177 • Number of events 1
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/176
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
11.1%
1/9 • Number of events 1
|
0.00%
0/20
|
|
Eye disorders
Episcleritis
|
0.00%
0/176
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
5.3%
1/19 • Number of events 1
|
0.00%
0/9
|
0.00%
0/20
|
|
Gastrointestinal disorders
Abdominal pain
|
2.3%
4/176 • Number of events 4
|
2.9%
5/174 • Number of events 5
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.57%
1/176 • Number of events 1
|
4.0%
7/174 • Number of events 7
|
2.3%
4/177 • Number of events 4
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Gastrointestinal disorders
Constipation
|
2.3%
4/176 • Number of events 5
|
2.3%
4/174 • Number of events 4
|
1.7%
3/177 • Number of events 3
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Gastrointestinal disorders
Diarrhoea
|
6.8%
12/176 • Number of events 12
|
5.7%
10/174 • Number of events 10
|
4.0%
7/177 • Number of events 7
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/176
|
1.1%
2/174 • Number of events 2
|
2.3%
4/177 • Number of events 4
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
2.3%
4/176 • Number of events 4
|
1.7%
3/174 • Number of events 3
|
1.1%
2/177 • Number of events 2
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Gastrointestinal disorders
Nausea
|
2.8%
5/176 • Number of events 6
|
4.0%
7/174 • Number of events 9
|
5.6%
10/177 • Number of events 10
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Gastrointestinal disorders
Vomiting
|
1.1%
2/176 • Number of events 2
|
2.3%
4/174 • Number of events 5
|
2.3%
4/177 • Number of events 4
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
General disorders
Fatigue
|
2.8%
5/176 • Number of events 5
|
3.4%
6/174 • Number of events 6
|
1.7%
3/177 • Number of events 4
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
General disorders
Pyrexia
|
0.57%
1/176 • Number of events 1
|
4.0%
7/174 • Number of events 8
|
1.7%
3/177 • Number of events 3
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Infections and infestations
Bronchitis
|
3.4%
6/176 • Number of events 7
|
3.4%
6/174 • Number of events 7
|
5.6%
10/177 • Number of events 12
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Infections and infestations
Cellulitis
|
0.00%
0/176
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
11.1%
1/9 • Number of events 1
|
0.00%
0/20
|
|
Infections and infestations
Cervicitis
|
0.00%
0/145
|
0.00%
0/137
|
0.00%
0/149
|
0.00%
0/113
|
0.00%
0/16
|
0.00%
0/9
|
5.6%
1/18 • Number of events 1
|
|
Infections and infestations
Conjunctivitis
|
0.00%
0/176
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
5.3%
1/19 • Number of events 1
|
0.00%
0/9
|
0.00%
0/20
|
|
Infections and infestations
Gastroenteritis
|
1.7%
3/176 • Number of events 3
|
2.3%
4/174 • Number of events 4
|
3.4%
6/177 • Number of events 7
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Infections and infestations
Herpes zoster
|
0.57%
1/176 • Number of events 1
|
1.1%
2/174 • Number of events 2
|
3.4%
6/177 • Number of events 6
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Infections and infestations
Influenza
|
1.1%
2/176 • Number of events 2
|
2.3%
4/174 • Number of events 4
|
4.5%
8/177 • Number of events 10
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Infections and infestations
Nasopharyngitis
|
4.0%
7/176 • Number of events 7
|
6.9%
12/174 • Number of events 13
|
5.1%
9/177 • Number of events 10
|
3.1%
4/127 • Number of events 5
|
5.3%
1/19 • Number of events 1
|
0.00%
0/9
|
0.00%
0/20
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/176
|
2.3%
4/174 • Number of events 4
|
2.8%
5/177 • Number of events 5
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Infections and infestations
Rhinitis
|
0.57%
1/176 • Number of events 1
|
2.9%
5/174 • Number of events 5
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Infections and infestations
Sinusitis
|
0.57%
1/176 • Number of events 1
|
4.6%
8/174 • Number of events 8
|
2.3%
4/177 • Number of events 4
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Infections and infestations
Upper respiratory tract infection
|
4.5%
8/176 • Number of events 8
|
8.6%
15/174 • Number of events 17
|
5.1%
9/177 • Number of events 11
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Infections and infestations
Urinary tract infection
|
3.4%
6/176 • Number of events 6
|
4.0%
7/174 • Number of events 10
|
4.5%
8/177 • Number of events 10
|
0.00%
0/127
|
5.3%
1/19 • Number of events 1
|
0.00%
0/9
|
0.00%
0/20
|
|
Infections and infestations
Vulvovaginal candidiasis
|
0.00%
0/145
|
2.2%
3/137 • Number of events 3
|
0.00%
0/149
|
0.00%
0/113
|
0.00%
0/16
|
0.00%
0/9
|
0.00%
0/18
|
|
Injury, poisoning and procedural complications
Contusion
|
2.3%
4/176 • Number of events 4
|
2.3%
4/174 • Number of events 4
|
0.56%
1/177 • Number of events 1
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Investigations
Alanine aminotransferase increased
|
0.57%
1/176 • Number of events 1
|
0.00%
0/174
|
2.3%
4/177 • Number of events 6
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/176
|
0.00%
0/174
|
2.8%
5/177 • Number of events 7
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/176
|
2.3%
4/174 • Number of events 4
|
3.4%
6/177 • Number of events 8
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Investigations
Weight increased
|
0.57%
1/176 • Number of events 1
|
2.3%
4/174 • Number of events 4
|
1.7%
3/177 • Number of events 3
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
1.1%
2/176 • Number of events 2
|
0.57%
1/174 • Number of events 1
|
4.0%
7/177 • Number of events 7
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
0.57%
1/176 • Number of events 1
|
1.7%
3/174 • Number of events 3
|
2.8%
5/177 • Number of events 5
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
1.1%
2/176 • Number of events 2
|
1.7%
3/174 • Number of events 3
|
2.3%
4/177 • Number of events 4
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.57%
1/176 • Number of events 1
|
2.9%
5/174 • Number of events 6
|
2.3%
4/177 • Number of events 4
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
2.3%
4/176 • Number of events 4
|
1.1%
2/174 • Number of events 2
|
0.56%
1/177 • Number of events 1
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/176
|
2.3%
4/174 • Number of events 6
|
0.56%
1/177 • Number of events 2
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
4.0%
7/176 • Number of events 8
|
2.9%
5/174 • Number of events 6
|
4.5%
8/177 • Number of events 10
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Nervous system disorders
Headache
|
6.2%
11/176 • Number of events 12
|
9.8%
17/174 • Number of events 17
|
6.8%
12/177 • Number of events 12
|
2.4%
3/127 • Number of events 3
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/176
|
0.00%
0/174
|
0.00%
0/177
|
0.00%
0/127
|
0.00%
0/19
|
11.1%
1/9 • Number of events 1
|
0.00%
0/20
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.4%
6/176 • Number of events 6
|
1.1%
2/174 • Number of events 2
|
2.8%
5/177 • Number of events 5
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
1.1%
2/176 • Number of events 2
|
2.9%
5/174 • Number of events 6
|
2.8%
5/177 • Number of events 5
|
0.00%
0/127
|
0.00%
0/19
|
11.1%
1/9 • Number of events 1
|
0.00%
0/20
|
|
Skin and subcutaneous tissue disorders
Rash
|
1.1%
2/176 • Number of events 2
|
2.9%
5/174 • Number of events 5
|
1.1%
2/177 • Number of events 2
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
|
Vascular disorders
Hypertension
|
2.3%
4/176 • Number of events 4
|
4.0%
7/174 • Number of events 7
|
5.1%
9/177 • Number of events 9
|
0.00%
0/127
|
0.00%
0/19
|
0.00%
0/9
|
0.00%
0/20
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60