Trial Outcomes & Findings for A Study of Baricitinib in Participants With Systemic Lupus Erythematosus (SLE-BRAVE II) (NCT NCT03616964)

Last Updated: 2022-11-23

Results Overview

SRI-4 response defined as 1)greater than or equal to (\>=) 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score 2)no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score and 3)no worsening in Physician Global Assessment (PGA) of Disease Activity (worsening defined as an increase of \>=0.3 from baseline on a 0-3 visual analogue scale). SLEDAI-2K assessment consists of 24 items with total score of 0(no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms,or laboratory parameters related to Systemic Lupus Erythematosus (SLE),divided into 9 organ systems. For each organ system A=severe disease,B=moderate disease,C=mild stable disease,D=inactive,but previously active,E=inactive and never affected. PGA assess disease activity on a visual analogue scale from 0 to 3 (1=mild, 2=moderate, 3=severe).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

778 participants

Primary outcome timeframe

Week 52

Results posted on

2022-11-23

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Participants received 2 placebo tablets: one placebo tablet matching 4 milligram (mg) baricitinib and one placebo tablet matching 2 mg baricitinib administered orally once daily (QD) for 52 weeks.	2 mg Baricitinib Participants received one 2 mg baricitinib tablet and one placebo tablet matching 4 mg baricitinib administered QD for 52 weeks.	4 mg Baricitinib Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.
Overall Study STARTED	257	262	259
Overall Study Received at Least One Dose of Study Drug	256	261	258
Overall Study Safety Population	256	261	258
Overall Study Pharmacokinetic (PK) Population	0	277	241
Overall Study COMPLETED	212	222	205
Overall Study NOT COMPLETED	45	40	54

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received 2 placebo tablets: one placebo tablet matching 4 milligram (mg) baricitinib and one placebo tablet matching 2 mg baricitinib administered orally once daily (QD) for 52 weeks.	2 mg Baricitinib Participants received one 2 mg baricitinib tablet and one placebo tablet matching 4 mg baricitinib administered QD for 52 weeks.	4 mg Baricitinib Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.
Overall Study Adverse Event	15	10	16
Overall Study Death	3	0	4
Overall Study Lack of Efficacy	4	8	8
Overall Study Lost to Follow-up	2	1	3
Overall Study Withdrawal by Subject	18	14	21
Overall Study Withdrawal by Principal Investigator (PI)	1	1	1
Overall Study Sponsor's Decision	1	0	0
Overall Study Physician Decision	0	2	0
Overall Study Decreased Neutrophils due to Systemic Lupus Erythematosus (SLE)	0	1	0
Overall Study Protocol Violation	0	1	0
Overall Study Due to Epidemic/Pandemic	0	1	0
Overall Study Randomized but Never Treated	1	1	1

Baseline Characteristics

A Study of Baricitinib in Participants With Systemic Lupus Erythematosus (SLE-BRAVE II)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=256 Participants Participants received 2 placebo tablets: one placebo tablet matching 4 mg baricitinib and one placebo tablet matching 2 mg baricitinib administered orally QD for 52 weeks.	2 mg Baricitinib n=261 Participants Participants received one 2 mg baricitinib tablet and one placebo tablet matching 4 mg baricitinib administered QD for 52 weeks.	4 mg Baricitinib n=258 Participants Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.	Total n=775 Participants Total of all reporting groups
Age, Continuous	43.50 years STANDARD_DEVIATION 13.47 • n=5 Participants	42.80 years STANDARD_DEVIATION 12.99 • n=7 Participants	42.20 years STANDARD_DEVIATION 12.11 • n=5 Participants	42.80 years STANDARD_DEVIATION 12.86 • n=4 Participants
Sex: Female, Male Female	241 Participants n=5 Participants	246 Participants n=7 Participants	245 Participants n=5 Participants	732 Participants n=4 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	15 Participants n=7 Participants	13 Participants n=5 Participants	43 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants	11 Participants n=7 Participants	8 Participants n=5 Participants	28 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	40 Participants n=5 Participants	38 Participants n=7 Participants	40 Participants n=5 Participants	118 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	207 Participants n=5 Participants	212 Participants n=7 Participants	210 Participants n=5 Participants	629 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	14 Participants n=5 Participants	12 Participants n=7 Participants	13 Participants n=5 Participants	39 Participants n=4 Participants
Race (NIH/OMB) Asian	71 Participants n=5 Participants	66 Participants n=7 Participants	70 Participants n=5 Participants	207 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Black or African American	17 Participants n=5 Participants	23 Participants n=7 Participants	26 Participants n=5 Participants	66 Participants n=4 Participants
Race (NIH/OMB) White	145 Participants n=5 Participants	152 Participants n=7 Participants	140 Participants n=5 Participants	437 Participants n=4 Participants
Race (NIH/OMB) More than one race	5 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	13 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	12 Participants n=4 Participants
Region of Enrollment Argentina	34 Participants n=5 Participants	29 Participants n=7 Participants	29 Participants n=5 Participants	92 Participants n=4 Participants
Region of Enrollment Chile	8 Participants n=5 Participants	14 Participants n=7 Participants	12 Participants n=5 Participants	34 Participants n=4 Participants
Region of Enrollment Colombia	17 Participants n=5 Participants	15 Participants n=7 Participants	16 Participants n=5 Participants	48 Participants n=4 Participants
Region of Enrollment France	3 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Region of Enrollment India	32 Participants n=5 Participants	28 Participants n=7 Participants	34 Participants n=5 Participants	94 Participants n=4 Participants
Region of Enrollment Italy	2 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	9 Participants n=4 Participants
Region of Enrollment Japan	14 Participants n=5 Participants	12 Participants n=7 Participants	12 Participants n=5 Participants	38 Participants n=4 Participants
Region of Enrollment Philippines	13 Participants n=5 Participants	14 Participants n=7 Participants	11 Participants n=5 Participants	38 Participants n=4 Participants
Region of Enrollment Poland	26 Participants n=5 Participants	36 Participants n=7 Participants	31 Participants n=5 Participants	93 Participants n=4 Participants
Region of Enrollment Romania	12 Participants n=5 Participants	11 Participants n=7 Participants	7 Participants n=5 Participants	30 Participants n=4 Participants
Region of Enrollment Serbia	15 Participants n=5 Participants	20 Participants n=7 Participants	18 Participants n=5 Participants	53 Participants n=4 Participants
Region of Enrollment South Africa	14 Participants n=5 Participants	15 Participants n=7 Participants	12 Participants n=5 Participants	41 Participants n=4 Participants
Region of Enrollment South Korea	4 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	19 Participants n=4 Participants
Region of Enrollment Spain	12 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants	30 Participants n=4 Participants
Region of Enrollment United States	50 Participants n=5 Participants	50 Participants n=7 Participants	49 Participants n=5 Participants	149 Participants n=4 Participants

PRIMARY outcome

Timeframe: Week 52

Population: All randomized participants who received at least one dose of study drug (modified intent-to-treat (mITT) population). The hybrid imputation method \[nonresponder imputation (NRI) + multiple imputation (MI)\] was used to estimate the response rate in percentage and not the number of responder.

Outcome measures

Outcome measures
Measure	Placebo n=256 Participants Participants received 2 placebo tablets: one placebo tablet matching 4 mg baricitinib and one placebo tablet matching 2 mg baricitinib administered orally QD for 52 weeks.	4 mg Baricitinib n=258 Participants Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.	4 mg Baricitinib Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.
Percentage of Participants Achieving a Systemic Lupus Erythematosus Responder Index 4 (SRI-4) Response (4 mg Baricitinib)	45.6 percentage of participants	47.1 percentage of participants	—

SECONDARY outcome

Timeframe: Week 52

Population: All randomized participants who received at least one dose of study drug (mITT population). The hybrid imputation method \[nonresponder imputation (NRI) + multiple imputation (MI)\] was used to estimate the response rate in percentage and not the number of responder.

Outcome measures

Outcome measures
Measure	Placebo n=256 Participants Participants received 2 placebo tablets: one placebo tablet matching 4 mg baricitinib and one placebo tablet matching 2 mg baricitinib administered orally QD for 52 weeks.	4 mg Baricitinib n=261 Participants Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.	4 mg Baricitinib Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.
Percentage of Participants Achieving SRI-4 Response (2 mg Baricitinib)	45.6 percentage of participants	46.3 percentage of participants	—

SECONDARY outcome

Timeframe: Week 52

Population: All randomized participants who received at least 1 dose of study drug (mITT population). The hybrid imputation method \[nonresponder imputation (NRI) + multiple imputation (MI)\] was used to estimate the response rate in percentage and not the number of responder.

The LLDAS is a composite measure designed to identify patients achieving a state of low disease activity. The LLDAS response criteria were: (1) SLEDAI-2K \<=4, with no activity in major organ systems (CNS, vascular, renal, cardiorespiratory and constitutional); where "no activity" is defined as all items of SLEDAI-2K within these major organ systems equal to 0. (2) no new features of lupus disease activity compared to previous occurred visit, where the "new feature" is defined as any of the SLEDAI-2K 24 items changed from 0 to greater than 0; (3) PGA (scale 0-3), \<=1; (4) current prednisolone (or equivalent) dose \<=7.5 mg daily.

Outcome measures

Outcome measures
Measure	Placebo n=256 Participants Participants received 2 placebo tablets: one placebo tablet matching 4 mg baricitinib and one placebo tablet matching 2 mg baricitinib administered orally QD for 52 weeks.	4 mg Baricitinib n=261 Participants Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.	4 mg Baricitinib n=258 Participants Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.
Percentage of Participants Achieving a Lupus Low Disease Activity State (LLDAS)	23.2 percentage of participants	24.0 percentage of participants	25.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: All randomized participants who received at least one dose of study drug (mITT population).

Time to first severe flare analyzed using a Cox proportional hazards model with treatment group, baseline disease activity \[Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) \<10; SLEDAI-2K ≥10\], baseline corticosteroid dose (\<10 mg/day; ≥10 mg/day prednisone or equivalent), and region fitted as explanatory variables. Participants who did not have severe flare during the flare exposure time period were censored at the end of the flare exposure time.

Outcome measures

Outcome measures
Measure	Placebo n=256 Participants Participants received 2 placebo tablets: one placebo tablet matching 4 mg baricitinib and one placebo tablet matching 2 mg baricitinib administered orally QD for 52 weeks.	4 mg Baricitinib n=261 Participants Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.	4 mg Baricitinib n=258 Participants Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.
Time to First Severe Flare	NA weeks Data not available (NA) as \< 50% of participants experienced first flare, median was not reached, and 95% confidence interval could not be calculated.	NA weeks Data not available (NA) as \< 50% of participants experienced first flare, median was not reached, and 95% confidence interval could not be calculated.	NA weeks Data not available (NA) as \< 50% of participants experienced first flare, median was not reached, and 95% confidence interval could not be calculated.

SECONDARY outcome

Timeframe: Baseline, Week 40 through Week 52

Population: All randomized participants who received at least one dose of study drug (mITT population) and had received \>7.5 mg prednisone at baseline. Missing data was imputed using the hybrid imputation method \[NRI + mLOCF (modified last observation carried forward)\].

For the analysis of steroid use, steroid dosages were converted to a prednisone equivalent in mg. A responder was defined as having a prednisone reduction by \>=25% from Baseline to \<=7.5 mg/day during Weeks 40 through 52.

Outcome measures

Outcome measures
Measure	Placebo n=104 Participants Participants received 2 placebo tablets: one placebo tablet matching 4 mg baricitinib and one placebo tablet matching 2 mg baricitinib administered orally QD for 52 weeks.	4 mg Baricitinib n=114 Participants Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.	4 mg Baricitinib n=105 Participants Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.
Percentage of Participants Whose Average Prednisone Dose Had Been Reduced by >=25% From Baseline to <=7.5 mg/Day During Weeks 40 Through 52 in Participants Receiving Greater Than 7.5 mg/Day at Baseline	31.7 percentage of participants	29.8 percentage of participants	34.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: All randomized participants who received at least one dose of study drug (mITT population) and had baseline and post-baseline values at the specified time point. Missing data was imputed using the hybrid imputation method (NRI + MMRM).

Participants assessed the worst pain in the last 24 hours on an 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (pain as bad as you can imagine). The average worst daily pain score was calculated as the mean of the scores over the last 7 days prior to each assessment time point. Higher score indicated severe pain. Least Squares (LS) mean was calculated using Mixed Model Repeated Measures (MMRM) analysis with treatment, baseline disease activity (total SLEDAI-2K \<10; \>=10), baseline corticosteroid dose (\<10 mg/day; \>= 10 mg/day prednisone or equivalent), region (North America, Central/South, America/Mexico, Europe, Asia Rest of World), visit (as categorical variable), baseline value, treatment-by-visit interaction, and baseline value-by-visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=183 Participants Participants received 2 placebo tablets: one placebo tablet matching 4 mg baricitinib and one placebo tablet matching 2 mg baricitinib administered orally QD for 52 weeks.	4 mg Baricitinib n=182 Participants Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.	4 mg Baricitinib n=179 Participants Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.
Change From Baseline in Worst Pain Numeric Rating Scale (NRS)	-1.37 score on a scale Standard Error 0.14	-1.45 score on a scale Standard Error 0.14	-1.44 score on a scale Standard Error 0.14

SECONDARY outcome

Timeframe: Baseline, Week 52

FACIT-Fatigue score calculated according to a 13-item questionnaire that assess self reported fatigue and its impact upon daily activities and function. It uses a 5-point Likert-type scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse possible score) to 52 (best score). A higher score reflected an improvement in the participant's health status. Least Squares (LS) mean was calculated using Mixed Model Repeated Measures (MMRM) analysis with treatment, baseline disease activity (total SLEDAI-2K \<10; \>=10), baseline corticosteroid dose (\<10 mg/day; \>= 10 mg/day prednisone or equivalent), region (North America, Central/South, America/Mexico, Europe, Asia Rest of World), visit (as categorical variable), baseline value, treatment-by-visit interaction, and baseline value-by-visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=200 Participants Participants received 2 placebo tablets: one placebo tablet matching 4 mg baricitinib and one placebo tablet matching 2 mg baricitinib administered orally QD for 52 weeks.	4 mg Baricitinib n=203 Participants Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.	4 mg Baricitinib n=193 Participants Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Total Score	7.26 score on a scale Standard Error 0.60	6.90 score on a scale Standard Error 0.60	6.96 score on a scale Standard Error 0.61

SECONDARY outcome

Timeframe: Week 52

Population: All randomized participants who received at least one dose of study drug (mITT population) and had baseline CLASI score \>=10. Missing data was imputed using NRI method.

The CLASI is a single-page tool that separately quantifies disease activity and damage. For the activity score, points are given for the presence of erythema, scale, mucous membrane lesions, recent hair loss, and inflammatory alopecia. The total score represents the sum of the individual scores and ranges from 0 to 70. Higher scores are awarded for more severe manifestations.

Outcome measures

Outcome measures
Measure	Placebo n=59 Participants Participants received 2 placebo tablets: one placebo tablet matching 4 mg baricitinib and one placebo tablet matching 2 mg baricitinib administered orally QD for 52 weeks.	4 mg Baricitinib n=51 Participants Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.	4 mg Baricitinib n=50 Participants Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.
Percentage of Participants With Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Total Activity Score ≥10 at Baseline With ≥50% Reduction in CLASI Total Activity Score	66.1 percentage of participants	56.9 percentage of participants	58.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: All randomized participants who received at least one dose of study drug (mITT population) and had baseline and post-baseline values at the specified time point.

The number of tender and painful joints is determined by examination of 28 joints (14 on each side) which include: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. The joints are assessed and classified as tender or not tender. LS mean was calculated using Mixed Model Repeated Measures (MMRM) analysis with treatment, baseline disease activity (total SLEDAI-2K \<10; \>=10), baseline corticosteroid dose (\<10 mg/day; \>=10 mg/day prednisone or equivalent), region (North America, Central/South America/Mexico, Europe, Asia and Rest of World), visit (as categorical variable), baseline value, treatment-by-visit interaction, and baseline value-by-visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=200 Participants Participants received 2 placebo tablets: one placebo tablet matching 4 mg baricitinib and one placebo tablet matching 2 mg baricitinib administered orally QD for 52 weeks.	4 mg Baricitinib n=201 Participants Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.	4 mg Baricitinib n=190 Participants Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.
Change From Baseline in Tender Joint Count	-6.92 tender joint count Standard Error 0.301	-7.40 tender joint count Standard Error 0.300	-7.83 tender joint count Standard Error 0.306

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: All randomized participants who received at least one dose of study drug (mITT population) and had baseline and post-baseline values at the specified time point.

The number of swollen joints is determined by examination of 28 joints (14 on each side) which include: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. The joints are assessed and classified as swollen or not swollen. LS mean was calculated using MMRM analysis with treatment, baseline disease activity (total SLEDAI-2K \<10; \>=10), baseline corticosteroid dose (\<10 mg/day; \>=10 mg/day prednisone or equivalent), region (North America, Central/South America/Mexico, Europe, Asia and Rest of World), visit (as categorical variable), baseline value, treatment-by-visit interaction, and baseline value-by-visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=200 Participants Participants received 2 placebo tablets: one placebo tablet matching 4 mg baricitinib and one placebo tablet matching 2 mg baricitinib administered orally QD for 52 weeks.	4 mg Baricitinib n=201 Participants Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.	4 mg Baricitinib n=190 Participants Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.
Change From Baseline in Swollen Joint Count	-4.79 swollen joint count Standard Error 0.202	-5.10 swollen joint count Standard Error 0.201	-5.31 swollen joint count Standard Error 0.205

SECONDARY outcome

Timeframe: Week 0 (Baseline): 15 minutes (min) and 60 min postdose; Week 4: 2 to 4 hours (hr) postdose; Week 8: 4 to 6 hr postdose; Week 12 and Week 16 predose

Population: All randomized participants who received at least one dose of study drug with evaluable PK data.

AUCtau,ss reported for participants who received multiple doses of mg baricitinib was derived by a population pharmacokinetics approach.

Outcome measures

Outcome measures
Measure	Placebo n=277 Participants Participants received 2 placebo tablets: one placebo tablet matching 4 mg baricitinib and one placebo tablet matching 2 mg baricitinib administered orally QD for 52 weeks.	4 mg Baricitinib n=241 Participants Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.	4 mg Baricitinib Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.
Population Pharmacokinetics (PK): Area Under the Concentration-Time Curve for Dosing Interval of Baricitinib at Steady State (AUCtau,ss)	257 nanogramhour/milliliter (ngh/mL) Geometric Coefficient of Variation 48	505 nanogramhour/milliliter (ngh/mL) Geometric Coefficient of Variation 50	—

SECONDARY outcome

Timeframe: Week 0 (Baseline): 15 minutes (min) and 60 min postdose; Week 4: 2 to 4 hours (hr) postdose; Week 8: 4 to 6 hr postdose; Week 12 and Week 16 predose

Population: All randomized participants who received at least one dose of study drug with evaluable PK data.

PK: Maximum Concentration of Baricitinib at steady-state (Cmax,ss) was derived by a population pharmacokinetics approach.

Outcome measures

Outcome measures
Measure	Placebo n=277 Participants Participants received 2 placebo tablets: one placebo tablet matching 4 mg baricitinib and one placebo tablet matching 2 mg baricitinib administered orally QD for 52 weeks.	4 mg Baricitinib n=241 Participants Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.	4 mg Baricitinib Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.
Population PK: Maximum Observed Drug Concentration at Steady State (Cmax,ss)	27.0 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 23	54.1 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 24	—

Adverse Events

Placebo

Serious events: 26 serious events

Other events: 96 other events

Deaths: 3 deaths

2 mg Baricitinib

Serious events: 35 serious events

Other events: 100 other events

Deaths: 0 deaths

4 mg Baricitinib

Serious events: 32 serious events

Other events: 96 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=256 participants at risk Participants received 2 placebo tablets: one placebo tablet matching 4 mg baricitinib and one placebo tablet matching 2 mg baricitinib administered orally QD for 52 weeks.	2 mg Baricitinib n=261 participants at risk Participants received one 2 mg baricitinib tablet and one placebo tablet matching 4 mg baricitinib administered QD for 52 weeks.	4 mg Baricitinib n=258 participants at risk Participants received one 4 mg baricitinib tablet and one placebo tablet matching 2 mg baricitinib administered QD for 52 weeks.
Blood and lymphatic system disorders Neutropenia	2.7% 7/256 • Number of events 9 • Baseline through Follow-up (Up to 56 Weeks) All randomized participants who received at least one dose of study drug and who did not discontinue from the study for the reason 'Lost to Follow-up' at the first postbaseline visit (safety population). Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.9% 5/261 • Number of events 6 • Baseline through Follow-up (Up to 56 Weeks) All randomized participants who received at least one dose of study drug and who did not discontinue from the study for the reason 'Lost to Follow-up' at the first postbaseline visit (safety population). Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.0% 13/258 • Number of events 19 • Baseline through Follow-up (Up to 56 Weeks) All randomized participants who received at least one dose of study drug and who did not discontinue from the study for the reason 'Lost to Follow-up' at the first postbaseline visit (safety population). Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Diarrhoea	5.1% 13/256 • Number of events 14 • Baseline through Follow-up (Up to 56 Weeks) All randomized participants who received at least one dose of study drug and who did not discontinue from the study for the reason 'Lost to Follow-up' at the first postbaseline visit (safety population). Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	7.7% 20/261 • Number of events 25 • Baseline through Follow-up (Up to 56 Weeks) All randomized participants who received at least one dose of study drug and who did not discontinue from the study for the reason 'Lost to Follow-up' at the first postbaseline visit (safety population). Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	3.9% 10/258 • Number of events 11 • Baseline through Follow-up (Up to 56 Weeks) All randomized participants who received at least one dose of study drug and who did not discontinue from the study for the reason 'Lost to Follow-up' at the first postbaseline visit (safety population). Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Nasopharyngitis	9.0% 23/256 • Number of events 28 • Baseline through Follow-up (Up to 56 Weeks) All randomized participants who received at least one dose of study drug and who did not discontinue from the study for the reason 'Lost to Follow-up' at the first postbaseline visit (safety population). Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	6.9% 18/261 • Number of events 20 • Baseline through Follow-up (Up to 56 Weeks) All randomized participants who received at least one dose of study drug and who did not discontinue from the study for the reason 'Lost to Follow-up' at the first postbaseline visit (safety population). Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	8.1% 21/258 • Number of events 27 • Baseline through Follow-up (Up to 56 Weeks) All randomized participants who received at least one dose of study drug and who did not discontinue from the study for the reason 'Lost to Follow-up' at the first postbaseline visit (safety population). Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Upper respiratory tract infection	5.1% 13/256 • Number of events 16 • Baseline through Follow-up (Up to 56 Weeks) All randomized participants who received at least one dose of study drug and who did not discontinue from the study for the reason 'Lost to Follow-up' at the first postbaseline visit (safety population). Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	6.5% 17/261 • Number of events 18 • Baseline through Follow-up (Up to 56 Weeks) All randomized participants who received at least one dose of study drug and who did not discontinue from the study for the reason 'Lost to Follow-up' at the first postbaseline visit (safety population). Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	7.4% 19/258 • Number of events 22 • Baseline through Follow-up (Up to 56 Weeks) All randomized participants who received at least one dose of study drug and who did not discontinue from the study for the reason 'Lost to Follow-up' at the first postbaseline visit (safety population). Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Urinary tract infection	10.2% 26/256 • Number of events 32 • Baseline through Follow-up (Up to 56 Weeks) All randomized participants who received at least one dose of study drug and who did not discontinue from the study for the reason 'Lost to Follow-up' at the first postbaseline visit (safety population). Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	11.1% 29/261 • Number of events 36 • Baseline through Follow-up (Up to 56 Weeks) All randomized participants who received at least one dose of study drug and who did not discontinue from the study for the reason 'Lost to Follow-up' at the first postbaseline visit (safety population). Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	7.4% 19/258 • Number of events 26 • Baseline through Follow-up (Up to 56 Weeks) All randomized participants who received at least one dose of study drug and who did not discontinue from the study for the reason 'Lost to Follow-up' at the first postbaseline visit (safety population). Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Musculoskeletal and connective tissue disorders Back pain	2.3% 6/256 • Number of events 6 • Baseline through Follow-up (Up to 56 Weeks) All randomized participants who received at least one dose of study drug and who did not discontinue from the study for the reason 'Lost to Follow-up' at the first postbaseline visit (safety population). Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	3.1% 8/261 • Number of events 8 • Baseline through Follow-up (Up to 56 Weeks) All randomized participants who received at least one dose of study drug and who did not discontinue from the study for the reason 'Lost to Follow-up' at the first postbaseline visit (safety population). Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.8% 15/258 • Number of events 20 • Baseline through Follow-up (Up to 56 Weeks) All randomized participants who received at least one dose of study drug and who did not discontinue from the study for the reason 'Lost to Follow-up' at the first postbaseline visit (safety population). Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Nervous system disorders Headache	9.0% 23/256 • Number of events 26 • Baseline through Follow-up (Up to 56 Weeks) All randomized participants who received at least one dose of study drug and who did not discontinue from the study for the reason 'Lost to Follow-up' at the first postbaseline visit (safety population). Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	9.6% 25/261 • Number of events 28 • Baseline through Follow-up (Up to 56 Weeks) All randomized participants who received at least one dose of study drug and who did not discontinue from the study for the reason 'Lost to Follow-up' at the first postbaseline visit (safety population). Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	7.4% 19/258 • Number of events 21 • Baseline through Follow-up (Up to 56 Weeks) All randomized participants who received at least one dose of study drug and who did not discontinue from the study for the reason 'Lost to Follow-up' at the first postbaseline visit (safety population). Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Vascular disorders Hypertension	3.5% 9/256 • Number of events 9 • Baseline through Follow-up (Up to 56 Weeks) All randomized participants who received at least one dose of study drug and who did not discontinue from the study for the reason 'Lost to Follow-up' at the first postbaseline visit (safety population). Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.6% 12/261 • Number of events 13 • Baseline through Follow-up (Up to 56 Weeks) All randomized participants who received at least one dose of study drug and who did not discontinue from the study for the reason 'Lost to Follow-up' at the first postbaseline visit (safety population). Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.0% 13/258 • Number of events 14 • Baseline through Follow-up (Up to 56 Weeks) All randomized participants who received at least one dose of study drug and who did not discontinue from the study for the reason 'Lost to Follow-up' at the first postbaseline visit (safety population). Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 8005455979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60