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

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).

Time frame: 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.

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.

Time frame: 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).

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.

Time frame: 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.

Time frame: 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.

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.

Time frame: 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).

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.

Time frame: 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.

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).

Time frame: 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.

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.

Time frame: 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 \[NRI + mLOCF (modified last observation carried forward)\].

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.

Time frame: 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.

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

Time frame: 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.

Time frame: 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.

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.

Time frame: Baseline to Week 52

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