POS0190 EFFICACY AND SAFETY OF BARICITINIB IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: RESULTS FROM TWO RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP, PHASE 3 STUDIES

Abstract

BackgroundIn a 24-week, phase 2 clinical study (NCT02708095) in patients with systemic lupus erythematosus (SLE), baricitinib (BARI), an oral selective inhibitor of Janus kinase 1 and 2 approved for the treatment of rheumatoid arthritis and atopic dermatitis, inhibited the type l interferon gene signature, multiple other cytokine pathways, and improved disease activity (1) (2).ObjectivesTo further evaluate the efficacy and safety of BARI in patients with SLE.MethodsPatients with active SLE receiving stable background therapy were randomised 1:1:1 to BARI 2-mg, 4-mg, or placebo (PBO) once daily in two identically designed, 52-week, phase 3 randomised, PBO-controlled studies. In SLE-BRAVE-I (NCT03616912) and -II (NCT03616964), 760 and 775 patients, respectively were enrolled in a balanced manner across regions, although different countries per region participated in each study. The primary endpoint for both studies was the proportion of patients achieving an SLE Responder Index-4 (SRI-4) response at week 52. Glucocorticoid tapering was encouraged but not required per protocol.ResultsThe mean Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) at baseline was 10.1 for both SLE-BRAVE-I and -II participants; musculoskeletal and mucocutaneous domains were the most common domains involved at baseline. In SLE-BRAVE-I, the proportion of SRI-4 responders at week 52 among patients treated with BARI 4-mg (56.7%), but not BARI 2-mg (49.8%), was significantly greater than in patients treated with PBO (45.9%, p = 0.016) (Table 1). No difference was seen in SLE-BRAVE-II (47.1%, 46.3%, and 45.6%, BARI 4-mg, 2-mg, and PBO, respectively). None of the key secondary endpoints, including glucocorticoid tapering or time to first severe flare (SFI), were met in either study. The proportions of patients with serious adverse events (SAEs) were 7.1% and 8.6% for PBO, 9.4% and 13.4% for BARI 2-mg and 10.3% and 11.2% for BARI 4-mg in SLE-BRAVE-I and II, respectively.Table 1.Efficacy and safety of baricitinib in patients with SLE-BRAVE-I and -IISLE-BRAVE-ISLE-BRAVE-IIEfficacy measurePBO (N=253)BARI 2-mg (N=255)BARI 4-mg (N=252)PBO (N=256)BARI 2-mg (N=261)BARI 4-mg (N=258)SRI-4 (W52)116 (45.9)126 (49.8)142 (56.7)*116 (45.6)120 (46.3)121 (47.1)SRI-4 (W24)99 (39.1)114 (44.8)117 (46.5)98 (38.6)104 (40.0)108 (42.1)Severe Flares (n, events)38 (15.0)34 (13.3)26 (10.3)26 (10.2)29 (11.1)29 (11.2)HR for time to first severe flare (SFI) HR [CI]NA0.8 [0.52, 1.32]0.65 [0.40, 1.08]NA1.1 [0.65, 1.89]1.1 [0.67, 1.94]Glucocorticoid sparing36 (30.8)31 (29.2)36 (34.0)33 (31.7)34 (29.8)36 (34.3)LLDAS (W52)66 (26.2)65 (25.7)74 (29.7)59 (23.2)62 (24.0)65 (25.4)Safety measureTEAE210 (83.0)210 (82.4)208 (82.5)198 (77.3)199 (76.2)200 (77.5)SAE18 (7.1)24 (9.4)26 (10.3)22 (8.6)35 (13.4)29 (11.2)Data are n (%) patients, unless otherwise indicated. BARI=baricitinib; CI=confidence interval; HR=hazard ratio compared with PBO; LLDAS=lupus low disease activity state; N=number of patients in the analysis population; n=number of patients in the specified category; PBO=placebo; TEAE=treatment-emergent adverse event; SAE=serious adverse event; W=week. *p≤0.05 vs PBO.ConclusionAlthough phase 2 data suggested BARI as a potential treatment for patients with SLE (2), the SLE-BRAVE-I and -II phase 3 study results were discordant for the primary outcome measure, with only SLE-BRAVE-I positive, making it difficult to elucidate benefit. Additional analyses are being performed to understand this discordance. No new safety signals were observed.