Clinical outcomes of baricitinib in patients with systemic lupus erythematosus: Pooled analysis of SLE-BRAVE-I and SLE-BRAVE-II trials

Abstract

Background Baricitinib is an oral selective inhibitor of Janus kinase 1/2 that has achieved clinically meaningful outcomes for systemic lupus erythematosus (SLE). Only two phase 3 randomized clinical trials (SLE-BRAVE-I and SLE-BRAVE-II) have been completed, but their conclusions were inconsistent. We aimed to determine the efficacy and safety of once-daily oral baricitinib 4 mg or 2 mg treatment versus placebo in participants with active SLE. Methods SLE-BRAVE-I and SLE-BRAVE-II are two multicenter, placebo-controlled, double-blind, phase 3 randomized clinical trials with follow-up to 52 weeks. At baseline, 1535 patients (aged ≥18 years) with active SLE (excluding those with central nervous system and severe active renal disease) receiving stable background therapy were randomly assigned 1:1:1 to baricitinib 4 mg, baricitinib 2 mg, or placebo once daily for 52 weeks. The primary endpoint was the proportion of patients with an SLE Responder Index (SRI)-4 response at week 52 in the baricitinib 4 mg treatment group compared with placebo. Results There was no difference in the primary efficacy outcome of the proportion of SRI-4 responders at week 52 between participants who received baricitinib 4mg (263 [52%]; odds ratio (OR) 1.27 [95% CI 0.99, 1.63]), 2 mg (246 [48%]; 1.09 [0.85, 1.39]) and placebo (232 [46%]). However, based on SLE-BRAVE-I and SLE-BRAVE-II studies, baricitinib 4 mg and baricitinib 2 mg were more effective in reducing the disease activity in participants who treated with a glucocorticoid dose at baseline of 10mg per day or higher of prednisone or equivalent, and baricitinib 4mg was more effective in reducing the disease activity in participants with highly active disease (SLEDAI-2K score at baseline >10). None of the major secondary endpoints, including time to first severe flare and glucocorticoid tapering, were met. Compared with placebo, baricitinib 4mg and baricitinib 2mg in the treatment of SLE did not increase the incidence of treatment-emergent adverse events (TEAEs). Conclusions Pooled analysis showed that once-daily oral baricitinib 4mg or baricitinib 2mg in addition to SOC did not reduce the overall disease activity compared with placebo although they were safe for SLE. However, baricitinib might be a potential treatment option for SLE in certain subpopulation, such as in participants who received a glucocorticoid dose at baseline of 10mg per day or higher of prednisone or equivalent (baricitinib 4mg and baricitinib 2mg) and in participants with highly active disease (SLEDAI-2K score at baseline >10) (baricitinib 4mg).