Conflicting data on the effectiveness of the oral Janus kinase 1 and 2 inhibitor baricitinib in patients with systemic lupus erythematosus (SLE) come from a pair of phase 3 trials. In SLE-BRAVE I, the primary efficacy endpoint was met for participants taking 4-mg doses of baricitinib. However, SLE-BRAVE II failed to replicate those results with baricitinib doses of 2 mg or 4 mg.
Both studies included adult participants with active SLE receiving stable background therapy who were randomly assigned to baricitinib 4 mg, 2 mg, or placebo once daily for 52 weeks with standard-of-care therapy. The primary endpoint in the trials was the proportion of patients reaching an SLE Responder Index (SRI)-4 response at week 52 in the baricitinib 4 mg treatment group compared with placebo.
SLE-BRAVE I Results: “760 participants were randomly assigned and received at least one dose of baricitinib 4 mg (n = 252), baricitinib 2 mg (n = 255), or placebo (n = 253). A significantly greater proportion of participants who received baricitinib 4 mg (142 [57%]; odds ratio 1.57 [95% CI 1.09 to 2.27]; difference with placebo 10.8 [2.0 to 19.6]; P = 0.016), but not baricitinib 2 mg (126 [50%]; 1 14 [0.79 to 1.65]; 3.9 [–4.9 to 12.6]; P = 0.47), reached SRI-4 response compared with placebo (116 [46%]). There were no significant differences between the proportions of participants in either baricitinib group reaching any of the major secondary endpoints compared with placebo, including glucocorticoid tapering and time to first severe flare. 26 (10%) participants receiving baricitinib 4 mg had serious adverse events, 24 (9%) participants receiving baricitinib 2 mg, and 18 (7%) participants receiving placebo. The safety profile of baricitinib in participants with SLE was consistent with the known baricitinib safety profile.”
SLE-BRAVE II Results: “A total of 775 patients were randomly assigned and received at least one dose of baricitinib 4 mg (n = 258), baricitinib 2 mg (n = 261), or placebo (n = 256). There was no difference in the primary efficacy outcome of the proportion of SRI-4 responders at week 52 between participants who received baricitinib 4 mg (121 [47%]; odds ratio 1.07 [95% CI 0.75 to 1.53]; difference with placebo 1.5 [95% CI –7.1 to 10.2]), 2 mg (120 [46%]; 1.05 [0.73 to 1.50]; 0.8 [–7.9 to 9.4]) and placebo (116 [46%]). None of the major secondary endpoints, including glucocorticoid tapering and time to first severe flare, were met. Serious adverse events were observed in 29 (11%) participants in the baricitinib 4 mg group, 35 (13%) in the baricitinib 2 mg group, and 22 (9%) in the placebo group. The safety profile of baricitinib in patients with SLE was consistent with the known baricitinib safety profile.”