medwireNews: Discordant results from two phase 3 studies make it difficult to determine whether baricitinib benefits patients with systemic lupus erythematosus (SLE), despite previous positive findings in phase 2.
Eric Morand (Monash University, Melbourne, Australia) presented his team’s evaluation of two identically designed phase 3 studies – SLE-BRAVE-I (NCT03616912) and SLE-BRAVE-II (NCT03616964) – in a poster at the EULAR 2022 Congress in Copenhagen, Denmark.
The randomized, double-blind studies evaluated SRI-4 response at 52 weeks in patients with autoantibody-positive, active SLE given one of two doses of baricitinib (2 or 4 mg/day) or placebo. The studies were conducted following a 24-week phase 2 trial that showed clinical improvement with the selective Janus kinase 1 and 2 inhibitor in such patients.
The patients were stratified based on baseline disease activity, prednisolone dose, and geographic region, and were allowed to continue background standard-of-care medications, “but glucocorticoid taper was strongly encouraged with a goal of 7.5 mg of prednisolone or less by week 40,” Morand reported.
Baseline characteristics were well balanced across the two treatment groups and were typical for phase 3 studies in SLE, noted Morand. More than 90% of participants were women, the average age was 40 years, the average disease duration was 7 to 8 years, and the average SLEDAI-2K score was 10 points, with half of the patients scoring above 10. Three-quarters of patients were taking glucocorticoids and more than half were taking immunosuppressants.
The primary endpoint was achieved in SLE-BRAVE-I, with 56.7% of the 252 patients receiving the higher 4 mg baricitinib dose achieving an SRI-4 response at week 52, compared with 45.9% of 253 patients given placebo; a significant difference.
“In contrast, although the study design was identical, the primary endpoint was not achieved in SLE-BRAVE-II,” Morand highlighted. The 258 patients taking baricitinib 4 mg and the 256 given placebo had similar SRI-4 response rates, at 47.4% and 45.6%, respectively.
Key secondary endpoints, such as SRI-4 response at week 24, time to first severe flare, glucocorticoid sparing, and achievement of Lupus Low Disease Activity State, were not met in either study. And while significant improvements in musculoskeletal and mucocutaneous domains on both SLEDAI-K and BILAG were seen with baricitinib 4 mg versus placebo in SLE-BRAVE-I, this was not the case for SLE-BRAVE-II.
Serious infections were increased in baricitinib-treated patients, noted Morand, but “importantly there was no increase in venous thromboembolism events in baricitinib-treated groups.” He added that the safety profile of baricitinib in patients with SLE on background therapy was “otherwise consistent with the known profile of this drug.”
Morand concluded that “evidence for the efficacy of baricitinib in SLE remains inconclusive.”
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EULAR 2022; Copenhagen, Denmark: 1–4 June
Ann Rheum Dis 2022; 81: 327–328