Baricitinib produces mixed results in pair of BRAVE lupus trials
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Baricitinib met the primary endpoint in one phase 3 study of patients with systemic lupus erythematosus, but failed to meet the same endpoint in a second trial aiming to repeat the results, according to data published in The Lancet.
“This is the phase 3 trial of baricitinib in active SLE that was prompted by the positive results in the earlier phase 2 trial and strong biological evidence for JAK inhibition in lupus,” Eric F. Morand, MBBS, of Monash Health in Australia, who was the lead author of the SLE-BRAVE-I trial, as well as co-author of the SLE-BRAVE-II trial, told Healio. “There were two parallel phase 3 studies that were both global trials.”
SLE-BRAVE-1 and SLE-BRAVE-II were both double-blind, randomized, placebo-controlled trials investigating the safety and efficacy of baricitinib (Olumiant, Eli Lilly & Co.) in patients with SLE. Both studies included patients aged 18 years or older who had SLE and were receiving stable background therapy. Patients in both studies were randomized 1:1:1 to receive either baricitinib 4 mg or 2 mg, or placebo.
The primary endpoint in both trials was the percentage of patients receiving 4 mg baricitinib who achieved an SLE Responder Index (SRI)-4 response at week 52 compared with placebo. In addition, the researchers in both trials conducted safety analyses for any patients who received baricitinib and did not discontinue therapy during the study period. Secondary endpoints differed between the studies, but included percentages of patients who achieved low disease activity and who received doses of prednisone.
A total of 760 patients participated in SLE-BRAVE-1, 252 of whom received baricitinib 4 mg, while 255 received 2 mg doses and 253 received placebo. Compared with placebo, “significantly more” patients achieved the primary endpoint (OR = 1.57; 95% CI, 1.09-2.27) with baricitinib 4 mg, according to the researchers. However, there was no statistically significant difference between either baricitinib group and placebo regarding secondary endpoints. The safety profile remained consistent with previous findings, the researchers wrote.
SLE-BRAVE-II, meanwhile, included 775 patients. In this study, 258 patients received baricitinib 4 mg, 261 patients received 2 mg baricitinib, and 256 patients received placebo. Here, there were no differences in the percentage of patients from each group achieving the primary endpoint, according to the researchers. In addition, no secondary endpoints were met. However, the trial was in line with previously reported safety findings.
“BRAVE-I was a positive trial with a significant difference in favor of baricitinib on the primary outcome measure of SRI(4),” Morand said. “While exploratory secondary outcome measures in musculoskeletal and mucocutaneous domain scores were also positive, formal secondary outcomes were not. The companion BRAVE-II trial was negative. This means that evidence supporting efficacy of baricitinib in SLE is insufficient to support registration. Importantly, no new safety signals were seen in this higher risk population.
“Challenges translating positive phase 2 trial results to phase 3 and subsequent approval remain,” he added. “A global project seeking to produce improved outcome measures for SLE trials may make a major difference in this space. In the meantime, several other promising programs are in phase 3 and we hold out hope for positive results and more new medicines for our patients.”
References:
Petri M, et al. Lancet. 2023:doi:10.1016/S0140-6736(22)02546-6
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