Results of BRAVE lupus trials on baricitinib for SLE patients

According to a recent study published in The Lancet, baricitinib achieved the primary endpoint in a phase 3 trial involving patients with systemic lupus erythematosus (SLE), but failed to achieve the same endpoint in a second trial intended to confirm the findings.

Dr. Morand and his co-researchers conducted the multicenter, double-blind, randomized, placebo-controlled, parallel-group, phase 3 study called SLE-BRAVE-I to evaluate the safety of baricitinib in SLE patients. A total of 760 patients were randomized to receive either 4 mg or 2 mg of baricitinib or a placebo. Compared to the placebo group (46%), a significantly higher percentage of subjects who took 4 mg of baricitinib (57%) experienced an SLE Responder Index (SRI)-4 response (odds ratio [OR] 1.57; the difference with control 10.8; p=0.016). However, this was not observed in the 2 mg baricitinib group (50%; OR 1.14; control OR 3.9; p=0.47). The percentage of participants in either baricitinib group achieving important secondary goals, such as glucocorticoid tapering and time to first severe flare, did not differ significantly from the placebo group. Serious side effects were observed in 10% of participants taking 4 mg of baricitinib, 9% of those taking 2 mg of baricitinib, and 7% of those taking a placebo.

2018 double-blind, multicenter, randomized, placebo-controlled, phase 2 study also reported the safety profile and efficacy of baricitinib in SLE patients. During week 24, 67% of 104 patients receiving baricitinib 4 mg (OR vs. placebo 1.8, p=0.0414) and 58% of 105 patients receiving baricitinib 2 mg (OR 1.3, p=0.39) had resolution of their SLEDAI-2K arthritis or rash. The placebo group had adverse events in 65% of patients, while 71% and 73% of patients in the baricitinib 2 mg and 4 mg groups, respectively, had adverse events. With a safety profile comparable to prior baricitinib studies, the 4 mg dose of baricitinib effectively reduced the signs and symptoms of active SLE in poorly controlled patients, despite standard-of-care medication.

Overall, these findings suggest that baricitinib may be a potential treatment option for SLE patients, but further studies are needed to assess long-term safety and efficacy. This research lays the groundwork for upcoming trials of JAK1/2 inhibition in combination with baricitinib as a novel oral treatment option for SLE.

References

  1. Morand EF, Vital EM, Petri M, van Vollenhoven R, Wallace DJ, Mosca M, Furie RA, Silk ME, Dickson CL, Meszaros G, Jia B. Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 3 trial (SLE-BRAVE-I). The Lancet. 2023 Mar 25;401(10381):1001-10.
  2. Wallace DJ, Furie RA, Tanaka Y, Kalunian KC, Mosca M, Petri MA, Dörner T, Cardiel MH, Bruce IN, Gomez E, Carmack T. Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 2 trial. The Lancet. 2018 Jul 21;392(10143):222-31.
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