Chu Review: Petri 2023’s SLE-BRAVE-II trial of Baricitinib for SLE

Petri, et al. 2023. Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 3 trial (SLE-BRAVE-II). The Lancet, 401, 10381, p1011-1019.

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02546-6/fulltext

One Liner: Baricinitib unfortunately failed to meet its primary outcomes for SLE in this negative follow-up study; will not change my practice.

Brief Summary

• Clinical Question (PICO): In pts with active SLE who take the intervention of baricitinib 4 mg + SOC, compared to placebo + SOC, is there improved outcomes in [primary] proportion of pts reaching an SRI-4 response at 52 wks, and some secondary outcomes similar to the SLE-BRAVE-I trial.
• This was meant to be a follow-up to the SLE-BRAVE-I to further tease out safety and efficacy, with similar study patient population demographics, inclusion, exclusion, primary, and secondary outcomes.
• While there were very few serious adverse events, unfortunately the primary outcome was not met, and this medication is being “retired” from SLE research.

Chu Review: Morand 2023’s SLE-BRAVE-I trial, Baricitinib for SLE

This was one of the first RCT’s for a medication completely outside of typical ER that I looked into, mostly out of curiosity, partially because I had just discovered that I had institutional access at the time to The Lancet, and also because my patient population at the time I read this paper was absolutely saturated in people with rheumatologic disease. This paper, and also the follow up SLE-BRAVE-II trial papers, were certainly a lesson to me in interpretation of results and “how investigational medications/therapies/etc. papers are written,” compared to, say, a systematic review, retrospective review, etc. While unfortunately baricitinib didn’t bear out for SLE treatment in the follow up SLE-BRAVE-II trial, reading this paper was good practice for me, to be honest.

Morand, et al. 2023. Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 3 trial (SLE-BRAVE-I). The Lancet, 401, 10381, p1001-1010.

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02607-1/fulltext

One Liner: Baricitinib 4 mg, an immunosuppressant, shows promise for SLE symptoms compared to placebo; will not change my practice because I don’t prescribe it.

Brief Summary:

• Clinical Question (PICO): For patients that have active SLE receiving standard of care (SOC; e.g. immunomodulators, steroids), does the intervention of baricitinib, compared to placebo, lead to improved outcomes as measured by [primary] an SRI-4 response at 52 weeks in the 4 mg group and some other secondary outcomes related to specific scoring and ability to lower steroids.
• Pts were mainly Caucasian women in their 40’s with similar baseline characteristics and SLE involvement. Pts were randomly put 1:1:1 into placebo, 2 mg, and 4 mg of baricitinib.
• Exclusion criteria included severe SLE lupus nephritis or CNS involvement, or use of belimumab or anifrolumab. Pts were allowed to maintain other SOC rx, e.g. antimalarial, immunosuppressant, and steroids.
• About 57% of pts met the primary endpoint. No statistical significance in meeting any secondary outcomes. There may have been some improvement in MSK and mucocutaneous symptoms.
• Similar rates of adverse events, incl major adverse cardiovascular events, thromboembolism, stroke, and opportunistic infections (which were all very low regardless) across groups.
• Unfortunately, the SLE-BRAVE-II trial results, which were published not long thereafter, didn’t bear out. See that review post for further details.
• Will not change my practice since I don’t prescribe it as an ER doc.