Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 3 trial (SLE-BRAVE-II).

Autor:	Petri M; Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: mpetri@jhmi.edu., Bruce IN; Centre for Epidemiology Versus Arthritis, University of Manchester, Manchester, UK; National Institute for Health Research Manchester Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK., Dörner T; Department of Rheumatology and Clinical Immunology, Charite Universitätsmedizin Berlin, Berlin, Germany; Deutsches Rheumaforschungszentrum, Berlin, Germany., Tanaka Y; University of Occupational and Environmental Health, Japan, Kitakyushu, Japan., Morand EF; Centre for Inflammatory Disease, Monash University, Melbourne, VIC, Australia., Kalunian KC; Division of Rheumatology, University of California San Diego School of Medicine, La Jolla, CA, USA., Cardiel MH; Centro de Investigación Clínica de Morelia SC, Morelia, Michoacán, Mexico., Silk ME; Eli Lilly and Company, Indianapolis, IN, USA., Dickson CL; Eli Lilly and Company, Indianapolis, IN, USA., Meszaros G; Eli Lilly and Company, Indianapolis, IN, USA., Zhang L; Eli Lilly and Company, Indianapolis, IN, USA., Jia B; Eli Lilly and Company, Indianapolis, IN, USA., Zhao Y; Eli Lilly and Company, Indianapolis, IN, USA., McVeigh CJ; Eli Lilly and Company, Indianapolis, IN, USA., Mosca M; Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Jazyk:	angličtina
Zdroj:	Lancet (London, England) [Lancet] 2023 Mar 25; Vol. 401 (10381), pp. 1011-1019. Date of Electronic Publication: 2023 Feb 24.
DOI:	10.1016/S0140-6736(22)02546-6
Abstrakt:	Background: Baricitinib is an oral selective inhibitor of Janus kinase 1 and 2 approved for the treatment of rheumatoid arthritis, atopic dermatitis, and alopecia areata. In a 24-week phase 2 study in patients with systemic lupus erythematosus (SLE), baricitinib 4 mg significantly improved SLE disease activity compared with placebo. In this Article, we report the evaluation of efficacy and safety of baricitinib in patients with SLE in a 52-week phase 3 study. Methods: In this phase 3 double-blind, randomised, placebo-controlled study, SLE-BRAVE-II, patients (aged ≥18 years) with active SLE receiving stable background therapy were randomly assigned 1:1:1 to baricitinib 4 mg, baricitinib 2 mg, or placebo once daily for 52 weeks. The primary endpoint was the proportion of patients with an SLE Responder Index (SRI)-4 response at week 52 in the baricitinib 4 mg treatment group compared with placebo. Glucocorticoid tapering was encouraged but not required per protocol. The primary endpoint was assessed by logistic regression analysis with baseline disease activity, baseline corticosteroid dose, region, and treatment group in the model. Efficacy analyses were done on an intention-to-treat population, comprising all participants who were randomly assigned and received at least one dose of investigational product and who did not discontinue from the study for the reason of lost to follow-up at the first post-baseline visit. Safety analyses were done on all randomly assigned participants who received at least one dose of investigational product and who did not discontinue. This study is registered with ClinicalTrials.gov, NCT03616964, and is complete. Findings: 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 4mg (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. Interpretation: Although phase 2 data suggested baricitinib as a potential treatment for patients with SLE, which was supported in SLE-BRAVE-I, this result was not replicated in SLE-BRAVE-II. No new safety signals were observed. Funding: Eli Lilly and Company. Competing Interests: Declaration of interests MP has received research grants from Eli Lilly and Company and has participated on a data safety monitoring board or advisory board for Eli Lilly and Company. INB has received grant or research support from GSK and Janssen; received consulting and speaking fees from AstraZeneca, BristolMeyersSquibb, and UCB; received consulting and honoraria from GSK; and received consulting fees from Aurinia and Eli Lilly and Company. TD has received financial support for clinical studies (paid to the university) from AbbVie, BristolMeyersSquibb, Eli Lilly and Company, Janssen, Novartis, and UCB; and honoraria for scientific advice from AbbVie, BMS, Eli Lilly and Company, Novartis, and UCB. YT has received speaking fees or honoraria from Boehringer-Ingelheim, Eli Lilly and Company, Abbvie, Gilead, AstraZeneca, BristolMeyersSquibb, Chugai, Daiichi-Sankyo, Eisai, Pfizer, Mitsubishi-Tanabe, and GSK; and has received research grants from Asahi-Kasei, Abbvie, Chugai, Eisai, Takeda, Daiichi-Sankyo, and Behringer-Ingelheim. EFM has received research grants from Janssen, AbbVie, Amgen, AstraZeneca, Biogen, BristolMyersSquibb, Eli Lilly and Company, EMD Serono, Genentech, GSK, and UCB; and consulting fees from Amgen, AstraZeneca, Biogen, BristolMyersSquibb, Capella, and Eli Lilly and Company. MHC is a researcher, speaker, or adviser for Abbvie, Eli Lilly and Company, Gilead Sciences, GSK, Pfizer, and Janssen. MES, CLD, GM, LZ, BJ, YZ, and CJM are employees and shareholders of Eli Lilly and Company. MM has received consulting fees or honoraria, and participated on a data safety monitoring board or advisory board for AstraZeneca, Eli Lilly and Company, and GSK; and received payment for expert testimony from GSK. KCK declares no competing interests. (Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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