Background Baricitinib is an oral, reversible, selective Janus kinase 1 and 2 inhibitor.
Methods In this phase III, double-blind 24-week study, 684 biologic disease-modifying antirheumatic drug (DMARD)-naïve patients with rheumatoid arthritis and inadequate response or intolerance to ≥1 conventional synthetic DMARDs were randomly assigned 1:1:1 to placebo or baricitinib (2 or 4 mg) once daily, stratified by region and the presence of joint erosions. Endpoint measures included American College of Rheumatology 20% response (ACR20, primary endpoint), Disease Activity Score (DAS28) and Simplified Disease Activity Index (SDAI) score ≤3.3.
Results More patients achieved ACR20 response at week 12 with baricitinib 4 mg than with placebo (62% vs 39%, p≤0.001). Compared with placebo, statistically significant improvements in DAS28, SDAI remission, Health Assessment Questionnaire-Disability Index, morning joint stiffness, worst joint pain and worst tiredness were observed. In a supportive analysis, radiographic progression of structural joint damage at week 24 was reduced with baricitinib versus placebo. Rates of adverse events during the treatment period and serious adverse events (SAEs), including serious infections, were similar among groups (SAEs: 5% for baricitinib 4 mg and placebo). One patient had an adverse event of tuberculosis (baricitinib 4 mg); one patient had an adverse event of non-melanoma skin cancer (baricitinib 4 mg). Two deaths and three major adverse cardiovascular events occurred (placebo). Baricitinib was associated with a decrease in neutrophils and increases in low-density and high-density lipoprotein.
Conclusions In patients with rheumatoid arthritis and an inadequate response or intolerance to conventional synthetic DMARDs, baricitinib was associated with clinical improvement and inhibition of progression of radiographic joint damage.
Trial registration number NCT01721057; Results.
- Rheumatoid Arthritis
- DMARDs (synthetic)
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Handling editor Tore K Kvien
Correction notice This article has been corrected since it published Online First. The affiliation for Dr Chen has been corrected.
Contributors MD was the principal investigator, the designated signatory of the clinical study report and wrote the first draft of the discussion. SdB wrote the first draft of the introduction and results. All authors participated in the analyses and interpretation of data, provided critical comments and input and reviewed and approved the final manuscript. The authors would like to thank Stephanie Colvin, PhD of Eli Lilly and Company for creating the tables and figures and for assisting with manuscript preparation and process support.
Funding This study was funded by Eli Lilly and Company and Incyte Corporation.
Competing interests MD has received grant/research support or consulting support from AbbVie, Bristol Myers Squibb, Eli Lilly and Company, Novartis, Pfizer, Roche, Sanofi and UCB. PE has received grant/research support or consulting support from Abbott, AbbVie, Bristol Myers Squibb, Eli Lilly and Company, MSD, Novartis, Pfizer, Roche, Samsung, Takeda and UCB. DvdH has received grant/research support and/or consulting fees from AbbVie, Amgen, AstraZeneca, Augurex, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli Lilly and Company, Galapagos, Glaxo-Smith Kline, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi, UCB and Vertex and is director of Imaging Rheumatology bv. Y-CC has received speakers bureau fees and/or grant research support from AbbVie, Bristol Myers Squibb, Eli Lilly and Company and Pfizer. MG received research support from Eli Lilly and Company. JL, SB, SW, IdlT, CG, TR, DS and SdB are employees of Eli Lilly and Company and may own stock or stock options in Eli Lilly and Company.
Ethics approval The study was conducted in accordance with the ethical principles of the Declaration of Helsinki and Good Clinical Practice guidelines and was approved by the institutional review board or ethics committee of each centre.
Provenance and peer review Not commissioned; externally peer reviewed.