Objectives This study investigated the effects of dose step-down in patients with rheumatoid arthritis (RA) who achieved sustained disease control with baricitinib 4 mg once a day.
Methods Patients who completed a baricitinib phase 3 study could enter a long-term extension (LTE). In the LTE, patients who received baricitinib 4 mg for ≥15 months and maintained CDAI low disease activity (LDA) or remission (REM) were blindly randomised to continue 4 mg or taper to 2 mg. Patients could rescue (to 4 mg) if needed. Efficacy and safety were assessed through 48 weeks.
Results Patients in both groups maintained LDA (80% 4 mg; 67% 2 mg) or REM (40% 4 mg; 33% 2 mg) over 48 weeks. However, dose reduction resulted in small, statistically significant increases in disease activity at 12, 24 and 48 weeks. Dose reduction also produced earlier and more frequent relapse (loss of step-down criteria) over 48 weeks compared with 4 mg maintenance (23% 4 mg vs 37% 2 mg, p=0.001). Rescue rates were 10% for baricitinib 4 mg and 18% for baricitinib 2 mg. Dose reduction was associated with a numerically lower rate of non-serious infections (30.6 for baricitinib 4 mg vs 24.9 for 2 mg). Rates of serious adverse events and adverse events leading to discontinuation were similar across groups.
Conclusions In a large randomised, blinded phase 3 study, maintenance of RA control following induction of sustained LDA/REM with baricitinib 4 mg was greater with continued 4 mg than after taper to 2 mg. Nonetheless, most patients tapered to 2 mg could maintain LDA/REM or recapture with return to 4 mg if needed.
- rheumatoid arthritis
- DMARDs (synthetic)
- disease activity
- DMARDs (biologic)
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Handling editor Francis Berenbaum
Presented at This work has been presented at the 2017 American College of Rheumatology Annual Meeting, 3–8 November 2017, San Diego, California (Takeuchi T, Genovese MC, Haraoui B, Li Z, Xie L, Klar R, Pinto Correia A, Otawa S, Lopez-Romero P, de la Torre I, Rooney TP, Smolen JS. Dose reduction of baricitinib in patients with rheumatoid arthritis achieving sustained disease control: results of a prospective study [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10)).
Contributors All authors have contributed to drafting and revising the manuscript and supplemental material documents to respond point-by-point to journal reviewers' comments.
Funding This study was funded by Eli Lilly and Company and Incyte.
Competing interests TT has received consulting support and/or speakers’ bureau fees from AbbVie GK, Asahi Kasei Medical KK, Astellas Pharma, AstraZeneca KK, Bristol-Myers KK, Celtrion, Chugai Pharma, Daiichi Sankyo, Eisai, Eli Lilly and Company, Janssen Pharma KK, Merck Serono, Mitsubishi Tanabe Pharma, Nipponkayaku, Novartis Pharma KK, Pfizer Japan, Takeda Pharma and UCB Japan. MCG has received grant/research support and/or consulting support from AbbVie, Astellas, Eli Lilly and Company, Galapagos, Gilead, Pfizer and Vertex. BH has received grant/research support, consulting fees and/or speakers’ bureau fees from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Pfizer, Roche and UCB. ZL has nothing to disclose. LX, APC, SO, PRL, IdlT, TPR, and WM are employees of Eli Lilly and Company and may own stock or stock options in Eli Lilly and Company. RK is an employee of IQVIA. JSS has received grant/research support, consulting fees and/or speakers’ bureau fees from AbbVie, Amgen, AstraZeneca, Astro, Bristol Myers Squibb, Celgene, Celtrion, Chugai, Eli Lilly and Company, Gilead, Glaxo, ILTOO, Janssen, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi and UCB.
Patient consent Not required.
Ethics approval The study was approved by the institutional review board or ethics committee for each centre.
Provenance and peer review Not commissioned; externally peer reviewed.
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