Arthritis Rheumatol DOI 10.1002/art.40054. Accepted article.In this Phase 2b study in patients with moderate to severe RA, once-daily peficitinib in combination with limited csDMARDs reduced the symptoms of RA, demonstrated adose-dependent ACR20 response rate over 12 weeks, and showed acceptable tolerability. This 12-week study included patients who had an inadequate response or intolerance to csDMARDs (N=289). Patients were randomised 1:1:1:1:1 to peficitinib 25-, 50-, 100, 150 mg or matching placebo. Statistically significant differences in the ACR20 response rate versus placebo at Week 12 (primary endpoint) were reported with peficitinib 100- and 150 mg; response was rapid, with significance reached by Week 2. Patients receiving these higher doses of peficitinib also achieved a statistically significant decrease in DAS28(ESR) and DAS28(CRP) from baseline at Week 4, which was maintained to Week 12.Overall, the incidence of AEs was similar between patients receiving peficitinib and placebo, the most common being upper respiratory infection, nausea and urinary tract infection.Although not a monotherapy study, the current study allowed assessment of the safety and efficacy of peficitinib in the setting of no MTX use. Longer-term and larger-scale Phase 3 studies are currently ongoing using the peficitinib 100- and 150 mg doses.