Tofacitinib (CP‐690,550) in patients with rheumatoid arthritis receiving methotrexate: Twelve‐month data from a twenty‐four–month phase III randomized radiographic study

Abstract Objective The purpose of this 24‐month phase III study was to examine structural preservation with tofacitinib in patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX). Data from a planned 12‐month interim analysis are reported. Methods In this double‐blind, parallel‐group, placebo‐controlled study, patients receiving background MTX were randomized 4:4:1:1 to tofacitinib at 5 mg twice daily, tofacitinib at 10 mg twice daily, placebo to tofacitinib at 5 mg twice daily, and placebo to tofacitinib at 10 mg twice daily. At month 3, nonresponder placebo‐treated patients were advanced in a blinded manner to receive tofacitinib as indicated above; remaining placebo‐treated patients were advanced at 6 months. Four primary efficacy end points were all analyzed in a step‐down procedure. Results At month 6, response rates according to the American College of Rheumatology 20% improvement criteria for tofacitinib at 5 mg and 10 mg twice daily were higher than those for placebo (51.5% and 61.8%, respectively, versus 25.3%; both P < 0.0001). At month 6, least squares mean (LSM) changes in total modified Sharp/van der Heijde score for tofacitinib at 5 mg and 10 mg twice daily were 0.12 and 0.06, respectively, versus 0.47 for placebo ( P = 0.0792 and P ≤ 0.05, respectively). At month 3, LSM changes in the Health Assessment Questionnaire disability index score for tofacitinib at 5 mg and 10 mg twice daily were –0.40 (significance not declared due to step‐down procedure) and –0.54 ( P < 0.0001), respectively, versus –0.15 for placebo. At month 6, rates of remission (defined as a value <2.6 for the 4‐variable Disease Activity Score in 28 joints using the erythrocyte sedimentation rate) for tofacitinib at 5 mg and 10 mg twice daily were 7.2% (significance not declared due to step‐down procedure) and 16.0% ( P < 0.0001), respectively, versus 1.6% for placebo. The safety profile was consistent with findings in previous studies. Conclusion Data from this 12‐month interim analysis demonstrate that tofacitinib inhibits progression of structural damage and improves disease activity in patients with RA who are receiving MTX.