Effects of tofacitinib (CP-690,550), an oral janus kinase inhibitor, or adalimumab on patient reported outcomes in a phase 3 study of active rheumatoid arthritis

Background Tofacitinib (CP-690,550) is a novel, oral Janus kinase (JAK) inhibitor being investigated as a targeted immunomodulator and disease-modifying therapy for rheumatoid arthritis (RA). Objectives To compare the effects of tofacitinib 5 and 10 mg twice daily (BID), and active control adalimumab, with placebo (PBO) on patient reported outcomes (PROs) in patients (pts) with active RA and an inadequate response to methotrexate (MTX). Methods Pts in this 12-month (Mo), phase 3, randomised control trial (RCT) with RA (≥6 TJC/SJC; ESR >28 mm/h or CRP >7 mg/L) and prior MTX failure were randomised (4:4:4:1:1) to 5 treatment sequences: tofacitinib 5 mg or 10 mg BID; adalimumab 40 mg subcutaneous (SC) injections once every two weeks (Q2W); PBO advanced to tofacitinib 5 mg BID; and PBO advanced to tofacitinib 10 mg BID, all with MTX. Pts on PBO with <20% improvement in TJC and SJC after 3 months were blindly advanced to tofacitinib 5 or 10 mg BID at that time, and all other PBO pts after 6 months. We analysed changes from Baseline to Mo 6 based on the Full Analysis Set (all pts who received ≥1 dose of study drug) using a mixed-effect longitudinal model for the following PROs (secondary endpoints): PtGA [VAS]; pain (VAS); physical function (HAQ-DI); HR-QoL (SF-36); fatigue (FACIT-F), and sleep (MOS Sleep Scale). Results At Mo 6, treatment with tofacitinib 5 and 10 mg BID, and adalimumab 40 mg Q2W, resulted in statistically significant improvements from baseline vs placebo in all PROs (see Table): (Table presented) Conclusions In this phase 3 RCT in pts with RA with incomplete responses to MTX, the efficacy of tofacitinib 5 or 10 mg BID in improving PROs was significantly superior to placebo and numerically similar to adalimumab.