Abstract
Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This post hoc analysis investigated the effect of methotrexate (MTX) dose on the efficacy of tofacitinib in patients with RA. ORAL Scan (NCT00847613) was a 2-year, randomized, Phase 3 trial evaluating tofacitinib in MTX-inadequate responder (IR) patients with RA. Patients received tofacitinib 5 or 10 mg twice daily (BID), or placebo, with low (≤12.5 mg/week), moderate (>12.5 to <17.5 mg/week), or high (≥17.5 mg/week) stable background MTX. Efficacy endpoints (at months 3 and 6) included American College of Rheumatology (ACR) 20/50/70 response rates, and mean change from baseline in Clinical Disease Activity Index (CDAI), Disease Activity Score in 28 joints (DAS28)–4(erythrocyte sedimentation rate [ESR]), Health Assessment Questionnaire-Disability Index (HAQ-DI), and modified Total Sharp score. 797 patients were treated with tofacitinib 5 mg BID (N = 321), tofacitinib 10 mg BID (N = 316), or placebo (N = 160); 242, 333, and 222 patients received low, moderate, and high MTX doses, respectively. At months 3 and 6, ACR20/50/70 response rates were greater for both tofacitinib doses vs placebo across all MTX doses. At month 3, mean changes from baseline in CDAI and HAQ-DI were significantly greater for both tofacitinib doses vs placebo, irrespective of MTX category; improvements were maintained at month 6. Both tofacitinib doses demonstrated improvements in DAS28–4(ESR), and less structural progression vs placebo, across MTX doses at month 6. Tofacitinib plus MTX showed greater clinical and radiographic efficacy than placebo in MTX-IR patients with RA, regardless of MTX dose.
Highlights
Current guidelines advise that treatment of rheumatoid arthritis (RA) should be initiated with conventional synthetic disease-modifying antirheumatic drugs, such as methotrexate (MTX)
A total of 797 patients were randomized to receive tofacitinib 5 mg BID (N = 321), tofacitinib 10 mg BID (N = 316), or placebo (N = 160), all in combination with background MTX; patients continued to receive concomitant MTX at the dose they were receiving at study start
BMI, proportion of Caucasian patients, GC use, swollen and tender joint counts, and Clinical Disease Activity Index (CDAI) scores tended to be higher among patients in the high MTX dose category, and proportion of patients with prior tumor necrosis factor inhibitors (TNFi) therapy, which tended to be higher in the low MTX dose category (Table 1)
Summary
Current guidelines advise that treatment of rheumatoid arthritis (RA) should be initiated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), such as methotrexate (MTX). Intervention with csDMARDs, usually MTX, has been shown to be beneficial in achieving a good clinical response in a proportion of patients, with resulting modification of the course of the disease [1, 3, 4]. There is extensive evidence to suggest that concomitant use of a bDMARD with MTX is beneficial in achieving treatment goals [5,6,7,8,9,10,11,12]. It is not clear whether there is a minimum or maximum dose
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