title: Efficacy of tofacitinib in patients with rheumatoid arthritis stratified by background methotrexate dose group.
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.
authors.affiliation: Metroplex Clinical Research Center and University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: R
authors.initials: R
authors.lastname: Fleischmann
authors.affiliation: Swedish Medical Center and University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Mease
authors.affiliation: Hospital for Special Surgery, New York, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Schwartzman
authors.affiliation: Pfizer Inc, New York, NY, USA.
authors.forename: L-J
authors.initials: LJ
authors.lastname: Hwang
authors.affiliation: Pfizer Inc, Groton, CT, USA.
authors.forename: K
authors.initials: K
authors.lastname: Soma
authors.affiliation: Pfizer Inc, Groton, CT, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Connell
authors.affiliation: Pfizer Inc, Collegeville, PA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Takiya
authors.affiliation: Pfizer Inc, Collegeville, PA, USA. stratis.bananis@pfizer.com.
authors.forename: E
authors.initials: E
authors.lastname: Bananis
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy*; D001799:Blood Sedimentation; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D011758:Pyrroles / Q000008:administration & dosage*; D012044:Regression Analysis; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D053612:Janus Kinases; D008727:Methotrexate
keywords: Disease activity; Janus kinase; Methotrexate; Radiographic progression; Rheumatoid arthritis; Tofacitinib