Patient-reported outcomes for tofacitinib with and without methotrexate, or adalimumab with methotrexate, in rheumatoid arthritis: a phase IIIB/IV trial

RMD Open. 2019 Oct 1;5(2):e001040. doi: 10.1136/rmdopen-2019-001040. eCollection 2019.

Abstract

Objective: To provide the first direct comparison of patient-reported outcomes (PROs) following treatment with tofacitinib monotherapy versus tofacitinib or adalimumab (ADA) in combination with methotrexate (MTX) in patients with rheumatoid arthritis (RA) with inadequate response to MTX (MTX-IR).

Methods: ORAL Strategy (NCT02187055), a phase IIIB/IV, head-to-head, randomised controlled trial, assessed non-inferiority between tofacitinib 5 mg two times per day monotherapy, tofacitinib 5 mg two times per day+MTX and ADA 40 mg every other week+MTX. PROs assessed included the following: Patient Global Assessment of disease activity (PtGA), Pain, Health Assessment Questionnaire-Disability Index, Functional Assessment of Chronic Illness Therapy-Fatigue and 36-Item Short-Form Health Survey (SF-36) summary and domain scores.

Results: Substantial improvements from baseline were reported across all PROs in all treatment arms, which, in the majority, met or exceeded minimum clinically important differences. Compared with tofacitinib monotherapy, tofacitinib+MTX combination treatment conferred significantly greater improvements in PtGA, Pain and SF-36 physical component summary scores at month 6. Statistically or numerically greater improvements were often, but not uniformly, reported for combination treatments compared with tofacitinib monotherapy at other time points.

Conclusion: Treatment with tofacitinib+MTX, ADA+MTX and tofacitinib monotherapy resulted in clinically meaningful improvements in PROs in MTX-IR patients with RA. These were comparatively greater with combination treatments versus tofacitinib monotherapy, although differences between treatment arms were small, limiting our ability to confer clinical meaning.

Trial registration number: NCT02187055.

Keywords: DMARDs (biologic); DMARDs (synthetic); outcomes research; rheumatoid arthritis.

Publication types

  • Clinical Trial, Phase III
  • Clinical Trial, Phase IV
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab / administration & dosage
  • Adalimumab / therapeutic use*
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / drug therapy*
  • Drug Therapy, Combination
  • Humans
  • Methotrexate / administration & dosage
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Piperidines / administration & dosage
  • Piperidines / therapeutic use*
  • Pyrimidines / administration & dosage
  • Pyrimidines / therapeutic use*
  • Pyrroles / administration & dosage
  • Pyrroles / therapeutic use*
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Piperidines
  • Pyrimidines
  • Pyrroles
  • tofacitinib
  • Adalimumab
  • Methotrexate

Associated data

  • ClinicalTrials.gov/NCT02187055