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Original article
Patient-reported outcomes for tofacitinib with and without methotrexate, or adalimumab with methotrexate, in rheumatoid arthritis: a phase IIIB/IV trial
  1. Vibeke Strand1,
  2. Eduardo Mysler2,
  3. Robert J Moots3,
  4. Gene V Wallenstein4,
  5. Ryan DeMasi5,
  6. David Gruben4,
  7. Koshika Soma4,
  8. Noriko Iikuni6,
  9. Josef S Smolen7 and
  10. Roy Fleischmann8
  1. 1 Division of Immunology/Rheumatology, Stanford University, Palo Alto, California, USA
  2. 2 Reumatólogo en Organización Médica de Investigación, Buenos Aires, Argentina
  3. 3 Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK
  4. 4 Pfizer Inc, Groton, Connecticut, USA
  5. 5 Pfizer Inc, Collegeville, Pennsylvania, USA
  6. 6 Pfizer Inc, New York, New York, USA
  7. 7 Division of Rheumatology, Medical University of Vienna, Vienna, Austria
  8. 8 Rheumatology Division, Metroplex Clinical Research Center and University of Texas Southwestern Medical Center, Dallas, Texas, USA
  1. Correspondence to Dr Gene V Wallenstein; genewallenstein{at}


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.

  • DMARDs (biologic)
  • DMARDs (synthetic)
  • outcomes research
  • rheumatoid arthritis

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  • Contributors RF, EM, VS and RJM were involved in the conception, design and analyses of the study. DG performed the data and statistical analyses. RF and EM were involved in patient recruitment, study monitoring and/or data acquisition (conducted the experiment). All authors were involved in data interpretation and manuscript drafting, reviewing and development. The views and opinions expressed within this manuscript are those of all authors and do not necessarily represent those of the sponsor.

  • Funding This work was supported by Pfizer Inc.

  • Competing interests VS has received consulting fees from AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Corrona, Eli Lilly, Genentech/Roche, GSK, Janssen, Merck, Novartis, Pfizer Inc, Regeneron, Samsung, Sandoz, Sanofi and UCB. EM has received research grants, consulting fees or other remuneration from, and is a member of the speakers’ bureau for, AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, MedImmune, Pfizer Inc and Roche. RJM has received research grants and consulting fees from, or is a member of the speakers’ bureau for, AbbVie, AKL Pharma, Biogen, Bristol-Myers Squibb, Chugai, Eli Lilly, Novartis, Pfizer Inc, Roche, Sandoz, Sanofi and UCB. DG, KS and NI are employees and shareholders of Pfizer Inc. GVW and RD were employees and shareholders of Pfizer Inc at the time of the analysis. JSS has received consulting fees, speaking fees and honoraria from AbbVie, Amgen, AstraZeneca, Astro, Celgene, Celltrion, Eli Lilly, GSK, ILTOO, Janssen, MedImmune, MSD, Novartis-Sandoz, Pfizer Inc, Roche, Samsung, Sanofi and UCB Pharma; and has received institutional grants from AbbVie, Eli Lilly, Janssen, MSD, Pfizer Inc and Roche. RF has received research grants or consulting fees from AbbVie, ACEA, Amgen, AstraZeneca, Bristol-Myers Squibb, Celltrion, Eli Lilly, Genentech, GSK, Janssen, Novartis, Pfizer Inc, Samsung, Sanofi-Aventis, Tahio and UCB.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Upon request, and subject to certain criteria, conditions and exceptions (see https :// for more information), Pfizer will provide access to individual deidentified participant data from Pfizer-sponsored global interventional clinical studies conducted for medicines, vaccines and medical devices (1) for indications that have been approved in the US and/or EU or (2) in programmes that have been terminated (ie, development for all indications has been discontinued). Pfizer will also consider requests for the protocol, data dictionary and statistical analysis plan. Data may be requested from Pfizer trials 24 months after study completion. The deidentified participant data will be made available to researchers whose proposals meet the research criteria and other conditions, and for which an exception does not apply, via a secure portal. To gain access, data requestors must enter into a data access agreement with Pfizer.

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