SAT0256 Tofacitinib with and without methotrexate versus adalimumab with methotrexate for the treatment of rheumatoid arthritis: patient-reported outcomes from a phase 3b/4 randomised trial
Authors: V. Strand, E. Mysler, R.J. Moots, G. Wallenstein, R. DeMasi, D. Gruben, K. Soma, N. Iikuni, R. Fleischmann
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). <h3>Objectives</h3> To compare patient-reported outcomes (PROs) among patients receiving tofacitinib monotherapy, tofacitinib +methotrexate (MTX) and adalimumab (ADA) +MTX, in a head-to-head trial of patients with RA and inadequate responses to MTX (MTX-IR). <h3>Methods</h3> ORAL Strategy (NCT02187055) was a Phase 3b/4, 1 year, triple dummy, active randomised controlled trial (RCT). Patients were randomised 1:1:1 to receive tofacitinib 5 mg twice daily (BID; tofa mono), tofacitinib 5 mg BID+MTX (tofa +MTX) or subcutaneous ADA 40 mg every other week +MTX (ADA +MTX); MTX doses were 15–25 mg/wk. PROs (secondary endpoints in this RCT) assessed at Months (Mos) 6 and 12 included mean changes from baseline in: patient global assessment of disease activity (visual analogue scale [VAS]); arthritis pain (VAS); Health Assessment Questionnaire-Disability Index (HAQ-DI); Short Form-36 Health Survey; EuroQol 5-dimensions Questionnaire; Work Productivity and Activity Impairment Questionnaire; Functional Assessment of Chronic Illness Therapy-Fatigue; and the proportion of patients reporting improvements in HAQ-DI ≥minimum clinically important difference (MCID; −0.22). Nominal p values were calculated with no adjustment for multiple comparisons. <h3>Results</h3> Among 1146 patients treated (tofa mono: n=384; tofa +MTX: n=376; ADA+MTX: n=386), baseline demographics and disease characteristics were comparable. At Mos 6 and 12, improvements in all PROs were similar for tofa +MTX and ADA+MTX (there were essentially no differences based on nominal p values) and numerically greater than with tofa mono (Table). Mean changes from baseline in HAQ-DI scores were similar in each treatment group at Mos 6 and 12; similar proportions reported improvements≥MCID. <h3>Conclusions</h3> MTX-IR patients with RA reported PRO improvements with all 3 treatment regimens that were clinically meaningful, comparable for tofacitinib +MTX and adalimumab +MTX and numerically higher with combination therapy than with tofa mono. Nominal p values should be interpreted with caution as they were not controlled for Type 1 error. <h3>Acknowledgements</h3> Study sponsored by Pfizer Inc. Medical writing support was provided by D Binks of CMC and funded by Pfizer Inc. <h3>Disclosure of Interest</h3> V. Strand Consultant for: AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Corrona, Eli Lilly, Janssen, Merck, Novartis, Pfizer Inc, Regeneron, Samsung, Sanofi, and UCB, E. Mysler Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lily, Janssen, MedImmune, Pfizer Inc, and Roche, Consultant for: AbbVie, Bristol-Myers Squibb, Eli Lily, Janssen, MedImmune, Pfizer Inc, and Roche, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lily, Janssen, MedImmune, Pfizer Inc, and Roche, R. Moots Grant/research support from: Biogen, Bristol-Myers Squibb, Chugai, Novartis, Pfizer Inc, Roche, Sandoz, and UCB, Consultant for: Biogen, Bristol-Myers Squibb, Chugai, Novartis, Pfizer Inc, Roche, Sandoz, and UCB, Speakers bureau: Biogen, Bristol-Myers Squibb, Chugai, Novartis, Pfizer Inc, Roche, Sandoz, and UCB, G. Wallenstein Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, R. DeMasi Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, D. Gruben Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, K. Soma Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, N. Iikuni Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, R. Fleischmann Grant/research support from: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celltrion, Genentech, GSK, Janssen, Lilly, Novartis, Pfizer Inc, Sanofi-Aventis, and UCB, Consultant for: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celltrion, Genentech, GSK, Janssen, Lilly, Novartis, Pfizer Inc, Sanofi-Aventis, and UCB