Tofacitinib or Adalimumab versus Placebo for Psoriatic Arthritis.

N Engl J Med

From the Swedish Medical Center and University of Washington, Seattle (P.M.); Cabrini Health and Monash University, Melbourne, VIC, Australia (S.H.); the Department of Rheumatology, St. Vincent's University Hospital and Conway Institute of Biomolecular and Biomedical Research, University College, Dublin (O.F.); Leiden University Medical Center, Leiden, the Netherlands (D.H.); Brigham and Women's Hospital, Harvard Medical School, Boston (J.F.M.); Centro Multidisciplinario para el Desarrollo Especializado de la Investigación Clínica en Yucatán Sociedad Civil Privada, Merida, Mexico (F.A.-Z.); the Department of Rheumatology and Clinical Immunology, Medical University of Poznan, Poznan, Poland (D.C.); Pfizer, Groton, CT (D.G., C.W., S.M., K.S.K.); and Pfizer, Collegeville, PA (T.H.).

Published: October 2017

AI Article Synopsis

  • Tofacitinib is an oral Janus kinase inhibitor being studied for psoriatic arthritis in patients who didn't respond well to standard treatments.
  • The study was a 12-month, phase 3 trial that compared two doses of tofacitinib (5 mg and 10 mg), adalimumab, and placebo in a randomized setup involving over 370 patients.
  • At the 3-month mark, the 10 mg tofacitinib group showed a significant improvement in response rates and disability scores compared to placebo, demonstrating its effectiveness for treating active psoriatic arthritis.

Article Abstract

Background: Tofacitinib is an oral Janus kinase inhibitor that is under investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib in patients with active psoriatic arthritis who previously had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (DMARDs).

Methods: In this 12-month, double-blind, active-controlled and placebo-controlled, phase 3 trial, we randomly assigned patients in a 2:2:2:1:1 ratio to receive one of the following regimens: tofacitinib at a 5-mg dose taken orally twice daily (107 patients), tofacitinib at a 10-mg dose taken orally twice daily (104), adalimumab at a 40-mg dose administered subcutaneously once every 2 weeks (106), placebo with a blinded switch to the 5-mg tofacitinib dose at 3 months (52), or placebo with a blinded switch to the 10-mg tofacitinib dose at 3 months (53). Placebo groups were pooled for analyses up to month 3. Primary end points were the proportion of patients who had an American College of Rheumatology 20 (ACR20) response (≥20% improvement from baseline in the number of tender and swollen joints and at least three of five other important domains) at month 3 and the change from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) score (scores range from 0 to 3, with higher scores indicating greater disability) at month 3.

Results: ACR20 response rates at month 3 were 50% in the 5-mg tofacitinib group and 61% in the 10-mg tofacitinib group, as compared with 33% in the placebo group (P=0.01 for the comparison of the 5-mg dose with placebo; P<0.001 for the comparison of the 10-mg dose with placebo); the rate was 52% in the adalimumab group. The mean change in the HAQ-DI score was -0.35 in the 5-mg tofacitinib group and -0.40 in the 10-mg tofacitinib group, as compared with -0.18 in the placebo group (P=0.006 for the comparison of the 5-mg dose with placebo; P<0.001 for the comparison of the 10-mg dose with placebo); the score change was -0.38 in the adalimumab group. The rate of adverse events through month 12 was 66% in the 5-mg tofacitinib group, 71% in the 10-mg tofacitinib group, 72% in the adalimumab group, 69% in the placebo group that switched to the 5-mg tofacitinib dose, and 64% in the placebo group that switched to the 10-mg tofacitinib dose. There were four cases of cancer, three serious infections, and four cases of herpes zoster in patients who received tofacitinib during the trial.

Conclusions: The efficacy of tofacitinib was superior to that of placebo at month 3 in patients with psoriatic arthritis who had previously had an inadequate response to conventional synthetic DMARDs. Adverse events were more frequent with tofacitinib than with placebo. (Funded by Pfizer; OPAL Broaden ClinicalTrials.gov number, NCT01877668 .).

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http://dx.doi.org/10.1056/NEJMoa1615975DOI Listing

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