3 years ago

Tofacitinib or Adalimumab versus Placebo for Psoriatic Arthritis

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.)

Supported by Pfizer.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

We thank the patients, investigators, and trial teams; and Alice MacLachlan, Ph.D., of Complete Medical Communications, for medical writing support with an earlier version of the manuscript.

Source Information

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.).

Address reprint requests to Dr. Mease at Seattle Rheumatology Associates, 601 Broadway, Suite 600, Seattle, WA 98122, or at .

A complete list o

-Abstract Truncated-

Publisher URL: http://www.nejm.org/doi/full/10.1056/NEJMoa1615975

DOI: 10.1056/NEJMoa1615975

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