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Tofacitinib for Psoriatic Arthritis in Patients with an Inadequate Response to TNF Inhibitors

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Gladman D1, Rigby W1, Azevedo VF1, Behrens F1, Blanco R1, Kaszuba A1, Kudlacz E1, Wang C1, Menon S1, Hendrikx T1, Kanik KS1. N Engl J Med. 2017 Oct 19;377(16):1525-1536. doi: 10.1056/NEJMoa1615977.

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1 From the University of Toronto, Toronto Western Hospital, Toronto (D.G.); Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center, Lebanon, NH (W.R.); Universidade Federal do Paraná, Curitiba, Brazil (V.F.A.); Goethe University and Fraunhofer Institute for Molecular Biology and Applied Ecology Project Group Translational Medicine and Pharmacology (TMP), Frankfurt, Germany (F.B.); Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Marqués de Valdecilla, Santander, Spain (R.B.); Specjalistyczne Gabinety Lekarskie DERMED, Lodz, Poland (A.K.); Pfizer, Groton, CT (E.K., C.W., S.M., K.S.K.); and Pfizer, Collegeville, PA (T.H.).

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 had previously had an inadequate response to tumor necrosis factor (TNF) inhibitors.

METHODS: In this 6-month randomized, placebo-controlled, double-blind, phase 3 trial, we randomly assigned 395 patients, in a 2:2:1:1 ratio, to four regimens: 5 mg of tofacitinib administered orally twice daily (132 patients); 10 mg of tofacitinib twice daily (132 patients); placebo, with a switch to 5 mg of tofacitinib twice daily at 3 months (66 patients); or placebo, with a switch to 10 mg of tofacitinib twice daily at 3 months (65 patients). Data from the patients who received placebo during the first 3 months of the trial were pooled. The primary end points were the percentage of patients who had at least 20% improvement according to the criteria of the American College of Rheumatology (ACR20 response) and the change from baseline score on the Health Assessment Questionnaire-Disability Index (HAQ-DI; scores range from 0 to 3, with higher scores indicating greater disability) at the month 3 analysis.

RESULTS: At 3 months, the rates of ACR20 response were 50% with the 5-mg dose of tofacitinib and 47% with the 10-mg dose, as compared with 24% with placebo (P<0.001 for both comparisons); the corresponding mean changes from baseline in HAQ-DI score were -0.39 and -0.35, as compared with -0.14 (P<0.001 for both comparisons). Serious adverse events occurred in 4% of the patients who received the 5-mg dose of tofacitinib continuously and in 6% who received the 10-mg dose continuously. Over the course of 6 months, there were four serious infections, three herpes zoster infections, one myocardial infarction, and one ischemic stroke among the patients who received tofacitinib continuously. Elevations of aspartate and alanine aminotransferase concentrations of three or more times the upper limit of the normal range occurred in more patients who received tofacitinib continuously than in patients who received placebo followed by tofacitinib.

CONCLUSIONS: In this trial involving patients with active psoriatic arthritis who had had an inadequate response to TNF inhibitors, tofacitinib was more effective than placebo over 3 months in reducing disease activity. Adverse events were more frequent with tofacitinib than with placebo. (Funded by Pfizer; OPAL Beyond ClinicalTrials.gov number, NCT01882439 .).