Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: a phase 3 randomised non-inferiority trial

Summary Background New therapeutic options are needed for patients with psoriasis. Tofacitinib, an oral Janus kinase inhibitor, is being investigated as a treatment for moderate-to-severe chronic plaque psoriasis. In this study, we aimed to compare two tofacitinibdoses with high-dose etanerceptor placebo in this patient population. Methods In this phase 3, randomised, multicentre, double-dummy, placebo-controlled, 12-week, non-inferiority trial, adult patients with chronic stable plaque psoriasis (for ≥12 months) who were candidates for systemic or phototherapy and had a Psoriasis Areaand Severity Index(PASI) score of 12 or higher and a Physician's Global Assessment (PGA) of moderate or severe, and had failed to respond to, had a contraindication to, or were intolerant to at least one conventional systemic therapy, were enrolled from 122 investigational dermatology centres worldwide. Eligible patients were randomly assigned in a 3:3:3:1 ratio to receive tofacitinib5 mg or 10 mg twice daily at about 12 h intervals, etanercept50 mg subcutaneously twice weekly at about 3–4 day intervals, or placebo. Randomisation was done by a computer-generated randomisation schedule, and all patients and study personnel were masked to treatment assignment. The co-primary endpoints were the proportion of patients at week 12 with at least a 75% reduction in the PASI score from baseline (PASI75 response) and the proportion of patients achieving a PGA score of "clear" or "almost clear" (PGA response), analysed in the full analysis set (all patients who were randomised and received at least one dose of study drug). This study is registered with ClinicalTrials.gov, number NCT01241591. Findings Between Nov 29, 2010, and Sept 13, 2012, we enrolled 1106 eligible adult patients with chronic plaque psoriasis and randomly assigned them to the four treatment groups (330 to tofacitinib5 mg twice daily, 332 to tofacitinib10 mg twice daily, 336 to etanercept50 mg twice weekly, and 108 to placebo). Of these patients, 1101 actually received their assigned study medication (329 in the tofactinib 5 mg group, 330 in the tofacitinib10 mg group, 335 in the etanerceptgroup, and 107 in the placebo group). At week 12, PASI75 responses were recorded in 130 (39·5%) of 329 patients in the tofacitinib5 mg group, 210 (63·6%) of 330 in the tofacitinib10 mg group, 197 (58·8%) of 335 in the etanerceptgroup, and six (5·6%) of 107 in the placebo group. A PGA response was achieved by 155 (47·1%) of 329 patients in the tofacitinib5 mg group, 225 (68·2%) of 330 in the tofacitinib10 mg group, 222 (66·3%) of 335 in the etanerceptgroup, and 16 (15·0%) of 107 in the placebo group. The rate of adverse events was similar across the four groups, with serious adverse events occurring in seven (2%) of 329 patients in the tofacitinib5 mg group, five (2%) of 330 in the tofacitinib10 mg group, seven (2%) of 335 in the etanerceptgroup, and two (2%) of 107 in the placebo group. Three (1%) of 329 patients in the tofacitinib5 mg group, ten (3%) of 330 in the tofacitinib10 mg group, 11 (3%) of 335 in the etanerceptgroup, and four (4%) of 107 patients in the placebo group discontinued their assigned treatment because of adverse events. Intepretation In patients with moderate-to-severe plaque psoriasis, the 10 mg twice daily dose of tofacitinibwas non-inferior to etanercept50 mg twice weekly and was superior to placebo, but the 5 mg twice daily dose did not show non-inferiority to etanercept50 mg twice weekly. The adverse event rates over 12 weeks were similar for tofacitiniband etanercept. This study indicates that in the future tofacitinibcould provide a convenient and well-tolerated therapeutic option for patients with moderate-to-severe plaque psoriasis. Funding Pfizer Inc.