Tofacitinib withdrawal and retreatment in moderate-to-severe chronic plaque psoriasis: a randomized controlled trial

Background Tofacitinib is an oral Janus kinase inhibitor being investigated for the treatment of moderate-to-severe plaque psoriasis. Objectives To compare outcomes following tofacitinib withdrawal with outcomes of continuation. Methods In this phase 3 study (NCT01186744), patients received tofacitinib 5 mg (n = 331) or 10 mg (n = 335) twice daily for 24 weeks. The patients who achieved both >= 75% reduction in Psoriasis Area and Severity Index (PASI 75) score from baseline and Physician's Global Assessment (PGA) of 'clear' or 'almost clear' (PGA response) received a placebo (withdrawal) or the previous dose. At relapse (> 50% reduction in the PASI improvement during initial treatment) or week 40, the patients received the initial dose. Results Initial treatment: 33.5% and 55.2% achieved both PASI 75 and PGA responses with tofacitinib 5 and 10 mg twice daily, respectively, making them eligible for the treatment-withdrawal period. Withdrawal: 56.2%, 62.3%, 23.3% and 26.1% maintained PASI 75 responses with tofacitinib 5, 10 mg, placebo (5 mg) and placebo (10 mg) twice daily, respectively; 49.9%, 63.9%, 22.9% and 18.0% maintained PGA responses; and 92.3%, 93.0%, 32.8% and 42.9% did not relapse. Elevations in low-density lipoprotein-cholesterol levels following initial treatment (mean increase: 8.71 mg dL(-1) with 5 mg twice daily, 10.26 mg dL(-1) with 10 mg twice daily) were reversed upon withdrawal. Retreatment: 36.8% and 61.0% of patients who relapsed achieved PASI 75 responses with tofacitinib 5 or 10 mg after 16 weeks; 44.8% and 57.1% regained PGA responses. Conclusions Patients who received continuous treatment maintained a response more effectively when compared with placebo recipients. Safety profiles were comparable in both the continuous treatment group and retreatment group. Of those patients who relapsed, up to 60% recaptured a response with tofacitinib.