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

Summary 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. What's already known about this topic? Tofacitinib inhibits Janus kinase (JAK)1/JAK3 implicated in psoriasis pathogenesis. Oral tofacitinib was effective in treating psoriasis in a phase 2b study. Patients may need to stop treatment temporarily. What does this study add? Continuous tofacitinib treatment was most effective in psoriasis, but if treatment had been interrupted, retreatment was possible. Up to 50% of patients recaptured a ≥ 75% improvement in Psoriasis Area Severity Index score upon retreatment. Tofacitinib is well tolerated. No patients experienced psoriasis rebound during treatment