SummaryBackground Some patients with plaque psoriasis experience secondary failure of tumour necrosis factor inhibitor therapy. Objectives To evaluate efficacy, safety and patient-reported outcomes (PROs) with etanercept in patients with secondary adalimumab failure. Methods This phase IV open-label single-arm estimation study (NCT01543204) enrolled patients on adalimumab who had achieved static Physician's Global Assessment (sPGA) score 0/1 (clear/almost clear). Patients subsequently lost response, defined as sPGA ≥ 3 or loss of 50% improvement in Psoriasis Area and Severity Index (PASI 50). At baseline, patients had involved body surface area ≥ 10%, sPGA ≥ 3 and PASI ≥ 10. Antiadalimumab antibodies (ADAs) were measured at screening. Patients received etanercept 50 mg twice weekly for 12 weeks, followed by 50 mg weekly. The primary end point was sPGA 0/1 at week 12 (intention-to-treat analysis; no hypothesis tested). Additional outcomes included rates of sPGA 0/1, PASI responses, safety, PROs of itch, pain and flaking, Dermatology Life Quality Index, treatment satisfaction and Work Productivity and Activity Impairment questionnaire. Results Sixty-four patients enrolled; 67% had ADAs. sPGA 0/1 rates at week 12 were 39Á7% [95% confidence interval (CI) 27Á6-52Á8; primary end point] and 45% (95% CI 29Á3-61Á5) for patients positive for ADAs and 35% (95% CI 15Á4-59Á2) for patients negative for ADAs. PASI 75 response rates at week 12 were 47Á5% (95% CI 31Á5-63Á9) for patients who were positive for ADAs and 50% (95% CI 27Á2-72Á8) for patients negative for ADAs. No new safety signals were observed. PROs of itch, pain and flaking consistently improved at week 12 and were maintained through week 24. Conclusions Patients with psoriasis who experienced secondary failure of adalimumab achieved satisfactory response to etanercept regardless of ADA status.