Secukinumab for patients failing previous tumour necrosis factor-α inhibitor therapy: results of a randomized open-label study (SIGNATURE)

Background Efficacy data on therapies for patients with psoriasis who have failed tumour necrosis factor (TNF)-alpha inhibitor therapy is limited. Objectives To determine the effectiveness and tolerability of secukinumab, an interleukin (IL)-17A inhibitor, in patients with moderate/severe chronic plaque psoriasis with documented efficacy failure of TNF-alpha inhibitor therapy (SIGNATURE study). Methods This was a randomized, open-label, noncomparator study in 53 dermatology centres in the U.K. and Republic of Ireland. Patients were randomized 1 : 1 to receive secukinumab 300 mg or 150 mg subcutaneously every week for 4 weeks, then 4-weekly thereafter. Patients were stratified by their prior efficacy failure with TNF-alpha inhibitors. Only patients who started and stayed on the same dose at each time point were included for efficacy assessments. Results In total, 233 patients were analysed. The primary end point was met, with a statistically significant improvement in response rates [75% reduction in Psoriasis Area and Severity Index (PASI 75)] from baseline to week 16 in both secukinumab 300 mg and 150 mg dose groups [77 of 118 patients (65.3%) and 51 of 115 patients (44.3%), respectively; P < 0.0001]. After 72 weeks, in patients starting and remaining on 300 mg, 77% (54 of 70) achieved PASI 75. Improvements in Dermatology Life Quality Index from baseline to week 16 occurred and were maintained up to 72 weeks. The safety profile was generally consistent with previous secukinumab studies, although a higher incidence of some adverse events (e.g. candida infections) was observed. Conclusions This study provides evidence of efficacy and safety of secukinumab for treatment of patients with psoriasis who failed prior TNF-alpha inhibitor therapy. This study represents a 'real-world' population, providing reassurance that secukinumab is a treatment option in this difficult-to-treat population.