Secukinumab for patients failing previous tumour necrosis factor‐α inhibitor therapy: results of a randomized open‐label study (SIGNATURE)
Authors: R.B. Warren, J.N.W.B. Barker, A.Y. Finlay, A.D. Burden, B. Kirby, Y. Armendariz, R. Williams, C. Hatchard, S. Khare, C.E.M. Griffiths
Journal: British Journal of Dermatology (2019)

Efficacy data on therapies for patients with psoriasis who have failed tumour necrosis factor (TNF)-α inhibitor therapy is limited.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-α inhibitor therapy (SIGNATURE study).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-α inhibitors. Only patients who started and stayed on the same dose at each time point were included for efficacy assessments.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.This study provides evidence of efficacy and safety of secukinumab for treatment of patients with psoriasis who failed prior TNF-α inhibitor therapy. This study represents a 'real-world' population, providing reassurance that secukinumab is a treatment option in this difficult-to-treat population. What's already known about this topic? Conventional systemic nonbiological and tumour necrosis factor (TNF)-α inhibitor therapies for plaque psoriasis have not fully met patients' needs. There is a lack of data to support the treatment pathways for patients with psoriasis who have inadequate responses to TNF-α inhibitor therapy. Secukinumab, a recombinant high-affinity fully human monoclonal anti-human interleukin-17A antibody of the IgG1/κ-class, has shown excellent safety and efficacy in the treatment of moderate-to-severe psoriasis. What does this study add? This is the first study evaluating treatment with biologics after prior efficacy failure of TNF-α inhibitor therapy as defined by the U.K. National Institute for Health and Care Excellence criteria. Secukinumab is an effective treatment in this difficult-to-treat patient population. This study provides important practical information for clinicians managing psoriasis. Adverse events were consistent with the phase III programme for secukinumab, although some adverse events, e.g. candida, were increased.