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

Warren, R.B., Barker, J.N.W.B., Finlay, A.Y., Burden, A.D., Kirby, B., Armendariz, Y., Williams, R., Hatchard, C., Khare, S. and Griffiths, C.E.M. (2020) Secukinumab for patients failing previous tumour necrosis factor‐α inhibitor therapy: results of a randomized open‐label study (SIGNATURE). British Journal of Dermatology, 183(1), pp. 60-70. (doi: 10.1111/bjd.18623) (PMID:31628677)

Abstract

Background: Efficacy data on therapies for patients with psoriasis who have failed tumour necrosis factor (TNF)‐α 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‐α 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‐α 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‐α inhibitor therapy. This study represents a ‘real‐world’ population, providing reassurance that secukinumab is a treatment option in this difficult‐to‐treat population.

• Item Type: Articles
• Additional Information: Funding information: Novartis Pharmaceuticals UK Limited.
• Keywords: Dermatology.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Burden, Professor David
• Authors: Warren, R.B., Barker, J.N.W.B., Finlay, A.Y., Burden, A.D., Kirby, B., Armendariz, Y., Williams, R., Hatchard, C., Khare, S., and Griffiths, C.E.M.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: British Journal of Dermatology
• Publisher: Wiley
• ISSN: 1365-2133
• ISSN (Online): 1365-2133
• Published Online: 25 December 2019