Secukinumab for patients failing previous TNFα-inhibitor therapy: results of a randomised open-label study (Signature).

BACKGROUND: Efficacy data on therapies for psoriasis patients who have failed tumour necrosis factor (TNF)α-inhibitor therapy is limited.

OBJECTIVES: To determine the effectiveness and tolerability of secukinumab, an IL-17A inhibitor, in patients with moderate/severe chronic plaque psoriasis with documented efficacy failure to TNFα-inhibitor therapy (SIGNATURE Study).

METHODS: Randomised, open-label, non-comparator study in 53 dermatology centres in UK and Republic of Ireland. Patients randomised 1:1 to receive secukinumab 300mg or 150mg subcutaneously weekly for 4 weeks, then 4-weekly thereafter. Patients were stratified by their prior efficacy failure with TNFα-inhibitors. Only patients who started and stayed on the same dose at each timepoint are included for efficacy assessments.

RESULTS: 233 patients were analysed. The primary endpoint was met, with a statistically significant improvement in response rates (i.e. 75% reduction in Psoriasis Area and Severity Index [PASI75]) from baseline to Week 16 in both secukinumab 300mg and 150mg dose groups (300mg: 77/118 [65.3%]; 150mg: 51/115 [44.3%], p<0.0001). After 72 weeks in patients starting and remaining on 300mg, 77.1% (54/70) achieved PASI75. Improvements in Dermatology Life Quality Index (DLQI) from baseline to Week 16 occurred and 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 psoriasis patients who failed prior TNFα-inhibitor therapy. This study represents a 'real world' population, providing reassurance that secukinumab is a treatment option in this difficult-to-treat population.