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Management


secukinumab on weeks 0–4 and then once every four weeks for a period of 52 weeks. FIXTURE also included a sc etanercept arm, and patients received 50mg twice-weekly for 12 weeks and then once-weekly for a total of 52 weeks.2 There was an option for patients in ERASURE, FIXTURE, FEATURE and JUNCTURE to enter long-term extension studies at the end of the initial study. The co-primary endpoints for the trials were the proportion of patients who achieved a PASI75 response (that is, a 75% reduction in the baseline Psoriasis Area and Severity Index score) and the proportion of patients who achieved a Modified 2011 Investigator’s Global Assessment (IGAmod2011) score of 0 or 1 and an improvement from baseline of >2 at 12 weeks.2–4


ERASURE and FIXTURE


A total of 738 patients (in the ERASURE study) and 1306 patients (in the FIXTURE study) were randomised to sc secukinumab at a dose of 300mg or 150mg, placebo, or (in the FIXTURE study only) etanercept at a dose of 50mg (administered twice weekly for 12 weeks, then once weekly).2


The proportion of patients who met the criterion for PASI75 at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 81.6% with 300mg secukinumab and 4.5% with placebo. In the FIXTURE study, the rates were 77.1% with 300mg secukinumab, 44% with etanercept, and 4.9% with placebo (p<0.001 for each secukinumab dose versus comparators). The proportion of patients with a response of 0 or 1 on the IGAmod2011 at week 12 was higher with each secukinumab dose than with placebo or etanercept. In ERASURE, the rates were 65.3% with 300mg and 2.4% with placebo; in the FIXTURE study, the rates were 62.5% with 300mg secukinumab, 27.2% with etanercept, and 2.8% with placebo (p<0.001 for each secukinumab dose versus comparators). The rates of infection were numerically higher with secukinumab than with placebo in both studies and were similar to those with etanercept.2


FEATURE 24


Subjects were randomised 1:1:1 to secukinumab 300 or 150mg or placebo. Treatments were delivered using a prefilled syringe once weekly to week 4, and again at week 8. Co-primary


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endpoints were secukinumab superiority over placebo for week 12 PASI75 and IGAmod2011 0/1 response rates. Secondary endpoints included prefilled syringe usability, determined by observer rating of successful, hazard-free self- injection and subject rating of acceptability by the Self-Injection Assessment Questionnaire (SIAQ).3 Co-primary endpoints were met, with demonstration of superiority for each secukinumab dose versus placebo at week 12 (PASI75: 75·9% and 0% for secukinumab 300mg and placebo; IGAmod2011 0/1: 69·0% and 0%, respectively; p<0.0001). Usability was high and 100% of subjects successfully self-administered treatment at week 1. Subjects reported high acceptability of the syringe throughout the trial (assessed by the SIAQ). No new/unexpected safety issues were observed.3


Secukinumab administration by this method was reliable, effective and convenient, with an acceptable safety profile and high usability.


JUNCTURE


Secukinumab delivery via an autoinjector/pen was investigated. Subjects with moderate to severe plaque psoriasis were randomised to secukinumab 300mg, 150mg or placebo self-injection once weekly to week 4, then every four weeks. Co-primary endpoints at week 12 were PASI 75 and clear/almost clear skin by IGmod2011 0/1. Secondary endpoints included autoinjector usability, assessed by successful, hazard-free self-injection and subject-reported acceptability on the SIAQ.4


Week 12 PASI75 and IGAmod2011 0/1 responses were superior with secukinumab 300mg (86.7% and 73.3%, respectively) versus placebo (3.3% and 0%, respectively; p<0.0001 for all). All subjects successfully self-administered treatment at week 1, without critical use-related hazards. Subject acceptability of autoinjector was high throughout the trial period. Adverse events were higher with secukinumab (300mg, 70.0%) versus placebo (54.1%) (mainly mild/moderate nasopharyngitis).4


Phase IIIb trials


Additional randomised, double-blind, multicentre, Phase IIIb trials have been completed, or are ongoing, as detailed below.


CLEAR CLEAR was a 52-week, double-blind


study directly comparing secukinumab with ustekinumab.5


A total of 676 subjects


were randomised 1:1 to subcutaneous injection of secukinumab 300mg or ustekinumab. The primary endpoint was PASI90 response at week 16.5


Secukinumab (79.0%) was superior to ustekinumab (57.6%; p<0.0001). The PASI100 score at week 16 was also significantly greater with secukinumab (44.3%) than ustekinumab (28.4%; p<0.0001). PASI75 score at week 4 was superior for secukinumab (50.0%) versus ustekinumab (20.6%; p<0.0001). Percentage of subjects with the Dermatology Life Quality Index (DLQI) score 0/1 was significantly higher with secukinumab (71.9%) than ustekinumab (57.4%; p<0.0001). The safety profile of secukinumab was comparable to ustekinumab.5


GESTURE and TRANSFIGURE GESTURE and TRANSFIGURE investigated the efficacy of sc secukinumab 150 or 300mg versus placebo in patients with moderate to severe palmoplantar psoriasis (n=205), or moderate to severe psoriasis with major nail involvement (n=198), respectively.6,7 Secukinumab was significantly more effective than placebo.


In the GESTURE study, a ppIGA 0 or 1 response was achieved at week 16 (primary endpoint) by 33.3% (300mg) versus 1.5%, respectively (p<0.001).6


The


change from baseline in palmoplantar Psoriasis Area and Severity Index (ppPASI) score was –54.6% (300mg) versus –4.1% (placebo), respectively (p<0.001).6


In TRANSFIGURE, the change from baseline in Nail Psoriasis Severity Index (NAPSI) score at week 16 (primary endpoint) was–45.3 versus –10.8% (p<0.0001) in secukinumab 300mg versus placebo group.7


PASI75 response


rates and PASI90 response rates were also significantly higher in those patients receiving secukinumab.7


Extension data


In an extension of the FIXTURE and ERASURE studies, 995 patients who were PASI75 responders at week 52 received either 300mg, 150mg or placebo for an additional year (week 104).8


After two full


years of therapy, seven out of ten (71%) patients treated with 300mg had clear or almost clear skin (PASI90); four out of ten (44%) had clear skin (PASI100) and almost nine out of ten (88%) patients


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