Efficacy and safety of secukinumab in moderate to severe palmoplantar pustular psoriasis over 148 weeks: Extension of the 2PRECISE study

Abstract

To the Editor: Palmoplantar pustular psoriasis is a debilitating inflammatory disease confined to the palms and/or soles and resistant to treatment.1Mrowietz U. Pustular eruptions of palms and soles.in: Goldsmith LA Fitzpatrick's Dermatology in General Medicine. McGraw-Hill, New York, NY2012: 252-259Google Scholar Secukinumab, a fully human monoclonal antibody selectively targeting interleukin 17A, is efficacious in the treatment of moderate to severe psoriasis, with a sustained effect and favorable safety profile.2Langley R.G. Elewski B.E. Lebwohl M. et al.Secukinumab in plaque psoriasis—results of two phase 3 trials.N Engl J Med. 2014; 371: 326-338Crossref PubMed Scopus (1297) Google Scholar 2PRECISE was a phase 3b multicenter, randomized, double-blind, placebo-controlled, parallel-group study comparing secukinumab 300 mg (n = 79) and 150 mg (n = 80) to placebo (n = 78) in individuals with moderate to severe palmoplantar pustular psoriasis over 52 weeks. The primary objective was a response of at least a 75% reduction in Palmoplantar Pustular Psoriasis Area Severity Index (ppPASI75) with secukinumab at week 16 versus placebo.3Mrowietz U. Bachelez H. Burden A.D. et al.Secukinumab for moderate-to-severe palmoplantar pustular psoriasis: results of the 2PRECISE study.J Am Acad Dermatol. 2019; 80: 1344-1352Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar Baseline patient characteristics, study design, and primary endpoint were previously reported.3Mrowietz U. Bachelez H. Burden A.D. et al.Secukinumab for moderate-to-severe palmoplantar pustular psoriasis: results of the 2PRECISE study.J Am Acad Dermatol. 2019; 80: 1344-1352Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar Extension of treatment after week 52 was possible to up to 148 weeks, with patients who achieved meaningful clinical response in the investigator's judgment either maintained on secukinumab 300 mg (n = 36) or secukinumab 150 mg (n = 31) and placebo nonresponder patients who had switched to secukinumab 300 mg (n = 17) or 150 mg (n = 10) at week 16 of the core study.3Mrowietz U. Bachelez H. Burden A.D. et al.Secukinumab for moderate-to-severe palmoplantar pustular psoriasis: results of the 2PRECISE study.J Am Acad Dermatol. 2019; 80: 1344-1352Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar Missing values were imputed using the last observation carried forward (LOCF). The mean ppPASI at study baseline was 22.7 (standard deviation, 9.5) in patients who entered the extension period. The ppPASI75 response rates increased during the extension period in all groups (Fig 1). At week 148, the percentages of patients with ppPASI75 response had increased in all groups, with similar levels in the placebo/secukinumab 150 mg group (75.0%), placebo/secukinumab 300 mg group (77.8%), and initial secukinumab 300 mg group (78.3%), and 100% responders in the initial secukinumab 150 mg group. At the end of the extension treatment period at week 148, the mean ppPASI in the placebo/secukinumab 150 mg group remained at the same level, at 9.75, whereas it had decreased in all other groups (initial secukinumab 150 mg, 1.01; initial secukinumab 300 mg, 3.43; and placebo/secukinumab 300 mg, 4.19) (Fig 2). The overall incidence of adverse events in the extension treatment period was slightly lower under secukinumab 150 mg (61.0%) than under secukinumab 300 mg (69.8%), and no new or unexpected adverse events were observed. During the extension period, there were 5 discontinuations in the secukinumab 150 mg group (16.1%), 5 in the secukinumab 300 mg group (13.9%), 4 in the placebo/secukinumab 150 mg group (40.0%), and 4 in the placebo/secukinumab 300 mg group (23.5%).Fig 2Time course of mean absolute ppPASI score during extension treatment period (full analysis set, last observation carried forward). ppPASI, Palmoplantar Pustular Psoriasis Area Severity Index; Pts, patients; Sec, secukinumab.View Large Image Figure ViewerDownload Hi-res image Download (PPT) The low numbers of patients in each group warrant caution in interpreting these results and render unfeasible any further analysis of efficacy by patient characteristics on entering the extension study. The apparently greater benefit observed for the 150-mg dose compared to the 300-mg dose may also be due to small group numbers and discontinuations. However, these data suggest a sustained clinical benefit and an acceptable safety and tolerability profile of extended treatment with secukinumab 300 mg or 150 mg in patients with palmoplantar pustular psoriasis who had achieved a meaningful clinical response at weeks 16 and 52 when continuing secukinumab up to week 148.