Acta Dermato-Venereologica 99-9CompleteContent

769 CLINICAL REPORT IL-17A Inhibitor Switching – Efficacy of Ixekizumab Following Secukinumab Failure. A Single-center Experience Shany SHERMAN 1,2 , Efrat SOLOMON-COHEN 1,2 , Iris AMITAY-LAISH 1,2 , Emmilia HODAK 1,2 and Lev PAVLOVSKY 1,2 1 Division of Dermatology, Rabin Medical Center – Beilinson Hospital, Petach Tikva, and 2 Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Interleukin-17A inhibitors are a promising alterna- tive to tumor necrosis factor-α inhibitors for the treat- ment of psoriasis. In-class switch has been hardly in- vestigated for interleukin-17A inhibitors. We report the experience (2017–2018) of a tertiary medical center with interleukin-17A-inhibitor switch in pa- tients with moderate-to-severe psoriasis. Patient-, disease- and outcome-related data were retrospec- tively collected from the electronic files of 25 patients switched to ixekizumab following secukinumab failure. Mean ± standard deviation patient age was 56.7 ± 12.2 years. Mean baseline Psoriasis Area and Severity In- dex was 25. Secukinumab was discontinued due to primary failure in 7 patients and secondary failure in 18. Ixekizumab was administered for 7.3 ± 2.8 months; 22 patients were still on ixekizumab at the end of the ± standard deviation Psoriasis Area and study. Mean Severity Index reduction from baseline at study end ± 20.0%. Patients with moderate-to-severe was 75.5 psoriasis seem to be amenable to treatment with ixekizumab following secukinumab failure. Further large multicenter studies are needed. Key words: IL-17A-inhibitors; ixekizumab; secukinumab; moderate-to-severe psoriasis; drug survival; switch. Accepted Apr 16, 2019; E-published Apr 16, 2019 Acta Derm Venereol 2019; 99: 769–773. Corr: Lev Pavlovsky, MD PhD, Division of Dermatology, Rabin Medical Center – Beilinson Hospital, Petach Tikva 4941492, Israel. E-mail: levp@ clalit.org.il P soriasis is a chronic immune-mediated inflammatory skin disease that frequently requires life-long treat ment. About 30% of psoriatic patients are considered to have a more severe disease (1). The development of tu mor necrosis factor (TNF)-α inhibitors, including etaner cept, adalimumab (2, 3), and anti-interleukin (IL)-12/23 ustekinumab (3), about 15 years ago, revolutionized the treatment of moderate-to-severe psoriasis. However, according to drug-survival studies, which measure the period of medication use until discontinuation, the ef fectiveness of all TNF-α inhibitors may be expected to decrease in the long-term (4). IL-17A is a key cytokine in the pathogenesis of psoria sis (5). It may be selectively neutralized by secukinumab, a fully human monoclonal antibody. Secukinumab has SIGNIFICANCE The limited arsenal of biologic treatments available for moderate-to-severe psoriasis may make IL-17A in-class switch (secukinumab-to-ixekizumab) necessary, following a primary or secondary failure. Patients with heavily pre- treated moderate-to-severe psoriasis respond well to ixeki- zumab for a relatively long time. The number of previous li- nes of treatment may adversely affect ixekizumab efficacy. shown considerable efficacy in the treatment of modera te-to-severe psoriasis and psoriatic arthritis, with a rapid onset of action, sustained responses, and favorable safety profile (5). However, although an extension of the ori ginal SCULPTURE study of dose regimens in psoriasis treatment reported sustained efficacy of secukinumab over 3 years of treatment (6), the findings were not al ways confirmed in a real-life setting. In a study of several biologic agents (adalimumab, etanercept, infliximab, ustekinumab, and secukinumab), secukinumab was as sociated with the lowest drug survival rate (7). Sequential treatment with two TNF-α inhibitors has been investigated with encouraging results, albeit vari able efficacy (8–14). However, data on IL-17A-inhibitor switching, from secukinumab to ixekizumab, are still preliminary and limited to the short term. Our literature search yielded 3 studies, summarizing 12 weeks of switch (15–17); a case series (n = 12) (15), a multicenter retro spective study of 17 patients (16), and a sequential study including additional 14 patients (17). In another recent multicenter retrospective real-life study of 100 psoriatic patients, treated with ixekizumab, 26 patients underwent a secukimumab-to-ixekizumab switch. Following 12–16 weeks of treatment, 20 patients (77%) achieved a 75% reduction in the Psoriasis and Severity Index (PASI) score (PASI 75) (18). The most recent results were provided by a study summarizing 24 weeks of switch of secukinumab to ixekizumab (19). The two available IL-17A inhibitors, secukinumab and ixekizumab, were registered in Israel for the treatment of moderate-to-severe psoriasis in August 2015 and August 2017, respectively. The aim of the present study is to report an extended period, up to one-year experience of a tertiary medical center in Israel with IL-17A-inhibitor switch in patients with moderate-to-severe psoriasis. This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica. doi: 10.2340/00015555-3200 Acta Derm Venereol 2019; 99: 769–773

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