Phase 2 randomized, double-blind study of IL-17 targeting with secukinumab in atopic dermatitis To the Editor:Atopic dermatitis (AD) affects 3% to 10% of adults. 1 Recently, the increased understanding of AD pathogenesis has led to development of new treatments, including dupilumab, the first US Food and Drug Administration-approved biologic for moderate-to-severe AD. Although T H 2 skewing is common across all AD subtypes, as suggested by the efficacy of dupilumab across populations with AD, it is a highly heterogeneous disease with diverse subtypes characterized by varying immune activation, perhaps requiring additional therapeutic approaches. 2,3 Recent studies have shown increased T H 17 skewing in several AD subtypes, including intrinsic, 3 Asian, 2 and pediatric AD, 4 and have also shown that T H 17-related markers are significantly correlated with AD severity. [2][3][4] An Asian patient with AD demonstrated clinical and tissue improvement with secukinumab, a selective IL-17A inhibitor. 5 However, controlled trials with IL-17 antagonists in patients with moderate-to-severe AD (including T H 17-high subtypes) are FIG 1. Epidermal thickness, epidermal hyperplasia markers, and clinical outcomes. A-C, Box plots depicting fold change (FCH) in epidermal thickness (A), Ki67 level (B), and K16 level (C) in lesional skin at week 4 (W4) and W16 versus at baseline (BL) (W0); red stars indicate significance of comparison with baseline. 1 P < .1 and **P < .01. D and E, Mean percentage change 6 SEM for the Scoring Atopic Dermatitis (SCORAD) (D) and the Eczema Area and Severity Index (EASI) (E) scores in all patients with AD receiving secukinumab or placebo from baseline to W16. Red and blue numbers in (D) and (E) represent numbers of patients receiving secukinumab and placebo remaining at each time point, respectively.

IntroductionSecukinumab, a fully human anti-interleukin-17A monoclonal antibody, has demonstrated superior efficacy to ustekinumab in the phase 3b CLEAR study of moderate to severe plaque psoriasis. Here, we report 16-week results from CLARITY, a second head-to-head trial comparing secukinumab with ustekinumab.MethodsIn the phase 3b CLARITY study, patients were randomized 1:1 to receive subcutaneous secukinumab 300 mg or ustekinumab per label. The co-primary objectives were to demonstrate the superiority of secukinumab over ustekinumab at Week 12 in relation to the proportion of patients with (1) 90% or more improvement from baseline Psoriasis Area and Severity Index (PASI 90) and (2) a score of 0/1 (clear/almost clear) on the modified Investigator’s Global Assessment (IGA mod 2011 0/1). Key secondary objectives were also assessed, as was Dermatology Life Quality Index (DLQI) 0/1 (no impact of skin disease on patients’ quality of life) response. Missing values were handled by multiple imputation except for DLQI 0/1, where last observation carried forward techniques were utilized.ResultsBoth co-primary objectives were met: secukinumab was superior to ustekinumab for the proportion of patients achieving a PASI 90 (66.5% vs. 47.9%) and IGA mod 2011 0/1 response (72.3% vs. 55.4%) at Week 12 (p < 0.0001). PASI 90 responses were greater with secukinumab compared to ustekinumab from as early as Week 4 (16.7% vs. 4.0%) and out to Week 16 (76.6% vs. 54.2%). Similarly, IGA mod 2011 0/1 findings were greater with secukinumab at Week 4 (26.9% vs. 7.8%) and at Week 16 (78.6% vs. 59.1%). DLQI 0/1 response rates were also greater with secukinumab compared to ustekinumab at Week 4 (33.9% vs. 18.0%), Week 12 (64.0% vs. 51.7%), and Week 16 (68.4% vs. 55.9%).ConclusionThe results of this study confirm the superior efficacy of secukinumab over ustekinumab in treating patients with moderate to severe psoriasis.Trial RegistrationClinicaltrials.gov Identifier, NCT02826603.FundingNovartis Pharma AG, Basel, Switzerland.Electronic supplementary materialThe online version of this article (10.1007/s13555-018-0265-y) contains supplementary material, which is available to authorized users.

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Alopecia areata is accompanied by Th2/Tc2 activation in skin-homing and systemic subsets, correlating with disease severity, while IFN-γ is linked to disease chronicity. These data hint for a possible role of diverse T-cells subsets in disease pathogenesis and emphasize the systemic nature of AA supporting the need for systemic therapeutic strategies in severe patients.

Alopecia areata (AA) is a common form of non-scarring hair loss. The pathogenesis of AA is believed to involve multiple inflammatory cytokines, including possibly IL-17A. To assess the efficacy and safety of the IL-17A antagonist secukinumab in AA, we conducted a double-blinded, randomized prospective pilot study in which 11 subjects were treated with either secukinumab (n = 7) or placebo (n = 4) subcutaneously at weeks 0, 1, 2, 3, 4 and every 4 weeks thereafter until (inclusive of) week 20. The primary endpoint for the study was the percentage of patients achieving SALT50 at 24 weeks. A total of three subjects out of 11 completed the study through the primary endpoint, and therefore, we used the last observation carried forward method to analyze the missing data. At the primary endpoint or last completed observation, 0% (0/7) of the secukinumab-treated subjects achieved a 50% reduction in SALT score (SALT50), and likewise, 0% (0/4) of the placebo-treated subjects achieved SALT50. In the secukinumab group, one (14.3%) subject had some hair regrowth, one (14.3%) subject had worsening hair loss, and five (71.4%) subjects had no change in response to treatment. No adverse events attributable to the study drug were observed. The lack of a treatment response to most of our treated patients suggests that the T17/IL-17 axis likely has no pathogenic role in AA and an alternative therapeutic approach should be considered for this disease. However, due to the low statistical power of this study, future studies may be required to corroborate these findings.