Rationale and Early Clinical Data on IL-17 Blockade in Psoriasis

Steven M Nwe; Amanda H Champlain; Kenneth B Gordon

Disclosures

Expert Rev Clin Immunol. 2013;9(7):677-682. 

In This Article

Secukinumab

The third IL-17-targeted therapy is secukinumab, a human, monoclonal IgG1 antibody targeting IL-17A. In its proof of concept study, secukinumab was administerd via intravenous infusion at a dose of 3 mg/kg. Thirty six subjects were enrolled and showed responses as early as 4 weeks. In a Phase II placebo-controlled, randomized, double-blind, parallel group study, 404 subjects were assigned in a 1:2:2:1 ratio to receive subcutaneously injected secukinumab at 150 mg in either a one-time dose, a monthly dose, an early dose schedule (at weeks 0, 1, 2 and 4) or placebo.[62] At 12 weeks, 10.6, 42, 54.5 and 1.5% of the subjects achieved a PASI 75 in the one-time dose, monthly dose, early dose and placebo arms respectively. The monthly and early dosing PASI 75 percentages were clinically significant when compared with placebo, while the one-time dose was not.

The most frequent adverse events reported were nasopharyngitis, headache and worsening of psoriasis. Infections were rated either mild or moderate in severity. Five subjects withdrew from the study because of adverse events, including two patients who had erythrodermic psoriasis in the early dosing arm. A total of 20 subjects experienced grade 1 or 2 level neutropenia, but none of these subjects withdrew from the study.

Following week 12, subjects who had achieved a PASI 75 entering the 20-week maintenance period were re-randomized to either a fixed interval arm (150 mg at weeks 12 and 24) or treatment at start of relapse arm (secukinumab 150 mg at the start of relapse defined as a loss of a third of the maximum PASI improvement achieved). Subjects in the fixed interval arm had superior likelihood of PASI75 achievement at least once between the weeks 20 and 28 than those in the start-of-relapse arm, although at 15 weeks postfinal dosing, only 10% of the patients in either arm experienced a start of relapse. The authors of the study inferred from this data that secukinumab would offer dosing flexibility for patients and physicians. A Phase III study is currently ongoing comparing secukinumab at 150 and 300 mg via subcutaneous injection to placebo.

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