Biological agents represent the most advanced type of treatment for psoriasis. Secukinumab is a human monoclonal anti IL-17A antibody that binds to human IL-17A and neutralizes its bioactivity by inhibiting IL17A produced by both Th17 cells and those of the innate immune system, thus providing complete anti IL17A blockage. Targeting IL-17A has the potential to reduce autoimmune inflammation while leaving other immune functions undisturbed. While targeting of Th1-promoting or Th17-promoting cytokines affects critical mediators such as IFN-γ, IL-22 and IL-21, selective targeting of IL-17A leaves these Th1/17 activities, as well as certain protective functions of innate cells intact. Furthermore, as a fully human monoclonal antibody, secukinumab should reduce immunogenic risks compared to current or emerging antibody therapies that are not fully human.~Many recent studies have shown that highly selective biologic drugs are not effective in every patient and that variations in the genome can be associated with different clinical responses or side effects to a given drug. The PSORS1 locus on chromosome 6p is generally understood to confer the most risk for psoriasis. A specific allele for this locus, HLA C*06, is present in about 60% of psoriatic patient cases. Data linking secukinumab efficacy to a particular genetic marker are lacking.~Recent research has revealed a marked difference in the proportion of PASI 90 achievers at 12 weeks between Cw6-positive and Cw6-negative patients (85.7% vs 56.5%) treated with ustekinumab (Talamonti M et al. 2013) and a greater efficacy of anti-TNFα drugs in CW6 negative patients (Galli et al. 2013).Unlike anti-IL-12/23 agents, secukinumab inhibits IL-17 produced by both Th17 cells after presentation by antigen presenting cells (in this case Cw6) and cells of the innate immune system whose activation does not require antigen presentation. Providing a drug that is equally effective on both Cw6-negative and Cw6-positive patients would be an important clinical accomplishment and would eliminate the need for costly HLA-Cw6 tests. The choice of a cohort study would therefore seem appropriate for this clinical context.~The purpose of this study was to explore the different efficacy and safety profile of secukinumab 300 mg in patients with moderate to severe chronic plaque-type psoriasis, stratified for the presence of HLA-C*06, whose determination was blinded for patients and investigators. The study was conducted both on anti-TNFα-naïve and anti-TNFα failure patients and also stratified for TNFα - 308 polymorphism, BMI, smoking and metabolic syndrome, among others.
A study to evaluate the differences in the efficacy and safety of secukinumab between Cw6-negative and Cw6-positive patients with moderate to severe plaque-type psoriasis