Exploratory Evaluation of Biomarkers Associated With Treatment Response to Cosentyx (Secukinumab) in Psoriasis Patients

Psoriasis vulgaris is a chronic inflammatory skin disease which is characterized by raised, well-demarcated, erythematous plaques and affects approximately 2% of the Caucasian population.

Patients suffering from moderate-to-severe psoriasis may be treated with a variety of systemic agents and treatment modalities, including retinoids, phototherapy and/or immunomodulatory drugs, including methotrexate, ciclosporin and fumarates. Patients are regularly monitored to determine the efficacy of treatment and to detect signs of systemic toxicity. Indeed, lack of efficacy and/or therapeutic toxicity are factors which require a re-evaluation of therapy. In addition to the conventional systemic treatments, systemic "biologic" therapies are playing an increasingly important role in the management of moderate to severe psoriasis.These treatments have resulted from advances in the understanding of the patho-physiology of psoriasis, combined with advances in molecular biology, in order to provide a more targeted therapy. Biologics include drugs targeting the production or signal transduction of tumour necrosis factor alpha (TNFα), and more recently, agents which target specific cytokines known to play an important role in the disease, including interleukin (IL) 12/23.

Despite these advances in psoriasis therapy, a relatively small number of patients initially fail to respond to biological psoriasis treatment or relapse during treatment. In fact, treatment with TNFα inhibitors and IL-12/23 monoclonal antibodies fails to induce disease control (PASI 75) in approximately 20-30% of the patients.

An alternative biological therapy, recently licensed for the management of moderate to severe psoriasis is Secukinumab (Cosentyx®). Secukinumab binds to human IL-17A and neutralizes the bioactivity of this cytokine. IL-17A is increasingly recognized as one of the principal pro-inflammatory cytokines in immune mediated inflammatory diseases, including psoriasis. A recombinant, high-affinity, fully human monoclonal anti-human IL-17A antibody of the IgG1/κ class, Secukinumab treatment has reportedly resulted in disease response rates of up to almost 80%, as measured by a 90% improvement in the Psoriasis Area and Severity Index measure (PASI). Moreover, treatment with Secukinumab was associated with superior improvements in quality of life indices (Dermatology Life Quality Index (DLQI) when compared to treatment with the IL12/23 inhibitor Ustekinumab. Given that treatment with biologics is reportedly associated with a loss of response over time, the development of novel classes of biologics, including those targeting IL-17, has been welcomed in terms of expanding the psoriasis treatment armamentarium.

Despite the clinical data supporting the use of Secukinumab in the management of moderate to severe psoriasis, there are currently no molecular tools to identify which patients are likely to respond to treatment. Identifying biomarker(s) of disease response would not only facilitate optimized and personalized treatment, but would also ensure that patients who are unlikely to respond are not exposed to the risks associated with biologic treatments, principally derived from long-term immunosuppression. In addition, given that psoriasis is often associated with several inflammatory diseases, including psoriatic arthritis and inflammatory bowel disease, such biomarkers may also serve a key role in predicting treatment response of those co-morbid conditions to biological therapy.