Secukinumab (AIN457) for the treatment of psoriasis

Abstract

Psoriasis is a chronic inflammatory disease with a multifactorial origin that appears in patients with genetic predisposition and is induced by environmental factors, and characterized by alterations in the innate and adaptive immunity. IL-17A is one of the specific cytokines involved in the pathogenesis of psoriasis and its inhibition is highly effective in the treatment of patients with moderate and severe psoriasis. Secukinumab is a monoclonal antibody that specifically binds to IL-17A and inhibits the interaction to its receptor, and it has demonstrated its efficacy and safety in the treatment of psoriasis. Phase II and III clinical trials indicate that > 80% of the patients receiving secukinumab achieve Psoriasis Area Severity Index (PASI) 75 at week 12. In the Phase III efficacy of response and safety of two fixed secukinumab regimens in psoriasis trial, PASI 75 rates were 81.6% with 300 mg secukinumab, 71.6% with 150 mg secukinumab and 4.5% with placebo, and responses were maintained up to 52 weeks in the majority of patients. In the Phase III Full Year Investigative Examination Of Secukinumab versus Etanercept Using Two Dosing Regimens To Determine Efficacy in Psoriasis study, the efficacy of secukinumab was compared to etanercept. The results indicate that both doses of secukinumab (150 and 300 mg) showed superior efficacy compared with etanercept throughout the study; PASI 75 rates at week 12 were 77.1% with 300 mg secukinumab, 67% with 150 mg of secukinumab, 44% with etanercept and 4.9% with placebo. PASI 90 and PASI 100 were 54 and 24% with secukinumab 300 mg and 21 and 4% with etanercept at week 12. At week 52, PASI 90 continued to be higher in the secukinumab group (65%) compared with the etanercept group (33%). Regarding safety, the most common side effects were nasopharyngitis and headache. The rate of infections was higher with secukinumab than placebo. This was especially the case for Candida infections, which were more common in the secukinumab group (4.7% with secukinumab 300 mg and 2.3% with secukinumab 150 mg), but all cases were resolved with conventional treatment. Secukinumab is a well-tolerated treatment that has demonstrated efficacy in treating moderate-to-severe plaque psoriasis. Nevertheless, long-term studies are necessary to confirm Phase II and Phase III data.

Keywords:

• IL-17 inhibitors
• psoriasis
• secukinumab
• treatment

Financial & competing interests disclosure

A Lopez-Ferrer has received consultancy/speaker’s honoraria from Janssen. E Vilarrasa has received consultancy/speaker’s honoraria from Abbvie and Janssen. L Puig has been the recipient of grants/research support from Abbvie, Amgen, Janssen, Lilly, Novartis, Pfizer, and VBL. L Puig has received consultancy/speaker’s honoraria from Abbvie, Almirall, Amgen, Boehringer, Celgene, Gebro, Janssen, Leo-Pharma, Lilly, Merck-Serono, MSD, Novartis, Pfizer, Sandoz, and VBL. L Puig has participated in a company sponsored speaker’s bureau for Celgene, Janssen, MSD, Novartis, and Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Secukinumab is a human IgG1 monoclonal antibody that selectively binds to the IL-17A cytokine and inhibits the interaction with its receptor.

• IL-17A is a pro-inflammatory cytokine that is usually involved in normal inflammatory and immune responses.

• IL-17A has a crucial role in the pathogenesis of psoriasis.

• Secukinumab has demonstrated efficacy in treating moderate-to-severe plaque psoriasis in several Phase I, II and III studies, including > 3990 adult patients. Extension studies are ongoing to obtain longer term safety and efficacy data.

• Secukinumab has shown superior efficacy to etanercept (Full Year Investigative Examination of Secukinumab versus Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis study) and ustekinumab (CLEAR study) with similar safety in two randomized controlled trials.

• The most common adverse events reported in the clinical trials were worsening of disease, nasopharyngitis, upper-respiratory-tract infection, arthralgia, injection-site erythema, pain in the extremities, nausea, headache and pruritus.

• The safety profile of secukinumab was comparable with those of etanercept and ustekinumab.

• Secukinumab has been approved by the EMA and the FDA for the treatment of moderate-to-severe psoriasis since January 2015.