Journal Article

Long-term safety of secukinumab in patients with moderate-to-severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis: integrated pooled clinical trial and post-marketing surveillance data

Baraliakos, X., Fox, T., Widmer, A., Porter, B., Blauvelt, A., Das Gupta, A., Deodhar, A., McInnes, I. B., Pricop, L., Mease, P. J., Reich, K., Leonardi, C.

2019

Overview

Background Secukinumab, a fully human immunoglobulin G1-kappa monoclonal antibody that directly inhibits interleukin (IL)-17A, has been shown to have robust efficacy in the treatment of moderate-to-severe psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) demonstrating a rapid onset of action and sustained long-term clinical responses with a consistently favorable safety profile in multiple Phase 2 and 3 trials. Here, we report longer-term pooled safety and tolerability data for secukinumab across three indications (up to 5 years of treatment in PsO and PsA; up to 4 years in AS). Methods The integrated clinical trial safety dataset included data pooled from 21 randomized controlled clinical trials of secukinumab 300 or 150 or 75 mg in PsO (14 Phase 3 trials and 1 Phase 4 trial), PsA (3 Phase 3 trials), and AS (3 Phase 3 trials), along with post-marketing safety surveillance data with a cut-off date of June 25, 2017. Adverse events (AEs) were reported as exposure-adjusted incident rates (EAIRs) per 100 patient-years. Analyses included all patients who received ≥ 1 dose of secukinumab. Results A total of 5181, 1380, and 794 patients from PsO, PsA, and AS clinical trials representing secukinumab exposures of 10,416.9, 3866.9, and 1943.1 patient-years, respectively, and post-marketing data from patients with a cumulative exposure to secukinumab of ~ 96,054 patient-years were included in the analysis. The most frequent AE was upper respiratory tract infection. EAIRs across PsO, PsA, and AS indications were generally low for serious infections (1.4, 1.9, and 1.2, respectively), Candida infections (2.2, 1.5, and 0.7, respectively), inflammatory bowel disease (0.01, 0.05, and 0.1, respectively), and major adverse cardiac events (0.3, 0.4, and 0.6, respectively). No cases of tuberculosis reactivation were reported. The incidence of treatment-emergent anti-drug antibodies was low with secukinumab across all studies, with no discernible loss of efficacy, unexpected alterations in pharmacokinetics, or association with immunogenicity-related AEs. Conclusions Secukinumab demonstrated a favorable safety profile over long-term treatment in patients with PsO, PsA, and AS. This comprehensive assessment demonstrated that the safety profile of secukinumab was consistent with previous reports in patients with PsO, PsA, and AS, supporting its long-term use in these chronic conditions.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Ankylosing spondylitis / Antibodies / Antibodies, Monoclonal, Humanized - adverse effects / Antibodies, Monoclonal, Humanized - therapeutic use / Arthritis / Arthritis, Psoriatic - diagnosis / Arthritis, Psoriatic - drug therapy / Biological products / Biologics / Clinical decision making / Clinical trials / Clinical Trials, Phase III as Topic - methods / Clinical Trials, Phase IV as Topic - methods / Cytokines / Decision making / Drug dosages / Drug therapy / Gastrointestinal diseases / Health surveillance / Humans / Immunoglobulins / Inflammatory bowel disease / Interleukin / Interleukins / Marketing / Medicine / Medicine & Public Health / Monoclonal antibodies / Orthopedics / Pathogenesis / Patient outcomes / Patients / Product Surveillance, Postmarketing - methods / Product Surveillance, Postmarketing - trends / Psoriasis / Psoriasis - diagnosis / Psoriasis - drug therapy / Psoriatic arthritis / Randomized Controlled Trials as Topic - methods / Research Article / Respiratory system agents / Rheumatology / Safety / Secukinumab / Severity of Illness Index / Spondylitis / Spondylitis, Ankylosing - diagnosis / Spondylitis, Ankylosing - drug therapy / Spondyloarthritis / Suicides & suicide attempts / Systematic review / Testing / Time Factors / TNF inhibitors / Tuberculosis / Tumor necrosis factor-TNF