Long-term Safety of Secukinumab Over Five Years in Patients with Moderate-to-severe Plaque Psoriasis, Psoriatic Arthritis and Ankylosing Spondylitis: Update on Integrated Pooled Clinical Trial and Post-marketing Surveillance Data

Abstract

Secukinumab, a selective interleukin (IL)-17A inhibitor, is approved for use in adult and paediatric psoriasis, psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondyloarthritis. The aim of this study was to report the long-term safety of secukinumab in pooled data from 28 clinical trials and a post-marketing safety surveillance in psoriasis, psoriatic arthritis and ankylosing spondylitis patients. Analyses included 12,637 secukinumab-treated patients, corresponding to 15,063, 5,985 and 3,527 patient-years of exposure in psoriasis, psoriatic arthritis and ankylosing spondylitis patients, respectively. Incidences of serious adverse events were low, with no identifiable patterns across indications. Active tuberculosis or latent tuberculosis infections were rare. The incidence of opportunistic infections was < 0.2/100 patient-years, the incidence of malignancy was ≤ 1/100 patient-years, and the incidence of major adverse cardiovascular events was < 0.7/100 patient-years, with no apparent increases over time. Secukinumab demonstrated a favourable safety profile for up to 5 years of treatment across the 3 indications, and no new safety signals were identified.

Fig. 1

Studies included in the pooled analysis. AS: ankylosing spondylitis; ETN, etanercept; N: total number of patients per group; N/A: not applicable; PBO: placebo; PsA: psoriatic arthritis; PsO: psoriasis; UST: ustekinumab.

Fig. 2

Incidence of selected adverse events of interest year-by-year with secukinumab. Graphs demonstrating exposure-adjusted incidence rate per 100 patient-years (EAIRs) of special interest in (A) psoriasis (PsO), (B) psoriatic arthritis (PsA) and (C) ankylosing spondylitis (AS) patients. Number of patients included in the analysis: PsO, year 1 (N = 8,819), year 2 (N = 5,917), year 3 (N = 2,257), year 4 (N = 1,627) and year 5 (N = 1,338); PsA: year 1 (N = 2,678), year 2 (N = 2,011), year 3 (N = 1,237), year 4 (N = 813) and year 5 (N = 466); AS: year 1 (N = 1,140), year 2 (N = 1,016), year 3 (N = 847), year 4 (N = 540) and year 5 (N = 403). ^aRates for system organ class; ^bRates for high-level terms; ^cRates for Novartis MedDRA query terms; ^dRates for preferred terms. 95% CI: 95% confidence interval; IBD: inflammatory bowel disease; MedDRA: Medical Dictionary for Regulatory Activities; N: number of patients in the analysis.

Fig. 3

Crude incidence (reporting rate) of adverse events with secukinumab across 6 periodic safety update reporting periods. Graphs demonstrating crude incidence reporting rate/100 patient-years (PY) for malignancy, serious infections, major adverse cardiovascular event (MACE) and inflammatory bowel disease (IBD) across the 3 indications, based on periodic safety update report (PSUR) data from 2014 to 2018. ^aRates for total IBD (unspecified IBD, Crohn’s disease and/or ulcerative colitis). AS: ankylosing spondylitis; EARR: exposure-adjusted reporting rate; N: number of patients in the analysis; PsA: psoriatic arthritis; PsO: psoriasis; PTYRR: patient-treatment years reporting rate.