Long-term Safety of Secukinumab (Cosentyx) in PsO, PsA, and AS

A recent trial found that secukinumab ( cosentyx ) is a safe and well-tolerated option for the long-term treatment of moderate-to-severe plaque psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS).

Secukinumab, a human immunoglobulin G1-kappa monoclonal antibody, inhibits interleukin-17A. Previous studies have found favorable long-term clinical outcomes and safety profiles.

“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),” wrote the researchers in the present study, published in Arthritis Research & Therapy.

The study authors reviewed data from 21 randomized controlled trials evaluating secukinumab (300 mg, 150 mg, or 75 mg) use in PsO (14 phase 3 trials, one phase 4 trial), PsA (three phase 3 trials), and AS (three phase 3 trials); all patients received at least one dose of the medication. The researchers also evaluated post-marketing safety surveillance data from Dec. 26, 2014, through June 25, 2017; they reported adverse events (AEs) as exposure-adjusted incident rates (EAIRs) per 100 patient-years.

Safety, AEs Associated with Secukinumab

The final analysis included 5,181 PsO patients, 1,380 PsA patients, and 794 AS patients, comprising of secukinumab exposures of 10,416.9, 3866.9, and 1943.1 patient-years, respectively; post-marketing data from patients with cumulative secukinumab exposure of about 96,054 patient-years were available.

EAIR rates for any serious AE with secukinumab treatment were 6.9, 7.9, and 6.3 per 100 patient-years among PsO, PsA, and AS patients, respectively.

Upper respiratory tract infection was the most common AE. All three diseases had low EAIRs for serious infections (PsO, 1.4; PsA, 1.9; AS, 1.2), 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). There were no incidences of tuberculosis reactivation.

There were nine (0.2%) deaths in the PsO group; the most common causes of death were pulmonary embolism, arrhythmia, alcohol poisoning, ruptured aneurysm, and myocardial infarction among 300 mg-dose patients and cerebral hemorrhage, cardiorespiratory arrest, and completed suicide in the 150 mg-dose group. The PsA cohort had 11 (0.8%) deaths, which were attributed to acute myocardial infarction, septic shock, sepsis, pneumonia, metastatic small cell lung cancer, pancreatic carcinoma, and cardiac failure in the 150 mg-dose group, and squamous cell carcinoma of the pharynx, myocardial infarction, and cerebrovascular event in the 75 mg-dose group. Five (0.6%) deaths occurred in the AS patients. One patient taking 150 mg of secukinumab died, and the cause of death was unknown. Four patients taking 75 mg of secukinumab died due to acute respiratory failure, cerebrovascular accident, acute myocardial infarction, and respiratory arrest.

“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,” the authors observed.

Discontinuation rates due to AEs were similar across the three groups: 331 (6.4%) for PsO patients, 104 (7.5%) for PsA patients, and 58 (7.3%) for AS patients.

“Secukinumab demonstrated a favorable safety profile over long-term treatment in patients with PsO, PsA, and AS,” the study authors concluded, adding, “This long-term (up to 5 years) safety assessment provides a broader understanding of the safety of secukinumab and supports its long-term use in these chronic systemic inflammatory conditions.”

Long term safety of Secukinumab in PsO, PsA, & AS RCTs ( 96,054 patient-years) – favorable results with low incidence of serious infx (1.4, 1.9, 1.2, /100PYs), Candida (2.2, 1.5, 0.7/100pYs), IBD (0.01, 0.05, and 0.1/100PYs) or MACE (0.3, 0.4, 0.6). No TB. https://t.co/BTbBlOYj8W

— Dr. John Cush (@RheumNow) May 8, 2019