title: Association of ustekinumab and briakinumab with major adverse cardiovascular events: An appraisal of meta-analyses and industry sponsored pooled analyses to date.
abstract: Safety concerns have been raised regarding possible association of major adverse cardiovascular events (MACEs) with use of anti-IL-12/23 biologic agents for the treatment of chronic plaque psoriasis (CPP). Ten MACEs have been recorded in actively-treated patients during the placebo-controlled phase of phase II and III studies compared with zero events in placebo-treated patients, along with a total of 53 MACEs (26 ustekinumab, 27 briakinumab) and five cardiovascular deaths (1 ustekinumab, 4 briakinumab) across all phases of these studies. Two industry-independent meta-analyses of randomized, double-blind, placebo-controlled, monotherapy trials calculated risk for MACEs. One detected statistically significant increase in cardiovascular risk using Peto method (p = 0.04), while the other utilized Mantel-Haenszel fixed-effects model with absolute risk differences as effect measure, but did not achieve significance (p = 0.11). Statistical theory reports that Peto method is more suitable for meta-analyses of studies with baseline event rates of 1% or less and randomization ratios ranging from 1:5 to 1:1 as is the case in these meta-analyses. Potential of anti-IL-12/23 biologic agents to further increase cardiovascular morbidity cannot be excluded and a class effect cannot be denied. Clinicians should screen CPP patients for manageable cardiovascular risk factors before initiating anti-IL-12/23 agents along with intensive monitoring of these patients.
authors: Division of Evidence Based Dermatology; Departments of Dermatology, Venereology, Allergology and Immunology; Dessau Medical Center; Dessau, Germany ; Hospital for Skin and Venereal Diseases; Thessaloniki, Greece.
authors: Thrasivoulos
authors: T
authors: Tzellos
authors: Athanassios
authors: A
authors: Kyrgidis
authors: Anastasia
authors: A
authors: Trigoni
authors: Christos C
authors: CC
authors: Zouboulis
keywords: briakinumab; chronic plaque psoriasis; major adverse cardiovascular events; meta-analysis; ustekinumab