Cardiovascular safety of ustekinumab in patients with moderate to severe psoriasis: results of integrated analyses of data from phase II and III clinical studies

Br J Dermatol. 2011 Apr;164(4):862-72. doi: 10.1111/j.1365-2133.2011.10257.x.

Abstract

Background: Patients with psoriasis are believed to be at an increased risk of cardiovascular (CV) morbidity, and the effect of biological agents on CV safety is not fully understood.

Objectives: To evaluate the effect of ustekinumab on CV events using detailed analyses of pooled data from the phase II/III clinical studies of its use in moderate to severe psoriasis.

Methods: The incidence of major adverse CV events [MACE: myocardial infarction (MI), stroke or CV death] is reported. Meta-analyses using risk difference and odds ratio estimates are presented based on data collected during the placebo-controlled period of ustekinumab trials. The cumulative numbers of events and rates of MIs and strokes over time were compared with those expected in the psoriasis and/or general populations.

Results: During the placebo-controlled period (12/20 weeks), five MACE were reported in 1582 ustekinumab-treated patients [0·3%; 95% confidence interval (CI) 0·1-0·7%] compared with no events in 732 placebo-treated patients (0·0%; 95% CI 0·0-0·5%). MACE rates were stable over time during both the controlled and uncontrolled study periods, with 19 of 3117 ustekinumab-treated patients (0·6%) experiencing 21 events for a combined event rate per 100 patient-years of follow-up of 0·44 (95% CI 0·27-0·67) through up to 3 years. Standardized incidence ratios for comparison of ustekinumab clinical data with external data sources ranged from 0·34 to 0·52, suggesting no increased risk of MI or stroke in ustekinumab-treated patients compared with the general U.S. and psoriasis populations.

Conclusions: The totality of available clinical data suggests neither a detrimental nor a beneficial effect of ustekinumab on serious CV events. Additional data are needed to define the net effect of ustekinumab on CV events.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal, Humanized
  • Female
  • Humans
  • Immunologic Factors / adverse effects*
  • Incidence
  • Male
  • Middle Aged
  • Myocardial Infarction / chemically induced*
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / mortality
  • Odds Ratio
  • Psoriasis / complications
  • Psoriasis / drug therapy*
  • Risk Factors
  • Severity of Illness Index
  • Stroke / chemically induced*
  • Stroke / epidemiology
  • Stroke / mortality
  • Ustekinumab

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Immunologic Factors
  • Ustekinumab