Safety results from a pooled analysis of randomized, controlled phase II and III clinical trials and interim data from an open-label extension trial of the interleukin-12/23 monoclonal antibody, briakinumab, in moderate to severe psoriasis

J Eur Acad Dermatol Venereol. 2013 Oct;27(10):1252-61. doi: 10.1111/j.1468-3083.2012.04705.x. Epub 2012 Nov 16.

Abstract

Background: Anti-interleukin-12/23 treatment (anti-IL-12/23) has recently demonstrated significant efficacy for moderate to severe psoriasis, yet potential safety signals warrant further investigation.

Objectives: Expand safety findings for the anti-IL-12/23, briakinumab, beyond individual phase II and III clinical trials.

Methods: Safety data pooled from five phase II and III clinical trials (parent studies) and an open-label extension study (OLE), through 22 October 2010; patients with ≥ 1 dose of briakinumab in a parent study or the OLE are included. All parent study briakinumab treatment groups were combined with the OLE population, which received 100-mg briakinumab every 4 weeks. Adverse events (AEs) were collected from the first dose of briakinumab, whether in a parent study or the OLE, through 45 days post-last dose.

Results: Two thousand five hundred and twenty patients (4704 patient-years drug exposure) received ≥ 1 dose of briakinumab during the interim period: 5.6% withdrew due to AEs. Serious infections occurred in 1.3% and malignancies in 2.6% (including 1.0% basal cell carcinoma, 0.8% squamous cell carcinoma). Twenty-seven major adverse cardiovascular events (MACE) occurred, seven in one parent study and 20 in the OLE (incidence = 0.57 events/100 PY). Four cardiovascular risk factors were retrospectively found to be significant predictors for MACE during briakinumab exposure: history of cardiovascular disease, diabetes, body mass index (≥ 30) and baseline blood pressure (systolic ≥ 140 or diastolic ≥ 90).

Conclusions: Pooled briakinumab safety results from five parent studies and an OLE suggest increased rates of infections, malignancies and MACE, and that patients receiving anti-IL-12/23 treatment for moderate to severe psoriasis should be monitored for these potential safety signals.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Carcinoma, Basal Cell / epidemiology
  • Carcinoma, Squamous Cell / epidemiology
  • Cardiovascular Diseases / epidemiology
  • Clinical Trials as Topic
  • Female
  • Humans
  • Interleukin-12 / immunology
  • Interleukin-23 / immunology
  • Male
  • Middle Aged
  • Prevalence
  • Psoriasis / drug therapy*
  • Randomized Controlled Trials as Topic
  • Severity of Illness Index
  • Skin Diseases, Infectious / epidemiology
  • Skin Neoplasms / epidemiology
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Interleukin-23
  • Interleukin-12
  • briakinumab