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.

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.

• Authors: R G Langley, K Papp, A B Gottlieb, G G Krueger, K B Gordon, D Williams, J Valdes, C Setze, B Strober
• Journal: Journal of the European Academy of Dermatology and Venereology : JEADV (J Eur Acad Dermatol Venereol) Vol. 27 Issue 10 Pg. 1252-61 (Oct 2013) ISSN: 1468-3083 [Electronic] England
• PMID: 23157612 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

Chemical References

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

Topics

• Adult
• Antibodies, Monoclonal (adverse effects, immunology, 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