Faculty Collaboration Database

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

Date

11/20/2012

Pubmed ID

23157612

DOI

10.1111/j.1468-3083.2012.04705.x

Scopus ID

2-s2.0-84884900971 (requires institutional sign-in at Scopus site)   59 Citations

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.

Author List

Langley RG, Papp K, Gottlieb AB, Krueger GG, Gordon KB, Williams D, Valdes J, Setze C, Strober B

Author

Kenneth Brian Gordon MD Chair, Professor in the Dermatology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Carcinoma, Basal Cell
Carcinoma, Squamous Cell
Cardiovascular Diseases
Clinical Trials as Topic
Female
Humans
Interleukin-12
Interleukin-23
Male
Middle Aged
Prevalence
Psoriasis
Randomized Controlled Trials as Topic
Severity of Illness Index
Skin Diseases, Infectious
Skin Neoplasms
Treatment Outcome