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.