title: 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.
  
  
  OBJECTIVE
  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.affiliation: Dalhousie University, Halifax, NS, Canada Probity Medical Research, Waterloo, ON, Canada Tufts Medical Centre, Boston, MA, USA University of Utah Health Sciences Centre, Salt Lake City, UT, USA Northwestern University, Evanston, IL, USA Abbott Laboratories, Abbott Park, IL, USA University of Connecticut School of Medicine, Farmington, CT, USA.
authors.forename: R G
authors.initials: RG
authors.lastname: Langley
authors.forename: K
authors.initials: K
authors.lastname: Papp
authors.forename: A B
authors.initials: AB
authors.lastname: Gottlieb
authors.forename: G G
authors.initials: GG
authors.lastname: Krueger
authors.forename: K B
authors.initials: KB
authors.lastname: Gordon
authors.forename: D
authors.initials: D
authors.lastname: Williams
authors.forename: J
authors.initials: J
authors.lastname: Valdes
authors.forename: C
authors.initials: C
authors.lastname: Setze
authors.forename: B
authors.initials: B
authors.lastname: Strober
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002280:Basal Cell Carcinoma / Q000453:epidemiology; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000453:epidemiology; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology; D053759:Interleukin-23 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011565:Psoriasis / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D012874:Skin Diseases, Infectious / Q000453:epidemiology; D012878:Skin Neoplasms / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053759:Interleukin-23; D018664:Interleukin-12; C544528:briakinumab