title: Cardiovascular and cerebrovascular events among patients receiving omalizumab: Results from EXCELS, a prospective cohort study in moderate to severe asthma.
abstract: BACKGROUND
  EXCELS, a postmarketing observational cohort study, was a commitment to the US Food and Drug Administration to assess the long-term safety of omalizumab in an observational setting, focusing predominantly on malignancies.
  
  
  OBJECTIVE
  The aim of this study was to examine a potential association between omalizumab and cardiovascular (CV)/cerebrovascular (CBV) events in EXCELS.
  
  
  METHODS
  Patients (≥12 years of age) with moderate to severe allergic asthma and who were being treated with omalizumab (n = 5007) or not (n = 2829) at baseline were followed up for ≤5 years. Analyses included overall CV/CBV events, but focused on the subset of arterial thromboembolic events (ATEs), comprising CV death, myocardial infarction, ischemic stroke, transient ischemic attack, and unstable angina. A prespecified analysis of the end point of ATE was conducted to control for available potential confounders. A blinded independent expert panel adjudicated all events.
  
  
  RESULTS
  At baseline, the 2 cohorts had similar demographic characteristics, but severe asthma was more common in the omalizumab versus the non-omalizumab group (50% vs 23%). Omalizumab-treated patients had a higher rate of CV/CBV serious adverse events (13.4 per 1,000 person years [PYs]) than did non-omalizumab-treated patients (8.1 per 1,000 PYs). The ATE rates per 1,000 PYs were 6.66 (101 patients/15,160 PYs) in the omalizumab cohort and 4.64 (46 patients/9,904 PYs) in the non-omalizumab cohort. After control for available confounding factors, the hazard ratio was 1.32 (95% CI, 0.91-1.91).
  
  
  CONCLUSIONS
  This observational study demonstrated a higher incidence rate of CV/CBV events in the omalizumab versus the non-omalizumab cohort. Differences in asthma severity between cohorts likely contributed to this imbalance, but some increase in risk cannot be excluded.
authors.affiliation: Division of Research, Kaiser Permanente Medical Care Program, Oakland, Calif.
authors.forename: Carlos
authors.initials: C
authors.lastname: Iribarren
authors.affiliation: Genentech, Inc, South San Francisco, Calif. Electronic address: abdelkar@gene.com.
authors.forename: Abdelkader
authors.initials: A
authors.lastname: Rahmaoui
authors.affiliation: Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston; Harvard Medical School, Cambridge, Mass.
authors.forename: Aidan A
authors.initials: AA
authors.lastname: Long
authors.affiliation: Pediatric Asthma Research Program, Breathing Institute, Children's Hospital Colorado and the University of Colorado School of Medicine, Aurora, Colo.
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Szefler
authors.affiliation: Genentech, Inc, South San Francisco, Calif.
authors.forename: Mary S
authors.initials: MS
authors.lastname: Bradley
authors.affiliation: Genentech, Inc, South San Francisco, Calif.
authors.forename: Gillis
authors.initials: G
authors.lastname: Carrigan
authors.affiliation: Genentech, Inc, South San Francisco, Calif.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Eisner
authors.affiliation: Genentech, Inc, South San Francisco, Calif.
authors.forename: Hubert
authors.initials: H
authors.lastname: Chen
authors.affiliation: Genentech, Inc, South San Francisco, Calif.
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Omachi
authors.affiliation: Peter Munk Cardiac Centre and the Heart and Stroke Richard Lewar Centre of Excellence, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Farkouh
authors.affiliation: RTI Health Solutions, Research Triangle Park, NC.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Rothman
mesh_terms: D000328:Adult; D018927:Anti-Asthmatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D002561:Cerebrovascular Disorders / Q000453:epidemiology*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D000069444:Omalizumab / Q000009:adverse effects* / Q000627:therapeutic use; D011358:Product Surveillance, Postmarketing; D011446:Prospective Studies
chemical_list: D018927:Anti-Asthmatic Agents; D000069444:Omalizumab
keywords: Adverse event; arterial thromboembolic event; clinical trials; moderate to severe asthma; omalizumab; safety; serious adverse event