BACKGROUND: EXCELS was a postmarketing commitment to the US Food and Drug Administration to assess long-term safety of omalizumab in an observational setting, focusing predominantly on malignancies.
OBJECTIVE: To examine a potential association between omalizumab and cardiovascular (CV)/cerebrovascular (CBV) events in EXCELS.
METHODS: Cohort study of patients (≥12 years of age) with moderate-to-severe allergic asthma followed ≤5 years, treated with omalizumab (n = 5007) or not treated with omalizumab (n = 2829) at baseline. Analyses included overall CV/CBV events, but focused on the subset of arterial thromboembolic events (ATE), comprising CV death, myocardial infarction, ischemic stroke, transient ischemic attack, or unstable angina. A prespecified analysis for the endpoint of ATE was conducted to control for available potential confounders. A blinded independent expert panel adjudicated all events.
RESULTS: At baseline, cohorts had similar demographic characteristics, but severe asthma was more common in the omalizumab versus non-omalizumab cohorts (50% vs 23%). Omalizumab-treated patients had a higher rate of CV/CBV serious adverse events (13.4 per 1000 person-years [PY]) than non-omalizumab-treated patients (8.1 per 1000 PY). ATE rate per 1000 PY was 6.66 (101 patients/15,160 PY) for the omalizumab cohort and 4.64 (46 patients/9904 PY) for the non-omalizumab cohort. After controlling for available confounding factors, the hazard ratio was 1.32 (95% CI, 0.91-1.91).
CONCLUSION: Results from this observational study demonstrated a higher incidence rate of CV/CBV events in the omalizumab versus non-omalizumab cohorts. Differences in asthma severity between cohorts likely contributed to this imbalance, but some increase in risk cannot be excluded (NCT00252135).
CLINICAL IMPLICATIONS: Current asthma management guidelines should not be affected. However, health professionals should be aware of a possible association of omalizumab and serious cardiovascular/cerebrovascular events.
