Carlos Iribarren1, Abdelkader Rahmaoui2, Aidan A Long3, Stanley J Szefler4, Mary S Bradley5, Gillis Carrigan5, Mark D Eisner5, Hubert Chen5, Theodore A Omachi5, Michael E Farkouh6, Kenneth J Rothman7. 1. Division of Research, Kaiser Permanente Medical Care Program, Oakland, Calif. 2. Genentech, Inc, South San Francisco, Calif. Electronic address: abdelkar@gene.com. 3. Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston; Harvard Medical School, Cambridge, Mass. 4. Pediatric Asthma Research Program, Breathing Institute, Children's Hospital Colorado and the University of Colorado School of Medicine, Aurora, Colo. 5. Genentech, Inc, South San Francisco, Calif. 6. Peter Munk Cardiac Centre and the Heart and Stroke Richard Lewar Centre of Excellence, University of Toronto, Toronto, Ontario, Canada. 7. RTI Health Solutions, Research Triangle Park, NC.
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). CONCLUSION: 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.
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). CONCLUSION: 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: Sarfaraz Hasni; Sarthak Gupta; Michael Davis; Elaine Poncio; Yenealem Temesgen-Oyelakin; Elizabeth Joyal; Alice Fike; Zerai Manna; Sungyoung Auh; Yinghui Shi; Diana Chan; Philip Carlucci; Ann Biehl; Barbara Dema; Nicolas Charles; James E Balow; Meryl Waldman; Richard M Siegel; Mariana J Kaplan; Juan Rivera Journal: Arthritis Rheumatol Date: 2019-05-08 Impact factor: 10.995
Authors: Désirée E S Larenas-Linnemann; Claudio A S Parisi; Carla Ritchie; Ricardo Cardona-Villa; Ivan Cherrez-Ojeda; Annia Cherrez; Luis Felipe Ensina; Elizabeth Garcia; Iris V Medina; Mónica Rodríguez-González; Jorge Mario Sánchez Caraballo Journal: Curr Allergy Asthma Rep Date: 2018-05-09 Impact factor: 4.806