While European Drug Regulators Have Been Concerned About This Aspect Of Xolair Safety, FDA Has No Warning About Arteriothrombotic Risks Of Xolair
(Posted by Tom Lamb at DrugInjuryWatch.com)
In September 2014 the FDA issued an update about its safety review of the Genentech asthma medication Xolair (omalizumab), which we reported about in this earlier post, "Xolair Asthma Drug Associated With Higher Rate Of Heart Attacks, Pulmonary Hypertension, Blood Clots Causing PEs And/Or DVTs, And Brain Blood Vessel Problems".
From the Data Summary of that September 26, 2014 FDA Drug Safety Communication:
The manufacturer of Xolair, Genentech, initiated the postmarketing commitment study titled An Epidemiologic Study of Xolair (omalizumab): Evaluating Clinical Effectiveness and Long-Term Safety in Patients with Moderate to Severe Asthma (EXCELS) in June 2004 to assess the long-term safety of Xolair
A higher incidence rate per 1,000 patient years of overall cardiovascular and cerebrovascular serious adverse events was observed in Xolair-treated patients compared to non-Xolair-treated patients, as well as for myocardial infarction, unstable angina, transient ischemic attack, pulmonary embolism/venous thrombosis, and pulmonary hypertension. No increases in the rates of ischemic stroke or cardiovascular death were observed in patients treated with Xolair compared to non-Xolair-treated patients.
In this post we consider a medical journal article which takes issue with that last sentence as it reached the opposite conclusion; specifically, Xolair is associated with an increased risk of arterial thrombotic events, predominantly cardiovascular deaths and strokes.
The subject article is "Assessing the association between omalizumab and arteriothrombotic events through spontaneous adverse event reporting", initially published online by the Journal of Asthma and Allergy back in May 2012.
Strictly Confidential, No Obligation.
This 2012 journal article came from two medical researchers at the Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, who wanted to analyze the association between Xolair and arterial thrombotic events. In the Introduction part of their article they noted:
In February 2011, the UK Medicines and Healthcare Products Regulatory Agency advised prescribers to be vigilant about the possible occurrence of arterial thrombotic events in patients exposed to [Xolair (omalizumab)].... These recommendations were based on interim analyses of randomized clinical trials and an unpublished cohort study, ie, EXCELS (Evaluating Clinical Effectiveness and Long- Term Safety in patients with Moderate-to-Severe Asthma). These analyses yielded a statistically insignificant increase in the risk of arterial thrombotic events in groups exposed to [Xolair (omalizumab)] compared with their unexposed control counterparts.... The FDA reviewed the reported adverse events for [Xolair (omalizumab)] in July 2009, and concluded with a warning to prescribers and patients about hypersensitivity reactions, with no reference to any arteriothrombotic risks. This study assessed the safety profile of [Xolair (omalizumab)] with respect to arterial thrombotic events recorded in the FDA Adverse Event Reporting System (AERS) database [from the period 1/1/2004 to 1/1/2011].
According to these University of Florida researchers, their study is the first pharmacovigilance analysis to detect from a spontaneous event reporting database such as the FDA AERS a strong safety signal for Xolair as regards cardiovascular death and stroke events.
From the Results section, in particular "Reporting odds ratio data mining algorithm results":
Cardiovascular death and stroke ranked first on the arterial thrombotic events list in detection of statistically significant safety signals (reporting odds ratio 3.14, 95% CI 2.14–4.56; reporting odds ratio 3.14, 95% CI 2.41–4.05, respectively). Although the reporting odds ratio values for ischemic heart disease, myocardial infarction, and thrombosis risk exceeded 2.0, the lower limit of the 95% CI failed to reach that threshold, making the estimates less significant as safety signals (reporting odds ratio 2.63, 95% CI 1.92–3.63; reporting odds ratio 2.55, 95% CI 1.98–3.29; reporting odds ratio 2.19, 95% CI 1.18–4.01, respectively).
Numerous times throughout their article the authors acknowledge the limitations of their research methods and state that epidemiological studies are necessary to further explore the apparent association of Xolair with cardiovascular deaths, strokes, and other arterial thrombotic adverse events.
Their Xolair analytical study, however, does serve to expand one's range of concern about the drug safety profile for Xolair, which has been available in the US since June 2003.