Increased risk of thrombotic events (TEs), especially thrombotic microangiopathies (TMAs), occurred with concomitant use of emicizumab, according to an updated safety analysis presented at the 63rd American Society for Hematology Annual Meeting & Exposition.
Prothrombin complex concentrate (aPCC) was activated to prophylactically treat individuals with congenital hemophilia A with and without factor VIII inhibitors. No TMAs occurred in patients receiving only emicizumab, however, investigators observed that TEs were markedly associated with advanced age, presence of FVIII inhibitors, cardiovascular comorbidities, and increased risk of thrombosis.
Investigators identified 52 cases of patients with congenital hemophilia A who experienced TEs or TMAs while on emicizumab in the Roche Global Safety Database up until May 15, 2021. Of these cases, 2 were duplicates, 10 were off-label studies, and 1 patient’s diagnosis of hemiparesis did not fit the definition of a true TE, leaving 39 cases for inclusion in this study.
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The researchers analyzed data, including the numbers of TEs/TMAs, clinical indications, age, FVIII inhibitor status, comorbidities, and drug factors to determine any correlations with emicizumab use with and without concomitant aPCC.
Thirty-seven TEs and no TMAs occurred in the 33 patients receiving emicizumab without concomitant aPCC. Of the 37 TEs, 17 (45.9%) occurred in patients with reported FVIII inhibitors, and 7 (18.9%) occurred in patients with central venous access devices (CVADs). Of the 30 TEs not related to aPCC and CVAD, 6 (20%) prompted the cessation of emicizumab.
Two cases had limited information; however, the remaining 35 TEs happened in individuals with at least 1 cardiovascular risk factor or with thrombosis risk factors. Cardiovascular risk factors included previous myocardial infarction (MI), coronary artery disease, ischemic heart disease, hypertension, hyperlipidemia, advanced age, and smoking.
Risk factors for thrombosis included sepsis/bacteremia, device use, hepatitis C, and coinciding injury. Four TMAs and 2 TEs occurred in 6 patients receiving emicizumab with aPCC, therefore, all TMA cases in this study occurred with concomitant use of emicizumab and aPCC.
In total, 4 TEs caused patient death, including 2 MIs in patients with complex comorbidities and 2 disseminated intravascular coagulation events in patients of advanced age (>70 years) who had pneumonia. Twenty of the 31 reported TEs (64.5%) resolved with most requiring no change to emicizumab treatment due to the event.
“The risk-benefit profile of emicizumab remains unchanged,” the authors concluded.
Howard M, McKinley D, Sanabria F, Ko RH, Nissen F. 3186 Evaluation of the safety of Emicizumab prophylaxis in persons with hemophilia A: an updated summary of thrombotic events and thrombotic microangiopathies. Poster presented at: 63rd American Society for Hematology Annual Meeting & Exposition: December 13, 2021; Atlanta, GA.