The FVIII-mimetic bispecific antibody emicizumab could provide effective and safe outpatient prophylaxis in patients with acquired hemophilia A (AHA), according to results of a study presented during the 2021 ASH Annual Meeting by Jacqueline N. Poston, MD, of the Larner College of Medicine at The University of Vermont in Burlington.
While emicizumab has significantly improved prophylaxis for congenital hemophilia A, Dr. Poston and colleagues noted that the role of the antibody in AHA is currently unknown. To bridge this research gap, the investigators queried 87 U.S. hematologists on their use of emicizumab for AHA. Ten hematologist respondents reported experience with using off-label emicizumab for AHA and were asked to provide de-identified data on patients with AHA treated with the antibody at their hemophilia treatment centers.
Within the past five years, 358 patients with AHA were treated at 32 of the queried hemophilia treatment centers. Among the 10 respondents who used off-label emicizumab, 40 patients with AHA were treated with the therapy. Treatment centers that did not use emicizumab for AHA had fewer AHA cases in the past five years (mean = 8 vs. 17 patients). Approximately 86% of all hemophilia treatment centers said they would consider emicizumab in AHA if safety data in the disease were available.
Respondents who used emicizumab for AHA submitted de-identified data for 24 cases of emicizumab-treated AHA. In these cases, the median age was 73 years, ranging between 34 and 87 years. Conditions typically associated with AHA included autoimmune disease, cancer, and peripartum. One patient presented with mild congenital hemophilia A and subsequently developed an autoantibody to FVIII. Additional comorbidities in the cohort included metabolic syndrome, vascular disease, prior venous thrombosis, alcoholic pancreatitis, and Alzheimer dementia.
Antiplatelet therapy and therapeutic anticoagulation were received by four and two patients, respectively, at time of diagnosis. These treatments were discontinued in all patients. Most patients (92%) presented with bleeding, including spontaneous bleeding (63%), hematuria (17%), hemarthrosis (8%), retroperitoneal (8%), gastrointestinal (GI) bleeding (8%), and subdural hematoma (4%).
The median FVIII level at diagnosis was <1% and ranged between <1% to 28%. In addition, the median maximum inhibitor titer was 54 BU/mL. Up to 79% of patients were receiving immunosuppression before starting emicizumab. Immunosuppression included glucocorticoids (67%), rituximab (54%), cyclophosphamide (17%), mycophenolate mofetil (13%), and daratumumab (4%). Adverse events with immunosuppression were reported in four patients prior to initiating emicizumab. These events included hyperglycemia (n=1), demand ischemia (n=2), and hypersensitivity to immunosuppression (n=1).
Across centers, emicizumab was mostly initiated to either improve bleeding prophylaxis strategies (n=17) or facilitate transition to outpatient management (n=15). Other reasons for starting emicizumab were to decrease immunosuppression (n=6) or to manage bleeding despite use of other hemostatic agents (n=9). The median time from diagnosis to starting emicizumab was 19 days. Doses of emicizumab varied, but most patients received a standard loading regimen frequently used in congenital hemophilia A.
Prior to starting emicizumab, the rate of severe bleeding was 58%, which decreased to 13% following treatment. A single patient had new ecchymoses following the initial loading dose, but this resolved following additional doses. Breakthrough bleeding on emicizumab maintenance was reported in three patients, including two patients who had hematuria which resolved with hemostatic agents and one patient who had severe gastrointestinal bleeding approximately four months after initiating emicizumab. The patient with severe GI bleeding required an endoscopy and hemostatic agents for management.
Nearly all patients (95%) tolerated the study drug without complications. Deep vein thrombosis (DVT) was reported in one patient during maintenance emicizumab 3 mg/kg every other week. The patient who developed DVT had no history of the condition; however, this patient was taking apixaban for atrial fibrillation until receiving a diagnosis for AHA. The patient with DVT resumed anticoagulation after the DVT, and emicizumab was held for a total of four weeks and resumed at 1.5 mg/kg every other week with no additional complications.
Of the four deaths reported at the time of the survey, two were in patients on emicizumab. There were no deaths attributed to the antibody therapy. Among the patients who survived, eight have remained on emicizumab with persistent inhibitors, and six of these patients have been off immunosuppression.
“Emicizumab could improve AHA outcomes by providing outpatient hemostatic prophylaxis with lower-intensity immunosuppression,” the researchers concluded, noting that additional safety and dosing data are needed to clarify the role of emicizumab in this setting.
The authors report no relevant conflicts of interest.
Poston JN, Al-Banaa K, von Drygalski A, et al. Emicizumab for the treatment of acquired hemophilia a: a multicenter US case series. Abstract #496. Presented at the 2021 American Society of Hematology Annual Meeting, December 12, 2021.