Emicizumab, an FVIII-mimetic bispecific antibody, proved to be an effective and safe outpatient prophylaxis option in patients with acquired hemophilia A (AHA), according to results from a study presented at the 2021 ASH Annual Meeting. Lead author Jacqueline N. Poston, MD, shared the findings.
The investigators queried 87 U.S. hematologists on their use of emicizumab for AHA; 32 responded with their experiences. Ten hematologist respondents reported 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 the queried hemophilia treatment centers. Forty patients with AHA were treated with off-label emicizumab. 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. 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% (range = <1%-28%). In addition, the median maximum inhibitor titer was 54 BU/mL. Nearly 80% of patients were receiving immunosuppression before starting emicizumab. The most common form of immunosuppression was glucocorticoids (67%), followed by 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. 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.
The researchers reported that nearly all patients (95%) tolerated the study drug without complications. One patient experienced deep vein thrombosis (DVT) during maintenance with emicizumab 3 mg/kg every other week. 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. They added that additional safety and dosing data are needed to clarify the role of emicizumab in this setting.
