Data show that patients who have factor VIII (FVIII) inhibitor titers of 20 or higher BU/mL took longer to achieve complete responses (CR) and had lower CR rates vs patients with lower titers.
Multicenter findings are bolstering previous reports that factor VIII (FVIII) inhibitor antibody tier is an indicator of early complete response to immunosuppressive therapy (IST) in patients with acquired hemophilia A (AHA).
Although most cases of acute bleeding can be addressed by bypassing agents, steroids—either alone or in combination with cyclophosphamide—have shown to be effective first-line IST for eradication of FVIII inhibitory antibodies.
“Although 60% to 80% of patients respond to IST, the response is sometimes delayed and so there remains a risk of fatal hemorrhage during treatment,” wrote the researchers in Clinical and Applied Thrombosis Hemostasis. “The treatment goal is to achieve rapid response without increasing risk of immunosuppression-related mortality. It is therefore important to select the appropriate initial therapy for each patient and, for this, the clinical and laboratory parameters that could predict outcome and guide treatment decisions need to be clearly identified.”
Data from the small, retrospective study of Chinese patients show that those with FVIII inhibitor titers of 20 or higher BU/mL took longer to achieve a complete response (CR) and had lower CR rates compared with patients with lower titers, making it the fourth study to show such results.
Based on the finding, the researchers emphasize that these patients should be considered for first-line steroids plus another immunosuppressant followed by steroids plus sirolimus or cyclosporine as second-line or salvage treatment.
IST was given to all 34 patients who had complete data available for review. Following treatment, 60% of the 5 patients who received only steroids, 70.8% of the 24 patients who received steroids plus cyclophosphamide, and 80% of the 5 patients who received steroids plus cyclophosphamide and rituximab responded to treatment.
Altogether, 29 patients achieved a CR, 4 (13.8%) of whom relapsed after a median of 410 days. Following salvage therapy, 2 of these patients achieved a CR, although both relapsed again, with 1 patient receiving a diagnosis of mucinous adenocarcinoma of the lung and the other, with prostate cancer.
“Thus, 2 of the 4 patients (50%) who relapsed in our cohort were diagnosed with malignant tumors after recurrence, which suggests that evidence of tumor, autoimmune disease, and other etiologies should be sought in patients who relapse,” described the researchers. “[Fourteen of 34] (41.2%) patients in our cohort experienced treatment-related side effects, possibly related to the higher proportion of patients receiving steroids combined with cyclophosphamide. However, there was no incidence of death due to infection, sepsis, or neutropenia, which may be related to the younger median age of our cohort.”
Among the 2 deaths reported in the study, both were a result of refractory bleeding.There were no variables that had a significant impact on overall survival.
The study investigators concluded that having an FVIII inhibitory title level of at least 20 BU/mL has potential to be predictive of “time to CR in patients with AHA treated with IST.”
Liu Y, Ruan X, Lei P, et al. Acquired hemophilia A: a retrospective multicenter analysis of 42 patients. Clin Appl Thromb/Hemost. Published online January 18, 2023. doi:10.1177/10760296221151165