Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2)

Abstract

Acquired hemophilia A (AHA) is an autoimmune disease caused by an autoantibody to factor VIII. Patients are at risk of severe and fatal hemorrhage until the inhibitor is eradicated, and guidelines recommend immunosuppression as soon as the diagnosis has been made. The optimal immunosuppressive regimen is unclear; therefore, data from 331 patients entered into the prospective EACH2 registry were analyzed. Steroids combined with cyclophosphamide resulted in more stable complete remission (70%), defined as inhibitor undetectable, factor VIII more than 70 IU/dL and immunosuppression stopped, than steroids alone (48%) or rituximab-based regimens (59%). Propensity score-matched analysis controlling for age, sex, factor VIII level, inhibitor titer, and underlying etiology confirmed that stable remission was more likely with steroids and cyclophosphamide than steroids alone (odds ratio = 3.25; 95% CI, 1.51-6.96; P < .003). The median time to complete remission was approximately 5 weeks for steroids with or without cyclophosphamide; rituximab-based regimens required approximately twice as long. Immunoglobulin administration did not improve outcome. Second-line therapy was successful in approximately 60% of cases that failed first-line therapy. Outcome was not affected by the choice of first-line therapy. The likelihood of achieving stable remission was not affected by underlying etiology but was influenced by the presenting inhibitor titer and FVIII level.

Figure 1

Disposition of patients from the EACH2 cohort included in this analysis of immunosuppression. The figure shows the EACH2 patient cohort and describes which patient groups were included in the analysis presented here.

Figure 2

Time to negative inhibitor of propensity score-matched groups and time to complete remission of propensity score-matched groups. Survival plots of propensity score-matched groups comparing steroids alone with steroids and oral cyclophosphamide (n = 70 in each group) showing: (A) time to negative inhibitor (HR = 2.11; 95% CI, 1.38-3.21; P < .001); and (B) time to complete remission (HR = 2.36; 95% CI, 1.49-3.74; P < .001).

Figure 3

Proportion of patients surviving at final follow-up dependent on first-line immunosuppression. Kaplan-Meier plot showing the proportion of subjects (n = 287) who were alive at final follow-up dependent on first-line treatment after a median of 262 days (IQR, 66-666 days). There were no significant differences between the groups.