title: 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.
authors.affiliation: Arthur Bloom Haemophilia Centre, University Hospital of Wales, School of Medicine, Cardiff University, Cardiff, UK. peter.collins@wales.nhs.uk
authors.forename: Peter
authors.initials: P
authors.lastname: Collins
authors.forename: Francesco
authors.initials: F
authors.lastname: Baudo
authors.forename: Paul
authors.initials: P
authors.lastname: Knoebl
authors.forename: Hervé
authors.initials: H
authors.lastname: Lévesque
authors.forename: László
authors.initials: L
authors.lastname: Nemes
authors.forename: Fabio
authors.initials: F
authors.lastname: Pellegrini
authors.forename: Pascual
authors.initials: P
authors.lastname: Marco
authors.forename: Lilian
authors.initials: L
authors.lastname: Tengborn
authors.forename: Angela
authors.initials: A
authors.lastname: Huth-Kühne
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D001323:Autoantibodies / Q000276:immunology*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects; D005060:Europe; D005169:Factor VIII / Q000276:immunology* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006467:Hemophilia A / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D012042:Registries / Q000706:statistics & numerical data*; D000069283:Rituximab; D055502:Secondary Prevention; D013256:Steroids / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D007166:Immunosuppressive Agents; D013256:Steroids; D000069283:Rituximab; D016572:Cyclosporine; D003520:Cyclophosphamide; D005169:Factor VIII