In the first-line treatment of acquired haemophilia A (AHA), the use of an intravenous (IV) pulse-dose immunosuppression regimen that combines cyclophosphamide, dexamethasone, and rituximab appears to result in faster remission and improved survival compared with traditional oral sequential prednisone-based regimens, according to a study applying in silico analysis.
Time to complete remission with initial treatment was 2.4 months with the pulse-dose regimen vs 7 months with the traditional sequential regimen (p<0.0001), reported senior investigator Dr Imre Bodó from Semmelweis University, Budapest, Hungary. [EHA 2026, abstract S320]
Over a 2-year follow-up, overall survival was not reached with the pulse-dose regimen as opposed to 69.3 months with the traditional sequential regimen (p<0.0001).
Other 2-year outcomes were also more favourable in the pulse-dose regimen group than in the traditional sequential regimen group. Complete remission occurred in 93.3 percent vs 54.8 percent of patients in the respective groups (p<0.001). Mortality rate was 6 percent vs 31.1 percent (p<0.001), and the percentage of patients alive at 2 years but who were not in complete remission was 0.7 percent vs 31.1 percent (p<0.001), respectively.
“AHA is a rare, life-threatening disease and considered a medical emergency,” Bodó said. “Current international guidelines recommend oral corticosteroids as first-line therapy, with or without oral cyclophosphamide, while additional agents are reserved for steroid failure.”
However, the traditional approach has been associated with high mortality rates, with prolonged steroid exposure not tolerated well by patients, Bodó explained. Current strategies to avoid toxicity of prolonged steroid exposure include delaying immunosuppression and the use of bypassing agents.
The present data, according to the investigator, “cast some doubt on the necessity of postponing causative treatment.”
Bodó added that if confirmed in a prospective trial, the findings have the potential to be practice-changing and warrant urgent consideration by the international AHA community.
In silico comparison
The study was a direct in silico comparison of the novel upfront intravenous pulse-dose immunosuppression regimen and the traditional oral sequential regimen in AHA.
Bodó and colleagues used raw data from two comparable AHA cohorts differing primarily in immunosuppressive strategy. They enhanced comparability between the two cohorts by applying inverse probability of treatment weighting using eight baseline variables: age, sex, idiopathic AHA, postpartum AHA, time from first symptom to diagnosis, baseline FVIII activity, baseline inhibitor titer, and severe bleeding at presentation.
The traditional sequential regimen group included 135 Dutch patients from the KWARK cohort who were treated with prednisolone monotherapy or in combination with cyclophosphamide or rituximab. The pulse-dose regimen group comprised 59 Hungarian and Polish patients who received the pulse-dose regimen, which consisted of upfront dexamethasone 40 mg and rituximab 100 mg once a week for 4 weeks plus cyclophosphamide 1,000 mg at weeks 1 and 4, all administered as IV pulse dose. Both cohorts had access to identical bypassing agents.
The median age was 75 years in the pulse-dose regimen group and 74 years in the traditional sequential regimen group, with males comprising 47.5 percent and 51.9 percent of the respective groups. Most patients in both groups had idiopathic AHA (71.2 percent and 64.4 percent).
Primary endpoints were overall survival and time to complete remission. Complete remission (CR) was defined as FVIII >70 IU/dL off immunosuppression.