Combination therapy with prednisolone and low-dose rituximab appears to be effective and well-tolerated in a subset of patients with acquired haemophilia A (AHA), according to a Queensland study.
The review of 24 patients newly diagnosed with AHA at the Queensland Haemophilia Centre between 2014 and 2018 found about half the patients (54%) had an unfavourable risk stratification.
After haemostatic therapy such as recombinant FVIIa in most patients, all received immunosuppression therapy (IST) with oral steroids such as prednisolone 1 mg/kg daily.
First-line steroid monotherapy occurred in 11 patients, fixed low-dose rituximab (100 mg weekly for 4 weeks) in six patients, oral cyclophosphamide with steroids in three patients, and standard dose rituximab at 375 mg/m2 weekly for 4 weeks in four patients.
Three patients received complex multiagent IST regimens including steroids, cyclophosphamide and rituximab; intravenous immunoglobulin; and plasma exchange respectively.
A complete remission (CR) rate of 77% was achieved with first line therapy and 92% overall.
“Rituximab-based regimens were associated with shorter time to CR than steroids or cyclophosphamide (median 3.5 vs. 7.7 weeks, P= .03), and when low-dose rituximab only was compared, it appeared non-inferior in this regard (median time to CR 1.4 weeks, range 0.6-5.1 week,” the study said.
The study, published in the European Journal of Haematology, said adverse events were mostly associated with prolonged steroid use and occurred in one-third of patients.
The mortality rate was (13%) with only one of the three deaths potentially related to IST.
The study said the efficacy of low-dose rituximab was well described in other autoimmune conditions including immune thrombocytopenia, autoimmune haemolytic anaemia and ANCA vasculitis.
“Compared with standard lymphoma dosing (375 mg/m2) in these conditions, this low-dose approach is more cost-effective with an excellent safety profile, without compromising efficacy.”
“Further study is required to establish whether this has equivalent efficacy to standard dosing in AHA,” it said.
The researchers noted the recent approval of emicizumab for congenital haemophilia A may have implications for AHA.
“There are now early case studies highlighting its potential future role in reducing duration of haemostatic products and intensity of immunosuppression, but further research is required,” they said.