Standard or low-dose rituximab effective for acquired hemophilia A
Nearly all study participants achieved complete remission with combo therapies
Nearly all adults with acquired hemophilia A (AHA) safely achieved complete remission with either standard or low doses of rituximab when combined with corticosteroids and cyclophosphamide, a small study shows.
Key features of disease remission, including an increase in clotting factor levels and a reduction in inhibitor levels, were reached faster with the standard dose of rituximab than with the low dose, despite comparable efficacy and safety profiles.
The study, “Standard dose and low-dose rituximab combined with glucocorticoids and cyclophosphamide in the treatment of acquired haemophilia A,” was published in Frontiers in Immunology.
Rituximab depletes or lowers numbers of antibody-producing B-cells
AHA is an autoimmune disorder caused by the production of self-reactive antibodies, called inhibitors, that target factor VIII (FVIII), a protein essential for blood clotting. Such attacks lower FVIII activity, leaving AHA patients vulnerable to spontaneous or excessive bleeding episodes.
Treatment using corticosteroids or other immunosuppressive agents is given on an individual basis to control bleeding and reduce or eliminate the production of inhibitors that target FVIII.
Rituximab, sold as Rituxan and others, is a therapy that depletes or lowers the numbers of antibody-producing B-cells. It has been increasingly used to help clear inhibitors in AHA patients.
Because the optimal regimen for rituximab is still unclear, clinicians in China reviewed the outcomes of 11 AHA patients, six men and five women between the ages of 29 and 88, who were treated with standard or low doses of rituximab combined with cyclophosphamide (sold as Cytoxan) and corticosteroids.
To maintain blood clotting, all patients received an infusion of fresh frozen plasma and prothrombin complex. One patient with abdominal hematoma, a pooling of blood within the abdominal wall, also received a transfusion of platelets, the cell fragments that assist in blood clotting.
Seven patients received a single standard dose of rituximab (375 mg/m2), while the other four received four weekly treatments of low-dose rituximab (100 mg). Both groups also received corticosteroids and cyclophosphamide.
9 of 11 patients achieved complete remission
After treatment, nine patients (81.8%) achieved complete remission, defined as controlled bleeding, normalization of FVIII levels, and a lack of inhibitors. Six had received the standard dose and three the low dose of rituximab.
Two patients reached partial remission, meaning bleeding symptoms had eased, FVIII levels had increased by more than 50%, and inhibitors had dropped by 50%.
Despite comparable efficacy, the standard dose regimen increased FVIII activity and lowered inhibitor levels faster than the low-dose regimen.
Our retrospective analysis indicated that the standard dose rituximab or low dose rituximab combined with cyclophosphamide and corticosteroids regimen [is an] effective treatment for AHA, and with no difference in side effects.
During follow-up, three patients relapsed, as indicated by bleeding, an increase in inhibitor levels, and a decrease in FVIII activity. One had received low-dose rituximab, and two had received the standard dose. Complete remission was reestablished with rituximab combined with cyclophosphamide and glucocorticoids.
There were no differences between the two rituximab treatment groups in the levels of immune B-cells and various types of antibodies, including immunoglobulin G (IgG), IgM, and IgA.
Adverse effects of standard dose rituximab included fever, nausea, vomiting, pneumonia, and hyperglycemia, or high blood sugar levels. Patients receiving low-dose rituximab also experienced fever, pneumonia, and hyperglycemia.
“Our retrospective analysis indicated that the standard dose rituximab or low-dose rituximab combined with cyclophosphamide and corticosteroids regimen [is an] effective treatment for AHA, and with no difference in side effects,” the researchers wrote.
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