Immune tolerance with rituximab in congenital haemophilia with inhibitors: a systematic literature review based on individual patients' analysis

Haemophilia. 2008 Sep;14(5):903-12. doi: 10.1111/j.1365-2516.2008.01839.x. Epub 2008 Jul 28.

Abstract

Rituximab, a monoclonal antibody against the pan B-cell antigen CD20, has been successfully used in both adults and children for the management of malignant and non-malignant immune-mediated disorders including acquired haemophilia. On the basis of this positive experience, a number of investigators have recently used this agent in patients with congenital haemophilia and inhibitors refractory to first-line treatments. After a careful electronic and hand search, we have collected 29 studies that included 49 cases. A durable complete remission was obtained in 53% of the cases and no severe adverse events related to rituximab were recorded. A multivariate analysis applied to individual patients' data identified the diagnosis of a mild/moderate haemophilia and the concomitant treatment with factor VIII concentrates and immunosuppression agents as covariates associated with an increased response to rituximab. Large prospective randomized studies with an adequate follow-up are needed to confirm these preliminary findings.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Murine-Derived
  • Child
  • Child, Preschool
  • Factor VIII / antagonists & inhibitors
  • Factor VIII / immunology
  • Hemophilia A / drug therapy
  • Hemophilia A / immunology*
  • Humans
  • Immune Tolerance / drug effects*
  • Immunosuppressive Agents / therapeutic use*
  • Infant
  • Isoantibodies / blood
  • Male
  • Middle Aged
  • Rituximab
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Immunosuppressive Agents
  • Isoantibodies
  • Rituximab
  • Factor VIII