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Ferrata Storti Foundation
Haematologica 2019 Volume 104(6):1124-1135
Rituximab in the treatment of immune thrombocytopenia: what is the role of this agent in 2019?
Elisa Lucchini,1 Francesco Zaja1 and James Bussel2
1SC Ematologia, Azienda Sanitaria Universitaria Integrata Trieste, Italy and 2Weill Cornell Medicine, New York, NY, USA
ABSTRACT
The use of rituximab for the treatment of immune thrombocytopenia was greeted enthusiastically: it led to up to 60% response rates, mak- ing it, nearly 20 years ago, the main alternative to splenectomy, with far fewer side effects. However, long-term follow-up data showed that only 20-30% of patients maintained the remission. No significant changes have been registered using different dose schedules and timing of administration, while the combination with other drugs seemed promising. Higher response rates have been observed in young women before the chronic phase, but apart from that, other clinical factors or biomarkers predictive of response are still lacking. In this review we examine the historical and cur- rent role of rituximab in the management of immune thrombocytopenia, 20 years after its first use for the treatment of autoimmune diseases.
Introduction
Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder due to a variable combination of increased platelet destruction and impaired platelet production, as a consequence of defects in central and/or peripheral immune tolerance which allow the escape of autoreactive lymphocytes.1–3 B cells have a well-established role in the pathogenesis of the disease, as the source of anti- bodies directed against platelet-surface glycoproteins.4–6
Rituximab, a monoclonal antibody directed against CD20, a membrane glyco- protein expressed on the surface of B cells, was introduced for the treatment of B- cell lymphomas towards the end of the 1980s.7
Binding to an antigen that is only expressed on mature B cells, rituximab leads to a fast and deep, but reversible B-cell depletion.8 The transience of the B-cell deple- tion and the low toxicity profile represented the rationale for its use in the treat- ment of autoimmune conditions, especially those in which B-cell activity was con- sidered the main pathogenic mechanism, such as ITP. Many studies have been car- ried out in this field: in monotherapy, with different dose schedules and in combi- nation with other drugs, proving its efficacy, although some differences exist across certain studies.
Rituximab has also been explored in a number of other autoimmune auto-anti- body-mediated diseases such as systemic lupus erythematosus,9 rheumatoid arthri- tis,10 autoimmune hemolytic anemia,11 type II mixed cryoglobulinemia,12 myasthe- nia gravis,13 multiple sclerosis,14 thrombotic thrombocytopenic purpura,15 Sjogren syndrome,16 pemphigus17 and others. Despite these extensive investigations, autoimmune conditions for which rituximab is licensed by the Food and Drug Administration and the European Medicines Agency are rheumatoid arthritis and ANCA-associated vasculitis.
In this review, we discuss the development and current role of rituximab in the management of ITP.
Pathophysiology of immune thrombocytopenia
The milestone role of autoantibodies in the pathogenesis of ITP was first report- ed in 1951 by Harrington et al., who showed that the infusion of plasma from ITP
Correspondence:
FRANCESCO ZAJA
francesco.zaja@asuits.sanita.fvg.it
Received: February 28, 2019. Accepted: May 9, 2019. Pre-published: May 24, 2019.
doi:10.3324/haematol.2019.218883
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/6/1124
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