Repurposing of rituximab biosimilars to treat B cell mediated autoimmune diseases

Rituximab, the first monoclonal antibody approved for the treatment of lymphoma, eventually became one of the most popular and versatile drugs ever in terms of clinical application and revenue. Since its patent expiration, and consequently, the loss of exclusivity of the original biologic, its repur...

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Bibliographic Details
Published in:The FASEB journal 2024-03, Vol.38 (5), p.e23536-n/a
Main Authors: Mostkowska, Agata, Rousseau, Guy, Raynal, Noël J‐M
Format: Article
Language:English
Subjects:
autoimmune diseases
Autoimmune Diseases - drug therapy
biological therapy
Biosimilar Pharmaceuticals - therapeutic use
biosimilars
Drug Repositioning
drug repurposing
Humans
immunotherapy
monoclonal antibodies
Off-Label Use
Rare Diseases
rituximab
Rituximab - therapeutic use
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Summary:Rituximab, the first monoclonal antibody approved for the treatment of lymphoma, eventually became one of the most popular and versatile drugs ever in terms of clinical application and revenue. Since its patent expiration, and consequently, the loss of exclusivity of the original biologic, its repurposing as an off‐label drug has increased dramatically, propelled by the development and commercialization of its many biosimilars. Currently, rituximab is prescribed worldwide to treat a vast range of autoimmune diseases mediated by B cells. Here, we present a comprehensive overview of rituximab repurposing in 115 autoimmune diseases across 17 medical specialties, sourced from over 1530 publications. Our work highlights the extent of its off‐label use and clinical benefits, underlining the success of rituximab repurposing for both common and orphan immune‐related diseases. We discuss the scientific mechanism associated with its clinical efficacy and provide additional indications for which rituximab could be investigated. Our study presents rituximab as a flagship example of drug repurposing owing to its central role in targeting cluster of differentiate 20 positive (CD20) B cells in 115 autoimmune diseases. B cell functions include: (A) acting as antigen‐presenting cells (APCs) through B‐cell antigen receptors (BCRs), (B) interacting with T cells via the major histocompatibility complex class II (MHC II) and T‐cell receptors (TCRs), (C) producing autoantibodies, and (D) producing inflammatory cytokines. When aberrant, they employ these mechanisms against self, fostering autoimmunity. By depleting CD20+ B cells, rituximab rewires the immune system such that self‐proteins are no longer perceived as foreign, benefitting over a hundred autoimmune disorders in 17 medical disciplines.
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.202302259RR