Development of anti-rituximab antibodies in rituximab-treated patients: Related parameters & consequences

The utilization of the monoclonal antibodies (mAbs) as therapeutic agents is one of the most favourable fields in immunotherapy. The immunogenicity of mAbs is one of the major parameters that may restrict their therapeutic and diagnostic applications. Rituximab, a chimeric mAb against CD20, is attached to the B-cell membrane-linked CD20 and is used to treat some B-cell-related malignancies, a number of autoantibody-mediated autoimmune disorders and improvement of graft survival. The risk of anti-rituximab antibody (ARA) development and ARA-related adverse events are low in rituximab-treated patients with lymphoma. No important association was reported between the ARA positivity and drug levels, and drug efficacy in rituximab-treated patients with lymphoma. The patients with autoimmune disorders exhibit greater risk of ARA development and ARA-related adverse events. In autoimmune diseases, ARA positivity may have no significant impact on either the drug level or its efficacy, (i.e.), it may reduce drug levels without influencing drug efficacy and, vice versa, or may reduce both drug level as well as its efficacy. The characterization of the parameters affecting the production of ARA can be used to design strategies to reduce the immunogenicity of mAb and promote its efficacy in humans. In this review, the host and therapeutic programme-related parameters affecting the development of the ARA have been discussed to suggest novel insights to reduce ARA-associated adverse events and enhance the drug efficacy.