The Use of Ofatumumab in Renal Conditions
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MEDICINE
The Use of Ofatumumab in Renal Conditions Esther Huimin Leow 1 Accepted: 7 September 2020 # Springer Nature Switzerland AG 2020
Abstract Ofatumumab is a fully humanized monoclonal antibody against CD20. It has been initially used against hematological malignancies but now has been reported widely for autoimmune or rheumatological (e.g., rheumatoid arthritis, multiple sclerosis) and renal conditions. Over the past decade, since the first report on its use in rituximab-resistant nephrotic syndrome, there have been many more centers describing their experience with ofatumumab. Due to it being relatively new, the optimal dosing of ofatumumab for renal conditions has not been established, especially in children, and studies so far have been mainly case reports or case series. Large-scale, multi-center prospective studies are required to establish the appropriate dosing and investigate adverse reactions of ofatumumab. Reported studies on the use of ofatumumab in renal conditions and reported or potential adverse reactions are discussed in this review. Keywords Ofatumumab . Nephrotic syndrome . Lupus nephritis . Renal transplant . IgA vasculitis with nephropathy
Introduction Ofatumumab (OFA) is a fully humanized monoclonal antibody against CD20 antigen. CD20 is situated on the surface of pre-B cells maturing to memory B cells; therefore, all B cell subsets, except precursors and plasma cells, express the CD20 antigen [1]. CD20 is involved in B cell maturation and calcium signaling. OFA depletes B cells by directly activating signaling pathways resulting in apoptosis or by means of host immune system components, such as complement system or cells bearing Fc receptor, resulting in cytotoxic response (antibody-dependent cellular cytotoxicity). In primary focal segmental glomerulosclerosis (FSGS), it has been hypothesized that the activity and/or secretion of a circulating permeability factor is B cell related, hence the role of anti-CD20 antibodies. CD20 is a good target because of its high content, limited shedding compared with other pan-B markers and the lack of soluble form which would compete for antibody binding. In addition, OFA exerts cytotoxic effect on peripheral B cells
This article is part of the Topical Collection on Medicine * Esther Huimin Leow [email protected] 1
Paediatric Nephrology, KK Women’s and Children’s Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore
without affecting the regeneration from stem cells because it is not on the immature B cells residing in the bone marrow [2].
How Ofatumumab Is Different from Rituximab and Indications for Ofatumumab After the Use of Rituximab OFA recognizes an epitope located more proximally to the cell membrane [3], has greater binding avidity, and dissociates slower than rituximab (RTX). In vitro studies have suggested that OFA is a better inducer of antibody-dependent cellular cytotoxicity (ADCC) [4] and complement-dependent cytotoxicity (CDC) [5, 6] than RTX. RTX is a chimeric mouse/human monoclonal antibody against CD20, w
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