A child with semaphorin 3b-associated membranous nephropathy effectively treated with obinutuzumab after rituximab resistance

Conversano, Ester; Dębiec, Hanna; Colucci, Manuela; Emma, Francesco; Ronco, Pierre; Vivarelli, Marina

doi:10.1007/s00467-023-06085-8

Cited by 12 publications

(4 citation statements)

References 7 publications

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“…The decision to switch to obinutuzumab was based on the fact that, although both rituximab and obinutuzumab bind to the CD20 antigen on B cells, their mechanisms of action and side effects differ slightly due to structural differences and interactions with the immune system. Obinutuzumab, a humanized type II anti-CD20 monoclonal antibody (Basu et al, 2022), has been found to be effective in treating refractory PLA2R-related MN that does not respond to prednisolone, cyclosporine, cyclophosphamide, or rituximab (Sethi et al, 2020;Naik et al, 2023;Conversano et al, 2024). Compared to rituximab, obinutuzumab is a more potent inducer of antibody-dependent cell-mediated cytotoxicity (ADCC) and direct cell death (DCD).…”

Section: Discussionmentioning

confidence: 99%

Case report: One case of refractory membranous nephropathy with hypokalemia after rituximab infusion was switched to obinutuzumab without recurrence of hypokalemia

Zhang,

Sun,

Gao

et al. 2024

Front. Pharmacol.

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Rituximab (RTX) is a monoclonal antibody commonly used to treat PLA2R-associated membranous nephropathy (MN). This report presents a case of refractory MN in a patient who experienced severe hypokalemia, a rare but clinically significant condition, after the 5th RTX infusion. Clinicians should be aware of the potential for hypokalemia and its management during or after RTX infusion. After the onset of hypokalemia, the patient received treatment with obinutuzumab and achieved partial remission of renal disease without experiencing further hypokalemia. Obinutuzumab may be a viable alternative therapy for refractory membranous nephropathy that develops side effects after rituximab therapy or is refractory to it, but further studies are necessary to determine its efficacy and safety.

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Section: Discussionmentioning

confidence: 99%

Case report: One case of refractory membranous nephropathy with hypokalemia after rituximab infusion was switched to obinutuzumab without recurrence of hypokalemia

Zhang,

Sun,

Gao

et al. 2024

Front. Pharmacol.

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“…In rituximab-resistant cases, fully humanized and more potent anti-CD20 agents such as obinituzumab and ofatumumab can be utilized, as discussed below. 98 - 104 …”

Section: Rituximabmentioning

confidence: 99%

“…In cases facing rituximab resistance and failure to achieve full B-cell depletion, more potent anti-CD20 agents such as obinutuzumab can be utilized, given their success in refractory MN. 98 , 99 , 101 - 104 CNIs should be reserved only for intolerance to or unavailability of other agents, given their inferiority and higher risk of relapse. Future therapies might expand available options for MN patients with high risk.…”

Section: Treatment In Mn With Kidney Dysfunctionmentioning

confidence: 99%

“… 112 Ofatumumab has a binding site for C1q and exhibits a stronger complement-mediated cytotoxicity. 97 Reflecting their potential, both obinutuzumab 98 , 99 , 101 - 103 and ofatumumab 104 showed efficacy in refractory MN and nephrotic syndrome following a potent and prolonged B-cell depletion. At present, there are two ongoing trials with obinutuzumab in MN (NCT04629248, NCT05050214), the latter is investigating its efficacy in rituximab-resistant patients [ Table 2 ].…”

Section: Emerging Therapiesmentioning

confidence: 99%

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An Updated Review of Membranous Nephropathy

Efe,

So,

Anandh

et al. 2024

IJN

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Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults. The discovery of phospholipase A2 receptor (PLA2R) as a target antigen has led to a paradigm shift in the understanding and management of MN. At present, serum PLA2R antibodies are used for diagnosis, prognostication, and guiding treatment. Now, with the discovery of more than 20 novel target antigens, antigen mapping is almost complete. The clinical association of certain antigens provides clues for clinicians, such as the association of nerve epidermal growth factor-like 1 with malignancies and indigenous medicines. Serum antibodies are detected for most target antigens, except exostosin 1 and 2 and transforming growth factor-beta receptor 3, but their clinical utility is yet to be defined. Genome-wide association studies and studies investigating environmental factors, such as air pollution, shed more light on the underpinnings of MN. The standard therapy of MN diversified from cyclical cyclophosphamide and steroids to include rituximab and calcineurin inhibitors over the past decades. Here, we provide a cutting-edge review of MN, focusing on genetics, immune system and environmental factors, novel target antigens and their clinical characteristics, and currently available and emerging novel therapies in MN.

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Ciclosporin/Prednisone/Rituximab

2024

Reactions Weekly

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A child with semaphorin 3b-associated membranous nephropathy effectively treated with obinutuzumab after rituximab resistance

Cited by 12 publications

References 7 publications

Case report: One case of refractory membranous nephropathy with hypokalemia after rituximab infusion was switched to obinutuzumab without recurrence of hypokalemia

Case report: One case of refractory membranous nephropathy with hypokalemia after rituximab infusion was switched to obinutuzumab without recurrence of hypokalemia

An Updated Review of Membranous Nephropathy

Ciclosporin/Prednisone/Rituximab

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