Ofatumumab for multirelapsing membranous nephropathy complicated by rituximab-induced serum-sickness

Podestà, Manuel Alfredo; Ruggiero, Barbara; Remuzzi, Giuseppe; Ruggenenti, Piero

doi:10.1136/bcr-2019-232896

Cited by 38 publications

(48 citation statements)

References 36 publications

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“…New anti-CD20 humanized antibodies are now on the market. They have several advantages over rituximab such as low risk of immunization against the monoclonal antibody and prolonged B-cell depletion.Several case reports and case series have shown that these new antibodies (ofatumumab, obinutuzumab, ocrelizumab) could be effective in refractory or multi-relapsing MN as well as in the patients treated with rituximab that developed serum sickness [ 23 , 24 , 25 , 26 ]. Since in about 30% to 40% of patients, rituximab fails to induce remission of MN and relapses are frequent, these more potent biotherapies will most likely take a substantial part in severe forms of MN in a near future.…”

Section: Perspectivesmentioning

confidence: 99%

Advances in Membranous Nephropathy

Ronco

Plaisier

Dębiec

2021

JCM

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Membranous nephropathy (MN) is a rare auto-immune disease where the glomerulus is targeted by circulating auto-antibodies mostly against podocyte antigens, which results in the formation of electron-dense immune complexes, activation of complement and massive proteinuria. MN is the most common cause of nephrotic syndrome in adults leading to severe thrombotic complications and kidney failure. This review is focused on the recent therapeutic and pathophysiological advances that occurred in the last two years. For a long time, we were lacking a head-to-head comparison between cyclophosphamide considered as the gold standard therapy and other medications, notably rituximab. Substantial progress has been achieved owing to three randomized controlled trials. MENTOR (Membranous Nephropathy Trial of Rituximab) and STARMEN (Sequential Therapy with Tacrolimus and Rituximab in Primary Membranous Nephropathy) conclusively established that calcineurin inhibitor-based regimens are slower to result in an immunologic response than rituximab or cyclophosphamide, achieve fewer complete clinical remissions, and are less likely to maintainremission. Rituximab Versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy (RI-CYCLO) suggested that competition between cyclophosphamide and rituximab remains open. Given the technological leapcombining laser microdissection of glomeruli and mass spectrometry of solubilized digested proteins, four “new antigens” were discovered including NELL-1 and Semaphorin 3B in so-called primary MN, and exostosins 1 and 2 and NCAM 1 in lupus MN. NELL-1 is associated with about 8% of primary MN and is characterized by segmental immune deposits and frequent association with cancer (30%). Semaphorin 3B-associated MN usually occurs in children, often below the age of two years, where it is the main antigen, representing about 16% of non-lupus MN in childhood. Exostosins 1/2 and NCAM 1 are associated with 30% and 6% of lupus MN, respectively. Exostosins 1/2 (EXT1/2) staining is associated with a low rate of end-stage kidney disease (ESKD) even in mixed classes III/IV+V. These findings already lead to revisiting the diagnostic and therapeutic algorithms toward more personalized medicine.

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Section: Perspectivesmentioning

confidence: 99%

Advances in Membranous Nephropathy

Ronco

Plaisier

Dębiec

2021

JCM

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“…On subsequent relapse, ofatumumab (300 mg) achieved remission of the NS, without significant side effects. Overall, this patient received 3 times ofatumumab in approximately four years interval, and one year after the second injection he experienced viral enteritis with high-grade fever and finally with the third infusion of ofatumumab, partial remission was achieved (13).…”

Section: Discussionmentioning

confidence: 92%

“…One patient had post-transplant recurrent FSGS (6,11). Gastrointestinal complications such as nausea, vomiting, and abdominal pain were reported in some studies (1,13,16).…”

Section: N 5 Study Selectionmentioning

confidence: 95%

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A Systematic Review of Efficacy and Safety of Ofatumumab Therapy in Children With Difficult-to-treat Nephrotic Syndrome

et al. 2020

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Context: Different studies have been done so far on drug safety and efficacy in children with refractory nephrotic syndrome (NS). Ofatumumab might be an effective drug for this syndrome; however, the long-term effects and cost-effectiveness of ofatumumab treatment have not been comprehensively assessed. Objectives: This study aims to perform a systematic review of the efficacy and safety of ofatumumab in children with difficult-to-treat NS. Study Selection: An electronic literature search was conducted to identify appropriate studies. The search key terms were as follows: (“nephrotic syndrome” OR “minimal change disease” OR “focal segmental glomerulosclerosis” OR “membranous”) AND (“Ofatumumab” or “CD20” or “Arzerra” or “HuMax-CD20”). Data Extraction: Data were extracted from the articles according to the selection criteria by two independent reviewers. Results: A total of 83 potentially relevant articles were identified. Thirty-two articles were removed due to duplication. Then 26 more articles were excluded because they were book sections and review papers and therefore not relevant. Another 14 items were removed after reviewing the full text of selected papers because the topics did not fit our study subject. Finally, 11 studies were selected in our systematic review. The benchmark considered to assess the efficacy of ofatumumab in children with nephrotic syndrome in most of the studies was a complete remission rate. Conclusions: In conclusion, our systematic review showed that ofatumumab may be an effective drug in refractory NS treatment in children and could bring down the use of steroids and immunosuppressants. However, further large randomized trials are suggested.

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“…Two patients had persistent nephrotic-range proteinuria while one had partial remission. In a more recent case report [21] on an 18-year-old boy with PLA2R-related MN refractory to steroids/CSA, remissions were achieved with RTX. The seventh dose of RTX was complicated by infusion-related reaction then delayed serum-sickness, which resolved with steroids.…”

Section: Membranous Nephropathymentioning

confidence: 99%

The Use of Ofatumumab in Renal Conditions

Leow

2020

SN Compr. Clin. Med.

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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.

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Ofatumumab for multirelapsing membranous nephropathy complicated by rituximab-induced serum-sickness

Cited by 38 publications

References 36 publications

Advances in Membranous Nephropathy

Advances in Membranous Nephropathy

A Systematic Review of Efficacy and Safety of Ofatumumab Therapy in Children With Difficult-to-treat Nephrotic Syndrome

The Use of Ofatumumab in Renal Conditions

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