Rituximab in Membranous Nephropathy: Not All Studies Are Created Equal

Abstract

Many prospective studies and a recent randomized controlled trial have shown that the B-cell-depleting monoclonal antibody, rituximab, safely promotes the remission of nephrotic syndrome in approximately 65% of patients with membranous nephropathy (MN). Mechanistic studies have indicated that rituximab-induced proteinuria reduction is associated with clearance of anti-podocyte antigens phospholipase 2 receptor autoantibodies and subepithelial immune complexes, the hallmarks of the disease. A recently published study reported results which, at first sight, looked less favorable and implied that, due to a publication bias against negative results, the efficacy of rituximab in MN might be overestimated. Since patients received only one or 2 rituximab administrations, the authors suggest that when rituximab is used, higher doses and longer treatments should be considered. In this study, we highlight limitations of the study and warn against an oversimplified interpretation of the data. Though information on the optimal dose of rituximab to use in MN is still limited, available data from studies with predefined rituximab administration protocols collectively support the concept of titrating rituximab to the number of circulating B-cells that are invariably depleted after the first or second administration. Additional doses may increase the risk of adverse effects and related costs without augmenting efficacy. Importantly, underpowered studies with inconclusive results should not be confused with negative studies formally proving a neutral effect of a treatment. Until data from ad hoc designed clinical trials are available, the B-cell-driven protocol should be the preferred regimen, since it is similarly effective, but safer and more cost effective than other protocols employing multiple rituximab administrations.

Acute demyelinating neuropathy associated with rituximab treatment in a patient with relapsing nephrotic syndrome

“…Given that one does not condemn a potentially important therapy based on isolated reports [1,2,5]. The current case provides emphasis that new therapies require close clinical monitoring and strict indications.…”

“…This patient presented 5 month history of peripheral swelling and microscopic haematuria. Laboratory tests showed normal creatinine (0.8 mg/dl), heavy proteinuria (6 g/daily), and negative screening for secondary causes of MN [1]. Renal biopsy showed diffuse thickening of glomerular capillary basement membrane with basement membrane spikes and subepithelial granular deposits of IgG and C 3 on immunofluorescence.…”

“…To the Editor, Rituximab, the monoclonal antibody directed against CD20, represents ideal treatment of both membranous nephropathy (MN) and demyelinating neuropathy associated with antibodies to myelin-associated glycoprotein (MAG) [1,2]. Clinical efficacy, safety, and modulating effects on normal and malignant pre-B and mature B cells have been reported [1,2].…”

“…Clinical efficacy, safety, and modulating effects on normal and malignant pre-B and mature B cells have been reported [1,2]. We encountered a 63-year-old woman who experienced acute onset of demyelinating polyneuropathy (AIDP) after rituximab infusions to treat her nephrotic syndrome (NS) [1].…”

“…Renal biopsy showed diffuse thickening of glomerular capillary basement membrane with basement membrane spikes and subepithelial granular deposits of IgG and C 3 on immunofluorescence. She had circulating anti-phospholipase A 2 receptor (PLA 2 R) antibodies [1]. Patient received intravenous methylprednisolone (10 mg/kg of bw daily for 3 days) followed by tapering oral prednisone and cyclophosphamide (100 mg daily).…”