Glomerular diseases are probably one of the most satisfying subspecialities of nephrology.
As we step into the new year of 2023, we eagerly look forward to all that can help us fight glomerular diseases better and faster and with maximum efficiency. We review some of the late-breaking trials from Kidney Week 2022, which will help us keep our eyes open for the real action in the world of glomerulonephritis.
Roccatello et al. (1) have aimed to study the safety and efficacy of an intensified B-cell depletion induction therapy (IBCDT) in lupus nephritis (LN). The proposed regimen was comprised of weekly rituximab (375 mg/m2) and two more doses after 1 and 2 months. It also included two infusions of 10 mg/kg cyclophosphamide (three methylprednisolone pulses), followed by oral prednisone (tapered to 5 mg/day by the third month) without an immunosuppressive maintenance regimen, compared with standard of care in biopsy-proven LN. At the end of 1 year, they found that the IBCDT was as efficacious as the conventional therapy of LN (with the advantage of not requiring any further maintenance therapy and much lower doses of steroids compared with conventional therapy). Now, that seems to be a promising, new regimen given the fact that patients with lupus have a very long and intense amount of immunosuppression.
The Safety and Efficacy Study of VIS649 for IgA [immunoglobulin A] Nephropathy (NCT04287985) is a global, multicentric, randomized controlled trial that has evaluated monthly intravenous sibeprenlimab (a humanized IgG2 monoclonal antibody that prevents the A proliferation-inducing ligand) in IgA nephropathy vs. placebo. In this interim analysis of a phase 2 study, Kooienga et al. (2) have demonstrated an acceptable tolerability and safety profile with a significant reduction in the urinary protein excretion and stabilization of the estimated glomerular filtration rate when compared with the placebo at 9 months of study. Depending on the final results, this study marks an intense attack on the pathobiology of IgA nephropathy treatment.
Barratt et al. (3) explored the use of cemdisiran, a subcutaneously administered, investigational RNA interference therapeutic that completely inhibits the hepatic production of C5 of the complement cascade for the therapy of patients with IgA nephropathy with proteinuria greater than 1 g/day. This phase 2, randomized, double-blinded, placebo-controlled trial (A Study of Cemdisiran in Adults with Immunoglobulin A Nephropathy [IgAN]; NCT03841448) in adults has shown a promising result in reduction of proteinuria at week 32 of the study with an acceptable safety profile, including lack of infections with encapsulated organisms.
As we await the opening of the Pandora’s box of glomerular diseases therapy, we hope that we improve our knowledge and are able to offer more precise and less toxic therapy to our patients. Keep a look out please!
Roccatello D, et al. A prospective study on long-term clinical outcomes of patients with lupus nephritis treated with an intensified B-cell depletion protocol without maintenance therapy. Kidney Week 2022. November 3, 2022. Abstract TH-PO989. https://www.asn-online.org/education/kidneyweek/2022/program-abstract.aspx?controlId=3804842
Kooienga L, et al. Interim analysis (IA) of a global phase 2 randomized controlled trial of sibeprenlimab (VIS649), an APRIL-neutralizing monoclonal antibody, in IgA nephropathy. Kidney Week 2022. November 3, 2022. Abstract TH-PO991. https://www.asn-online.org/education/kidneyweek/2022/program-abstract.aspx?controlId=3804873
Barratt J, et al. Exploratory results from the phase 2 study of cemdisiran in patients with IgA nephropathy. Kidney Week 2022. November 4, 2022. Abstract FR-OR67. https://www.asn-online.org/education/kidneyweek/2022/program-abstract.aspx?controlId=3797891