Browse by author
Lookup NU author(s): Alison Brown
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2023 International Society of Nephrology. Introduction: We reported increased spleen tyrosine kinase (SYK) expression in kidney biopsies of patients with IgA nephropathy (IgAN) and that inhibition of SYK reduces inflammatory cytokines production from IgA stimulated mesangial cells. Methods: This study was a double-blind, randomized, placebo-controlled phase 2 trial of fostamatinib (an oral SYK inhibitor) in 76 patients with IgAN. Patients were randomized to receive placebo, fostamatinib at 100 mg or 150 mg twice daily for 24 weeks on top of maximum tolerated dose of renin-angiotensin system inhibitors. The primary end point was reduction of proteinuria. Secondary end points included change from baseline in estimated glomerular filtration rate (eGFR) and kidney histology. Results: Although we could not detect significant reduction in proteinuria with fostamatinib overall, in a predetermined subgroup analysis, there was a trend for dose-dependent reduction in median proteinuria (from baseline to 24 weeks by 14%, 27%, and 36% in the placebo, fostamatinib 100 mg, and 150 mg groups, respectively) in patients with baseline urinary protein-to-creatinine ratios (UPCR) more than 1000 mg/g. Kidney function (eGFR) remained stable in all groups. Fostamatinib was well-tolerated. Side effects included diarrhea, hypertension, and increased liver enzymes. Thirty-nine patients underwent repeat biopsy showing reductions in SYK staining associated with therapy at low dose (−1.5 vs. 1.7 SYK+ cells/glomerulus in the placebo group, P < 0.05). Conclusions: There was a trend toward reduction in proteinuria with fostamatinib in a predefined analysis of high risk patients with IgAN despite maximal care, as defined by baseline UPCR greater than 1000 mg/g. Further study may be warranted.
Author(s): Tam FWK, Tumlin J, Barratt J, Rovin BH, Roberts ISD, Roufosse C, Cook HT, Bhangal G, Brown AL, Busch M, Dudhiya F, Duliege A-M, Fraser DJ, Gale DP, Huang C-C, Lai P-C, Lee M, Masuda ES, McAdoo SP, Rosenkranz AR, Sommerer C, Sunder-Plassmann G, Szeto C-C, Tang SCW, Williamson DE, Willcocks L, Vielhauer V, Kim MJ, Todd L, Zayed H, Tong-Starksen S, Lafayette R
Publication type: Article
Publication status: Published
Journal: Kidney International Reports
Year: 2023
Volume: 8
Issue: 12
Pages: 2546-2556
Print publication date: 01/12/2023
Online publication date: 29/09/2023
Acceptance date: 18/09/2023
Date deposited: 21/11/2023
ISSN (electronic): 2468-0249
Publisher: Elsevier Inc.
URL: https://doi.org/10.1016/j.ekir.2023.09.024
DOI: 10.1016/j.ekir.2023.09.024
Data Access Statement: Rigel Pharmaceuticals, Inc. is committed to data transparency and will consider data sharing requests on a case-by-case basis. Additionally, Rigel Pharmaceuticals, Inc. will provide the study protocol as well as post results on ClinicalTrials.gov as required.
Altmetrics provided by Altmetric
