Dataset Information

Randomized Trial on the Effect of an Oral Spleen Tyrosine Kinase Inhibitor in the Treatment of IgA Nephropathy.

ABSTRACT:

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.

SUBMITTER: Tam FWK

PROVIDER: S-EPMC10719605 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Randomized Trial on the Effect of an Oral Spleen Tyrosine Kinase Inhibitor in the Treatment of IgA Nephropathy.

Tam Frederick W K FWK Tumlin James J Barratt Jonathan J Rovin Brad H BH Roberts Ian S D ISD Roufosse Candice C Cook H Terence HT Bhangal Gurjeet G Brown Alison L AL Busch Martin M Dudhiya Fayaz F Duliege Anne-Marie AM Fraser Donald J DJ Gale Daniel P DP Huang Chiu-Ching CC Lai Ping-Chin PC Lee Meng M Masuda Esteban S ES McAdoo Stephen P SP Rosenkranz Alexander R AR Sommerer Claudia C Sunder-Plassmann Gere G Szeto Cheuk-Chun CC Tang Sydney C W SCW Williamson Don E DE Willcocks Lisa L Vielhauer Volker V Kim Min Jeong MJ Todd Leslie L Zayed Hany H Tong-Starksen Sandra S Lafayette Richard R

Kidney international reports 20230930 12

<h4>Introduction</h4>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.<h4>Methods</h4>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 2 ...[more]

PMID: 38106605

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Dataset Information

Randomized Trial on the Effect of an Oral Spleen Tyrosine Kinase Inhibitor in the Treatment of IgA Nephropathy.

Introduction

Methods

Results

Conclusions

Publications

Randomized Trial on the Effect of an Oral Spleen Tyrosine Kinase Inhibitor in the Treatment of IgA Nephropathy.

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