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@article{Tam:2023:10.1016/j.ekir.2023.09.024,
author = {Tam, FWK and Tumlin, J and Barratt, J and Rovin, BH and Roberts, ISD and Roufosse, C and Cook, HT and Bhangal, G and Brown, AL and Busch, M and Dudhiya, F and Duliege, A-M and Fraser, DJ and Gale, DP and Huang, C-C and Lai, P-C and Lee, M and Masuda, ES and McAdoo, SP and Rosenkranz, AR and Sommerer, C and Sunder-Plassmann, G and Szeto, C-C and Tang, SCW and Williamson, DE and Willcocks, L and Vielhauer, V and Kim, MJ and Todd, L and Zayed, H and Tong-Starksen, S and Lafayette, R},
doi = {10.1016/j.ekir.2023.09.024},
journal = {Kidney International Reports},
pages = {2546--2556},
title = {Randomized trial on the effect of an oral spleen tyrosine kinase inhibitor in the treatment of IgA nephropathy},
url = {http://dx.doi.org/10.1016/j.ekir.2023.09.024},
volume = {8},
year = {2023}
}

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TY  - JOUR
AB  - IntroductionWe 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.MethodsThis 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.ResultsAlthough 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).ConclusionsThere 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.
AU  - Tam,FWK
AU  - Tumlin,J
AU  - Barratt,J
AU  - Rovin,BH
AU  - Roberts,ISD
AU  - Roufosse,C
AU  - Cook,HT
AU  - Bhangal,G
AU  - Brown,AL
AU  - Busch,M
AU  - Dudhiya,F
AU  - Duliege,A-M
AU  - Fraser,DJ
AU  - Gale,DP
AU  - Huang,C-C
AU  - Lai,P-C
AU  - Lee,M
AU  - Masuda,ES
AU  - McAdoo,SP
AU  - Rosenkranz,AR
AU  - Sommerer,C
AU  - Sunder-Plassmann,G
AU  - Szeto,C-C
AU  - Tang,SCW
AU  - Williamson,DE
AU  - Willcocks,L
AU  - Vielhauer,V
AU  - Kim,MJ
AU  - Todd,L
AU  - Zayed,H
AU  - Tong-Starksen,S
AU  - Lafayette,R
DO  - 10.1016/j.ekir.2023.09.024
EP  - 2556
PY  - 2023///
SN  - 2468-0249
SP  - 2546
TI  - Randomized trial on the effect of an oral spleen tyrosine kinase inhibitor in the treatment of IgA nephropathy
T2  - Kidney International Reports
UR  - http://dx.doi.org/10.1016/j.ekir.2023.09.024
UR  - http://hdl.handle.net/10044/1/107254
VL  - 8
ER  -

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