{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:52:46Z","timestamp":1791193966851,"version":"4.1.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100031531","name":"Travere Therapeutics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100031531","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008322","name":"CSL","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008322","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Vifor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and hypothesis<\/jats:title>\n                    <jats:p>Sparsentan, a non-immunosuppressive, dual endothelin angiotensin receptor antagonist (DEARA), and sodium\u2013glucose cotransporter-2 inhibitors (SGLT2is) reduce proteinuria in patients with immunoglobulin A nephropathy (IgAN). We report the safety and efficacy of sparsentan combined with SGLT2is in patients with IgAN in the SPARTACUS trial and a substudy in the PROTECT open-label extension (OLE).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>SPARTACUS (NCT05856760) was a phase 2, open-label trial in which patients had renin\u2013angiotensin system inhibitors (RASi) replaced with sparsentan while continuing stable SGLT2i. In the PROTECT (NCT03762850) OLE substudy, patients receiving sparsentan were randomized 1:1 to add SGLT2i or continue sparsentan alone for 12 weeks; afterward, all could receive 24 weeks of sparsentan + SGLT2i combination therapy. Endpoints in both studies included change in proteinuria and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In SPARTACUS, 48 patients were enrolled (mean [SD] age, 48.9 [13.9] y; 58% male); 39 completed treatment. Replacement of RASi with sparsentan while on stable SGLT2i led to rapid urine albumin-to-creatinine ratio reductions sustained through Week 24 (least-squares mean [95% confidence interval, CI], \u221255.8% [\u221265.8% to \u221242.8%]). In the PROTECT OLE substudy, 63 patients enrolled and completed the 12-week randomized treatment (sparsentan + SGLT2i [n\u00a0=\u00a032] vs. sparsentan alone [n\u00a0=\u00a031]: mean [SD] age, 51.4 [13.4] y vs. 50.6 [11.1] y; male 81%\u00a0vs. 68%, respectively); 54 completed 24 weeks of sparsentan\u00a0+\u00a0SGLT2i. At Week 12, significant relative reductions occurred in the urine protein-to-creatinine ratio (least-squares mean [95% CI]) with sparsentan\u00a0+\u00a0SGLT2i (\u221211.1% [\u221226.3% to 7.3%]) vs. sparsentan alone (17.7% [\u22122.4% to 42.1%]) (ratio [95% CI], 0.75 [0.58 to 0.98]; P\u00a0&amp;lt;\u00a0.05). Few treatment-related adverse events were severe or serious or led to discontinuation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In patients with IgAN, replacing RASi with sparsentan while on stable SGLT2i resulted in marked reductions in albuminuria. Adding SGLT2i to stable sparsentan resulted in modest further reductions in proteinuria. Sparsentan combined with SGLT2i was well tolerated, with no unexpected safety signals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ndt\/gfag211","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T11:50:35Z","timestamp":1789127435000},"source":"Crossref","is-referenced-by-count":0,"title":["Sparsentan\u2013SGLT2 inhibitor combination therapy in trials of IgA nephropathy"],"prefix":"10.1093","author":[{"given":"Isabelle","family":"Ayoub","sequence":"first","affiliation":[{"name":"Division of Nephrology, Ohio State University , Columbus, OH ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Alperovich","sequence":"additional","affiliation":[{"name":"CSL Vifor , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radko","family":"Komers","sequence":"additional","affiliation":[{"name":"Travere Therapeutics, Inc. , San Diego, CA 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H","family":"Rovin","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Ohio State University , Columbus, OH ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hira","family":"Siktel","sequence":"additional","affiliation":[{"name":"Idaho Kidney Institute , Idaho Falls, ID ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6862-1941","authenticated-orcid":false,"given":"Sydney C W","family":"Tang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital ,","place":["Hong Kong"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"2026100505074633300_bib1","doi-asserted-by":"publisher","first-page":"727","DOI":"10.2215\/CJN.0000000000000135","article-title":"Long-term 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