Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis

Nenhuma Miniatura disponível
Citações na Scopus
10
Tipo de produção
article
Data de publicação
2023
DOI
Scopus
Web of Science
PubMed
Dimensions
Título da Revista
ISSN da Revista
Título do Volume
Editora
MASSACHUSETTS MEDICAL SOC
Autores
RHEAULT, Michelle N.
ALPERS, Charles E.
BARRATT, Jonathan
BIELER, Stewart
CANETTA, Pietro
CHAE, Dong-Wan
COPPOCK, Gaia
DIVA, Ulysses
GESUALDO, Loreto
HEERSPINK, Hiddo J. L.
Citação
NEW ENGLAND JOURNAL OF MEDICINE, v.389, n.26, p.2436-2445, 2023
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
BackgroundAn unmet need exists for focal segmental glomerulosclerosis (FSGS) treatment. In an 8-week, phase 2 trial, sparsentan, a dual endothelin-angiotensin receptor antagonist, reduced proteinuria in patients with FSGS. The efficacy and safety of longer-term treatment with sparsentan for FSGS are unknown.MethodsIn this phase 3 trial, we enrolled patients with FSGS (without known secondary causes) who were 8 to 75 years of age; patients were randomly assigned to receive sparsentan or irbesartan (active control) for 108 weeks. The surrogate efficacy end point assessed at the prespecified interim analysis at 36 weeks was the FSGS partial remission of proteinuria end point (defined as a urinary protein-to-creatinine ratio of <= 1.5 [with protein and creatinine both measured in grams] and a >40% reduction in the ratio from baseline). The primary efficacy end point was the estimated glomerular filtration rate (eGFR) slope at the time of the final analysis. The change in eGFR from baseline to 4 weeks after the end of treatment (week 112) was a secondary end point. Safety was also evaluated.ResultsA total of 371 patients underwent randomization: 184 were assigned to receive sparsentan and 187 to receive irbesartan. At 36 weeks, the percentage of patients with partial remission of proteinuria was 42.0% in the sparsentan group and 26.0% in the irbesartan group (P=0.009), a response that was sustained through 108 weeks. At the time of the final analysis at week 108, there were no significant between-group differences in the eGFR slope; the between-group difference in total slope (day 1 to week 108) was 0.3 ml per minute per 1.73 m(2) of body-surface area per year (95% confidence interval [CI], -1.7 to 2.4), and the between-group difference in the slope from week 6 to week 108 (i.e., chronic slope) was 0.9 ml per minute per 1.73 m(2) per year (95% CI, -1.3 to 3.0). The mean change in eGFR from baseline to week 112 was -10.4 ml per minute per 1.73 m(2) with sparsentan and -12.1 ml per minute per 1.73 m(2) with irbesartan (difference, 1.8 ml per minute per 1.73 m2; 95% CI, -1.4 to 4.9). Sparsentan and irbesartan had similar safety profiles, and the frequency of adverse events was similar in the two groups.ConclusionsAmong patients with FSGS, there were no significant between-group differences in eGFR slope at 108 weeks, despite a greater reduction in proteinuria with sparsentan than with irbesartan. (Funded by Travere Therapeutics; DUPLEX ClinicalTrials.gov number, NCT03493685.)
Palavras-chave
URI
https://observatorio.fm.usp.br/handle/OPI/58789
Referências
  1. Benigni A, 2021, PEDIATR NEPHROL, V36, P763, DOI 10.1007/s00467-020-04518-2
  2. Campbell KN, 2022, KIDNEY MED, V4, DOI 10.1016/j.xkme.2022.100457
  3. Carter SA, 2020, CLIN J AM SOC NEPHRO, V15, P673, DOI 10.2215/CJN.13101019
  4. Du YH, 2022, ANN PALLIAT MED, V11, P1093, DOI 10.21037/apm-22-212
  5. Gipson DS, 2022, JAMA NETW OPEN, V5, DOI 10.1001/jamanetworkopen.2022.28701
  6. Grams ME, 2019, J AM SOC NEPHROL, V30, P1746, DOI 10.1681/ASN.2019010008
  7. Heerspink HJL, 2023, LANCET, V401, P1584, DOI 10.1016/S0140-6736(23)00569-X
  8. Heerspink HJL, 2019, LANCET, V393, P1937, DOI 10.1016/S0140-6736(19)30772-X
  9. Inker LA, 2023, NAT MED, V29, P1867, DOI 10.1038/s41591-023-02418-0
  10. Komers R, 2020, KIDNEY INT REP, V5, P494, DOI 10.1016/j.ekir.2019.12.017
  11. Komers R, 2016, AM J PHYSIOL-REG I, V310, pR877, DOI 10.1152/ajpregu.00425.2015
  12. Kowala MC, 2004, J PHARMACOL EXP THER, V309, P275, DOI 10.1124/jpet.103.055855
  13. Levey AS, 2020, AM J KIDNEY DIS, V75, P84, DOI 10.1053/j.ajkd.2019.06.009
  14. Levey AS, 2009, ANN INTERN MED, V150, P604, DOI 10.7326/0003-4819-150-9-200905050-00006
  15. Lieberman K., 2023, KIDNEY INT REP, V8, pS128
  16. Mann JFE, 2010, J AM SOC NEPHROL, V21, P527, DOI 10.1681/ASN.2009060593
  17. Murugesan N, 2005, J MED CHEM, V48, P171, DOI 10.1021/jm049548x
  18. Rosenberg AZ, 2017, CLIN J AM SOC NEPHRO, V12, P502, DOI 10.2215/CJN.05960616
  19. Schwartz GJ, 2009, CLIN J AM SOC NEPHRO, V4, P1832, DOI 10.2215/CJN.01640309
  20. Schwartz GJ, 2009, J AM SOC NEPHROL, V20, P629, DOI 10.1681/ASN.2008030287
  21. Shabaka A, 2020, NEPHRON, V144, P413, DOI 10.1159/000508099
  22. Staplin N, 2022, LANCET, V400, P1788, DOI 10.1016/S0140-6736(22)02074-8
  23. Thompson A, 2019, CLIN J AM SOC NEPHRO, V14, P469, DOI 10.2215/CJN.08600718
  24. Trachtman H, 2023, KIDNEY INT REP, V8, P2017, DOI 10.1016/j.ekir.2023.07.022
  25. Trachtman H, 2018, J AM SOC NEPHROL, V29, P2745, DOI 10.1681/ASN.2018010091
  26. Troost JP, 2021, AM J KIDNEY DIS, V77, P216, DOI 10.1053/j.ajkd.2020.04.014
  27. Troost JP, 2018, CLIN J AM SOC NEPHRO, V13, P414, DOI 10.2215/CJN.04780517
  28. Troyanov S, 2005, J AM SOC NEPHROL, V16, P1061, DOI 10.1681/ASN.2004070593
  29. Wheeler DC, 2022, NEPHROL DIAL TRANSPL, V37, P1647, DOI 10.1093/ndt/gfab335

Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM