Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension

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art_HOEPER_Phase_3_Trial_of_Sotatercept_for_Treatment_of_2023.PDF (673.18 KB)
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102
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article
Data de publicação
2023
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Scopus
Web of Science
PubMed
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MASSACHUSETTS MEDICAL SOC
Autores
HOEPER, Marius M.
BADESCH, David B.
GHOFRANI, H. Ardeschir
GIBBS, J. Simon R.
GOMBERG-MAITLAND, Mardi
MCLAUGHLIN, Vallerie V.
PRESTON, Ioana R.
WAXMAN, Aaron B.
GRUENIG, Ekkehard
Citação
NEW ENGLAND JOURNAL OF MEDICINE, v.388, n.16, p.1478-1490, 2023
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BACKGROUNDPulmonary arterial hypertension is a progressive disease involving proliferative remodeling of the pulmonary vessels. Despite therapeutic advances, the disease-associated morbidity and mortality remain high. Sotatercept is a fusion protein that traps activins and growth differentiation factors involved in pulmonary arterial hypertension.METHODSWe conducted a multicenter, double-blind, phase 3 trial in which adults with pulmonary arterial hypertension (World Health Organization [WHO] functional class II or III) who were receiving stable background therapy were randomly assigned in a 1:1 ratio to receive subcutaneous sotatercept (starting dose, 0.3 mg per kilogram of body weight; target dose, 0.7 mg per kilogram) or placebo every 3 weeks. The primary end point was the change from baseline at week 24 in the 6-minute walk distance. Nine secondary end points, tested hierarchically in the following order, were multicomponent improvement, change in pulmonary vascular resistance, change in N-terminal pro-B-type natriuretic peptide level, improvement in WHO functional class, time to death or clinical worsening, French risk score, and changes in the Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Physical Impacts, Cardiopulmonary Symptoms, and Cognitive-Emotional Impacts domain scores; all were assessed at week 24 except time to death or clinical worsening, which was assessed when the last patient completed the week 24 visit.RESULTSA total of 163 patients were assigned to receive sotatercept and 160 to receive placebo. The median change from baseline at week 24 in the 6-minute walk distance was 34.4 m (95% confidence interval [CI], 33.0 to 35.5) in the sotatercept group and 1.0 m (95% CI, -0.3 to 3.5) in the placebo group. The Hodges-Lehmann estimate of the difference between the sotatercept and placebo groups in the change from baseline at week 24 in the 6-minute walk distance was 40.8 m (95% CI, 27.5 to 54.1; P < 0.001). The first eight secondary end points were significantly improved with sotatercept as compared with placebo, whereas the PAH-SYMPACT Cognitive-Emotional Impacts domain score was not. Adverse events that occurred more frequently with sotatercept than with placebo included epistaxis, dizziness, telangiectasia, increased hemoglobin levels, thrombocytopenia, and increased blood pressure.CONCLUSIONSIn patients with pulmonary arterial hypertension who were receiving stable background therapy, sotatercept resulted in a greater improvement in exercise capacity (as assessed by the 6-minute walk test) than placebo. (Funded by Acceleron Pharma, a subsidiary of MSD; STELLAR ClinicalTrials.gov number, .)
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https://observatorio.fm.usp.br/handle/OPI/56025
Referências
  1. Andre P, 2022, FRONT MED-LAUSANNE, V8, DOI 10.3389/fmed.2021.814222
  2. [Anonymous], 1996, BRIT MED J, V313, P1448
  3. Boucly A, 2017, EUR RESPIR J, V50, DOI 10.1183/13993003.00889-2017
  4. Chin KM, 2018, CHEST, V154, P848, DOI 10.1016/j.chest.2018.04.027
  5. Guignabert C, 2021, EUR RESPIR J, V57, DOI 10.1183/13993003.02341-2020
  6. Hassoun PM, 2021, NEW ENGL J MED, V385, P2361, DOI 10.1056/NEJMra2000348
  7. Hoeper MM, 2022, J HEART LUNG TRANSPL, V41, P971, DOI 10.1016/j.healun.2022.03.011
  8. Hoeper MM, 2022, EUR RESPIR J, V59, DOI 10.1183/13993003.02024-2021
  9. Humbert Marc, 2023, Eur Respir J, V61, DOI 10.1183/13993003.01347-2022
  10. Humbert M, 2023, EUR RESPIR J, V61, DOI [10.1093/eurheartj/ehac237, 10.1183/13993003.00879-2022]
  11. Humbert M, 2021, NEW ENGL J MED, V384, P1204, DOI 10.1056/NEJMoa2024277
  12. Humbert M, 2019, EUR RESPIR J, V53, DOI 10.1183/13993003.01887-2018
  13. International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, 2002, GUID GOOD CLIN PRACT
  14. Joshi SR, 2022, SCI REP-UK, V12, DOI 10.1038/s41598-022-11435-x
  15. McCollister D, 2016, RESP RES, V17, DOI 10.1186/s12931-016-0388-6
  16. Mehrotra DV, 2010, AM STAT, V64, P121, DOI 10.1198/tast.2010.08121
  17. MIETTINEN O, 1985, STAT MED, V4, P213, DOI 10.1002/sim.4780040211
  18. Ryanto GRT, 2021, NAT COMMUN, V12, DOI 10.1038/s41467-021-21961-3
  19. Sitbon O, 2015, NEW ENGL J MED, V373, P2522, DOI 10.1056/NEJMoa1503184
  20. van Delden JJM, 2017, JAMA-J AM MED ASSOC, V317, P135, DOI 10.1001/jama.2016.18977
  21. Yung LM, 2020, SCI TRANSL MED, V12, DOI 10.1126/scitranslmed.aaz5660

Coleções
Artigos e Materiais de Revistas Científicas - FM/MCP
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/09
Artigos e Materiais de Revistas Científicas - ODS/03