1. Sofosbuvir and risk of estimated glomerular filtration rate decline or end‐stage renal disease in patients with renal impairment
- Author
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Mark Sulkowski, Laura E. Telep, Massimo Colombo, Francois Durand, K. Rajender Reddy, Eric Lawitz, Marc Bourlière, Nelson Cheinquer, Stacey Scherbakovsky, Liyun Ni, Lindsey Force, Heribert Ramroth, Anuj Gaggar, Anand P. Chokkalingam, Meghan E. Sise, Johns Hopkins University School of Medicine [Baltimore], Gilead Sciences, Inc. [Foster City, CA, USA], IRCCS Ospedale San Raffaele [Milan, Italy], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), University of Texas Health Science Center at San Antonio [San Antonio, Tx, USA], Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Massachusetts General Hospital [Boston, MA, USA], and Harvard Medical School [Boston] (HMS)
- Subjects
Male ,MESH: Antiviral Agents ,[SDV]Life Sciences [q-bio] ,MESH: Renal Insufficiency, Chronic ,GS-331007 ,Antiviral Agents ,sofosbuvir ,MESH: Renal Insufficiency ,Humans ,Pharmacology (medical) ,Renal Insufficiency ,Renal Insufficiency, Chronic ,Retrospective Studies ,direct-acting antiviral ,end-stage renal disease ,MESH: Humans ,Hepatology ,Gastroenterology ,MESH: Sofosbuvir ,MESH: Retrospective Studies ,MESH: Male ,MESH: Glomerular Filtration Rate ,MESH: Kidney Failure, Chronic ,Disease Progression ,Kidney Failure, Chronic ,dialysis ,Female ,MESH: Disease Progression ,MESH: Female ,chronic kidney disease ,Glomerular Filtration Rate - Abstract
Background: Sofosbuvir, a prodrug nucleoside inhibitor of hepatitis C virus, has a predominant circulating metabolite that is renally eliminated. Whether sofosbuvir is associated with chronic kidney disease (CKD) progression is not well understood.Methods: We performed a retrospective analysis of patients with estimated glomerular filtration rate (eGFR) 30-89 mL/min/1.73 m2 treated with sofosbuvir in 76 Phase 2/3 registrational trials. We evaluated eGFR at each study visit. Separately, we performed a retrospective analysis of an administrative claims database (IQVIA PharMetrics Plus™) to compare the risk of incident end-stage renal disease (ESRD) associated with the use of sofosbuvir or non-sofosbuvir regimens among patients with CKD using propensity score methods. Exposure, CKD status and outcomes were determined using diagnosis and medication claim codes. Cox proportional hazards methods were used to estimate ESRD risk.Results: Among 4642 trial participants with baseline stage 2 CKD (eGFR 60-89 ml/min/1.73 m2 ) and 682 trial participants with stage 3 CKD (eGFR 30-59 ml/min/1.73 m2 ) mean (SD) eGFR improved from baseline to 4 weeks post-treatment (+0.7 [9.3] and +2.6 [8.8] ml/min/1.73 m2 , respectively; p < 0.001 each). In the second analysis, among 2042 patients with CKD receiving sofosbuvir-based regimens compared to 431 receiving non-sofosbuvir-based regimens, after adjusting for baseline covariates and weighting based on treatment propensity scores, there was no significant difference in risk of ESRD (adjusted HR = 0.85, 95% CI: 0.51-1.42).Conclusions: Clinical trial participants with CKD did not experience worsening eGFR during sofosbuvir-based treatment, and sofosbuvir was not associated with an increased risk of ESRD in patients with CKD in a nationally-representative administrative claims database.
- Published
- 2022
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