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Abstract Details
Sofosbuvir and risk of estimated glomerular filtration rate decline or end-stage renal disease in patients with renal impairment
Aliment Pharmacol Ther. 2022 Mar 2. doi: 10.1111/apt.16830. Online ahead of print.
Mark Sulkowski1, Laura E Telep2, Massimo Colombo3, Francois Durand4, K Rajender Reddy5, Eric Lawitz6, Marc Bourlière78, Nelson Cheinquer2, Stacey Scherbakovsky2, Liyun Ni2, Lindsey Force2, Heribert Ramroth2, Anuj Gaggar2, Anand P Chokkalingam2, Meghan E Sise9
Author information
Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Gilead Sciences, Inc., Foster City, California, USA.
M Colombo Liver Center, San Raffaele Hospital, Milan, Italy.
Hôpital Beaujon, University Paris Diderot, Clichy, France.
Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Texas Liver Institute, University of Texas Health Science Center, San Antonio, Texas, USA.
Hépato-Gastro-Entérologie, Hôpital Saint Joseph, Marseille, France.
INSERM 1252, IRD, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, Aix-Marseille University, Marseille, France.
Massachusetts General Hospital, Boston, Massachusetts, USA.
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.