Safety and efficacy of sofosbuvir‐containing regimens in hepatitis C‐infected patients with impaired renal function

• DOI: 10.1111/liv.13102
• Publication Date: 2016-02-29T13:25:53Z
• Authors: Varun Saxena; Farrukh M. Koraishy; Meghan E. Sise; Joseph K. Lim; Monica Schmidt; Raymond T. Chung; Annmarie Liapakis; David R. Nelson; Michael W. Fried; Norah A. Terrault
• Keywords: Liver Cirrhosis; Male; Kidney Disease; Sustained Virologic Response; Databases, Factual; Clinical sciences; Hepacivirus; Hepatitis; 0302 clinical medicine; Simeprevir; 80 and over; Renal Insufficiency; Longitudinal Studies; Chronic; Aged, 80 and over; liver transplantation; Liver Disease; sustained virologic response; Middle Aged; Hepatitis C; 3. Good health; haemodialysis; Europe; Infectious Diseases; 6.1 Pharmaceuticals; Combination; Regression Analysis; Drug Therapy, Combination; Female; decompensated cirrhosis; Glomerular Filtration Rate; Adult; Adolescent; Clinical Sciences; Clinical Trials and Supportive Activities; Renal and urogenital; 610; Antiviral Agents; Databases; Young Adult; 03 medical and health sciences; Drug Therapy; Clinical Research; Renal Dialysis; HCV-TARGET; Humans; Factual; Aged; Biomedical and Clinical Sciences; Gastroenterology & Hepatology; Hepatitis C, Chronic; Good Health and Well Being; Multivariate Analysis; North America; Sofosbuvir; Digestive Diseases

AbstractBackground & AimsRenal clearance is the major elimination pathway for sofosbuvir (SOF). We assessed the safety and efficacy of SOF‐containing regimens in patients with varying baseline estimated glomerular filtration rate (eGFR).MethodsHCV‐TARGET database is a multicentre, longitudinal ‘real‐world’ treatment cohort.ResultsA total of 1789 patients [genotypes 1 (72%), 2 (17%) 3 (9%), 4–6 (2%)] had baseline eGFR determination: 73 with eGFR≤45 (18 with eGFR≤30, 5 on dialysis) were compared to 1716 with eGFR>45 ml/min/1.73 m2. Patients with baseline eGFR≤45 vs. >45 differed in being female (55% vs. 36%), age ≥65 years (24% vs. 16%), Black race (22% vs. 12%), having cirrhosis with decompensation (73% vs. 24%) and being post‐transplant (49% vs. 10%), all P < 0.05. All patients with eGFR≤45 were treated with SOF 400 mg/day (including those on haemodialysis) and had median starting ribavirin (RBV) dose of 800 mg (IQR: 400–1200). Sustained virologic response (SVR) frequencies were similar across eGFR groups, ranging from 82–83%. Patients with eGFR ≤45 more frequently experienced anaemia, worsening renal function and serious AEs (all P < 0.05), and these associations persisted when limiting analysis to RBV‐free regimens. Patients with baseline eGFR≤30 and eGFR 31–45 had similar frequencies of efficacy and safety outcomes.ConclusionsSustained viral clearance was achieved in 83% of patients with renal impairment (eGFR ≤45 ml/min/1.73 m2) treated with SOF‐containing regimens. However, these patients had higher rates of anaemia, worsening renal dysfunction and serious adverse events regardless of use of RBV. Patient with renal impairment require close monitoring and should be treated by providers extensively experienced with SOF‐containing regimens.