Jeffrey W Jansen1,2, Travis W Linneman3, Gillian M Powderly3, Ryan P Moenster3,4, Leela Nayak5. 1. Department of Research, VA Saint Louis Health Care System, St. Louis, Missouri. 2. Department of Pharmacy, SCL St. Vincent Healthcare, Billings, Montana. 3. Department of Pharmacy, VA Saint Louis Health Care System, St. Louis, Missouri. 4. Department of Pharmacy Practice, Saint Louis College of Pharmacy, St. Louis, Missouri. 5. Department of Gastroenterology, Southeastern Louisiana Veterans Healthcare System, New Orleans, Louisiana.
Abstract
BACKGROUND: Hepatitis C remains a major cause of liver disease globally and is responsible for approximately 500 000 deaths annually. Newer direct-acting antivirals achieve cure rates at or above 90% with excellent tolerability for most patients. The literature focusing on identification of predictors of efficacy and safety with specific hepatitis C therapies has been inconclusive and often conflicting. METHODS: A retrospective, single-center, case-control analysis of all veteran patients aged ≥18 through ≤89 years who completed a treatment course of 8, 12, or 24 weeks with ledipasvir and sofosbuvir (LDV/SOF) combination therapy for hepatitis C infection was conducted. Patients who were identified and met inclusion criteria were assigned to either the case group (SVR12 failure; hepatitis C viral load detectable at least 11 weeks after therapy completion) or the control group (SVR12 success; hepatitis C viral load undetectable at least 11 weeks after therapy completion). RESULTS: Twenty-nine SVR12 failures and 411 SVR12 successes were included in the analysis. The overall failure rate was consistent with the current literature, at 6.6% (29/440). Bivariate analysis identified only baseline creatinine clearance >80 mL min-1 (Cockcroft-Gault) as a possible predictor of SVR12 failure (P = .026). In the multivariate analysis, pretreatment creatinine clearance >80 mL min-1 remained independently associated with SVR12 failure (odds ratio, 2.95; 95% confidence interval, 1.17-7.46; P = .023). CONCLUSIONS: In hepatitis C patients treated with LDV/SOF, a pretreatment creatinine clearance of >80 mL min-1 was associated with SVR12 failure.
BACKGROUND: Hepatitis C remains a major cause of liver disease globally and is responsible for approximately 500 000 deaths annually. Newer direct-acting antivirals achieve cure rates at or above 90% with excellent tolerability for most patients. The literature focusing on identification of predictors of efficacy and safety with specific hepatitis C therapies has been inconclusive and often conflicting. METHODS: A retrospective, single-center, case-control analysis of all veteran patients aged ≥18 through ≤89 years who completed a treatment course of 8, 12, or 24 weeks with ledipasvir and sofosbuvir (LDV/SOF) combination therapy for hepatitis C infection was conducted. Patients who were identified and met inclusion criteria were assigned to either the case group (SVR12 failure; hepatitis C viral load detectable at least 11 weeks after therapy completion) or the control group (SVR12 success; hepatitis C viral load undetectable at least 11 weeks after therapy completion). RESULTS: Twenty-nine SVR12 failures and 411 SVR12 successes were included in the analysis. The overall failure rate was consistent with the current literature, at 6.6% (29/440). Bivariate analysis identified only baseline creatinine clearance >80 mL min-1 (Cockcroft-Gault) as a possible predictor of SVR12 failure (P = .026). In the multivariate analysis, pretreatment creatinine clearance >80 mL min-1 remained independently associated with SVR12 failure (odds ratio, 2.95; 95% confidence interval, 1.17-7.46; P = .023). CONCLUSIONS: In hepatitis C patients treated with LDV/SOF, a pretreatment creatinine clearance of >80 mL min-1 was associated with SVR12 failure.
Entities:
Keywords:
clinical pharmacology; direct acting antivirals; hepatitis C virus; ledipasvir; sofosbuvir; treatment failure
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