TY - JOUR
T1 - Treatment with ledipasvir-sofosbuvir for 12 or 24 weeks in kidney transplant recipients with chronic hepatitis C virus genotype 1 or 4 infection
T2 - A randomized trial
AU - Colombo, Massimo
AU - Aghemo, Alessio
AU - Liu, Hong
AU - Zhang, Jie
AU - Dvory-Sobol, Hadas
AU - Hyland, Robert
AU - Yun, Chohee
AU - Massetto, Benedetta
AU - Brainard, Diana M.
AU - McHutchison, John G.
AU - Bourlière, Marc
AU - Peck-Radosavljevic, Markus
AU - Manns, Michael
AU - Pol, Stanislas
PY - 2017/1/17
Y1 - 2017/1/17
N2 - Background: Use of interferon and ribavirin to treat chronic hepatitis C virus (HCV) infection in kidney transplant recipients is limited because of the risk for allograft rejection and poor tolerability. Objective: To evaluate the safety and efficacy of the interferonand ribavirin-free regimen ledipasvir-sofosbuvir in kidney transplant recipients with chronic genotype 1 or 4 HCV infection. Design: Randomized, phase 2, open-label study. (ClinicalTrials.gov: NCT02251717) Setting: 5 sites in Europe. Patients: Treatment-naive or -experienced kidney transplant recipients with chronic genotype 1 or 4 HCV infection, with or without compensated cirrhosis, and with an estimated glomerular filtration rate (EGFR) of 40 mL/min or greater were randomly assigned 1:1 to receive ledipasvir (90 mg) and sofosbuvir (400 mg) for 12 or 24 weeks. Measurements: The primary end point was sustained virologic response at 12 weeks after therapy ended (SVR12). Results: Among 114 patients, the median age was 53 years, 58% were male, 91% had genotype 1 infection, 69% were treatment naive, and 15% had compensated cirrhosis. The median EGFR was 56 mL/min (range, 35 to 135 mL/min). One hundred percent of patients (57 of 57) treated for 12 weeks (95% CI, 94% to 100%) and 100% of those (57 of 57) treated for 24 weeks (CI, 94% to 100%) achieved SVR12. Serious adverse events were reported in 13 patients (11%). Of these, 3 events - syncope, pulmonary embolism, and serum creatinine increase - in 3 patients were determined to be treatment related. One patient permanently discontinued treatment because of an adverse event (syncope). The most frequent adverse events overall were headache (n = 22 [19%]), asthenia (n = 16 [14%]), and fatigue (n= 11 [10%]). Limitations: The study was open label, no inferential statistics were planned, and only patients with genotype 1 or 4 infection were included. Few patients with HCV genotype 1a and cirrhosis were enrolled. Conclusion: Treatment with ledipasvir-sofosbuvir for 12 or 24 weeks was well-tolerated and seemed to have an acceptable safety profile among kidney transplant recipients with HCV genotype 1 or 4 infection, all of whom achieved SVR12.
AB - Background: Use of interferon and ribavirin to treat chronic hepatitis C virus (HCV) infection in kidney transplant recipients is limited because of the risk for allograft rejection and poor tolerability. Objective: To evaluate the safety and efficacy of the interferonand ribavirin-free regimen ledipasvir-sofosbuvir in kidney transplant recipients with chronic genotype 1 or 4 HCV infection. Design: Randomized, phase 2, open-label study. (ClinicalTrials.gov: NCT02251717) Setting: 5 sites in Europe. Patients: Treatment-naive or -experienced kidney transplant recipients with chronic genotype 1 or 4 HCV infection, with or without compensated cirrhosis, and with an estimated glomerular filtration rate (EGFR) of 40 mL/min or greater were randomly assigned 1:1 to receive ledipasvir (90 mg) and sofosbuvir (400 mg) for 12 or 24 weeks. Measurements: The primary end point was sustained virologic response at 12 weeks after therapy ended (SVR12). Results: Among 114 patients, the median age was 53 years, 58% were male, 91% had genotype 1 infection, 69% were treatment naive, and 15% had compensated cirrhosis. The median EGFR was 56 mL/min (range, 35 to 135 mL/min). One hundred percent of patients (57 of 57) treated for 12 weeks (95% CI, 94% to 100%) and 100% of those (57 of 57) treated for 24 weeks (CI, 94% to 100%) achieved SVR12. Serious adverse events were reported in 13 patients (11%). Of these, 3 events - syncope, pulmonary embolism, and serum creatinine increase - in 3 patients were determined to be treatment related. One patient permanently discontinued treatment because of an adverse event (syncope). The most frequent adverse events overall were headache (n = 22 [19%]), asthenia (n = 16 [14%]), and fatigue (n= 11 [10%]). Limitations: The study was open label, no inferential statistics were planned, and only patients with genotype 1 or 4 infection were included. Few patients with HCV genotype 1a and cirrhosis were enrolled. Conclusion: Treatment with ledipasvir-sofosbuvir for 12 or 24 weeks was well-tolerated and seemed to have an acceptable safety profile among kidney transplant recipients with HCV genotype 1 or 4 infection, all of whom achieved SVR12.
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U2 - 10.7326/M16-1205
DO - 10.7326/M16-1205
M3 - Article
C2 - 27842383
AN - SCOPUS:85016986156
VL - 166
SP - 109
EP - 117
JO - Annals of Internal Medicine
JF - Annals of Internal Medicine
SN - 0003-4819
IS - 2
ER -