Treatment With Ledipasvir-Sofosbuvir for 12 or 24 Weeks in Kidney Transplant Recipients With Chronic Hepatitis C Virus Genotype 1 or 4 Infection: A Randomized Trial.

Abstract

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 interferon- and 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.

PRIMARY FUNDING SOURCE:

Gilead Sciences.

• Authors: Massimo Colombo, Alessio Aghemo, Hong Liu, Jie Zhang, Hadas Dvory-Sobol, Robert Hyland, Chohee Yun, Benedetta Massetto, Diana M Brainard, John G McHutchison, Marc Bourlière, Markus Peck-Radosavljevic, Michael Manns, Stanislas Pol
• Journal: Annals of internal medicine (Ann Intern Med) Vol. 166 Issue 2 Pg. 109-117 (Jan 17 2017) ISSN: 1539-3704 [Electronic] United States
• PMID: 27842383 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Antiviral Agents
• Benzimidazoles
• Fluorenes
• Immunosuppressive Agents
• ledipasvir
• Sofosbuvir

Topics

• Adult
• Aged
• Antiviral Agents (adverse effects, therapeutic use)
• Benzimidazoles (adverse effects, therapeutic use)
• Drug Administration Schedule
• Drug Resistance, Viral
• Drug Therapy, Combination
• Female
• Fluorenes (adverse effects, therapeutic use)
• Genotype
• Glomerular Filtration Rate (drug effects)
• Hepatitis C, Chronic (blood, drug therapy, genetics)
• Humans
• Immunosuppressive Agents (administration & dosage)
• Kidney Transplantation
• Male
• Middle Aged
• Sofosbuvir (adverse effects, therapeutic use)