Glecaprevir/Pibrentasvir Treatment in Liver or Kidney Transplant Patients With Hepatitis C Virus Infection
Journal
Hepatology
Journal Volume
68
Journal Issue
4
Pages
1298-1307
Date Issued
2018
Author(s)
Reau N.
Kwo P.Y.
Rhee S.
Brown R.S.
Jr.
Agarwal K.
Angus P.
Gane E.
Mantry P.S.
Mutimer D.
Reddy K.R.
Tran T.T.
Hu Y.B.
Gulati A.
Krishnan P.
Dumas E.O.
Porcalla A.
Shulman N.S.
Liu W.
Samanta S.
Trinh R.
Forns X.
Abstract
Well-tolerated, ribavirin-free, pangenotypic hepatitis C virus (HCV) treatments for transplant recipients remain a high priority. Once-daily glecaprevir/pibrentasvir demonstrates high rates of sustained virologic response at 12 weeks posttreatment (SVR12) across all major HCV genotypes (GTs). This trial evaluated the safety and efficacy of glecaprevir/pibrentasvir for patients with chronic HCV GT1-6 infection who had received a liver or kidney transplant. MAGELLAN-2 was a phase 3, open-label trial conducted in patients who were ?3 months posttransplant. Patients without cirrhosis who were HCV treatment-naive (GT1-6) or treatment-experienced (GT1, 2, 4-6; with interferon-based therapy with or without sofosbuvir, or sofosbuvir plus ribavirin) received glecaprevir/pibrentasvir (300/120 mg) once daily for 12 weeks. The primary endpoint compared the percentage of patients receiving glecaprevir/pibrentasvir with SVR12 to a historic SVR12 rate based on the standard of care. Safety of glecaprevir/pibrentasvir was assessed. In total, 80 liver transplant and 20 kidney transplant patients participated in the trial. Most patients had no or minimal fibrosis (80% had fibrosis scores F0-F1) and were infected with HCV GT1 (57%) or GT3 (24%). The overall SVR12 was 98% (n/N = 98/100; 95% confidence interval, 95.3%–100%), which exceeded the prespecified historic standard-of-care SVR12 threshold of 94%. One patient experienced virologic failure. One patient discontinued because of an adverse event considered to be unrelated to treatment; this patient achieved SVR12. Adverse events were mostly mild in severity, and laboratory abnormalities were infrequent. Conclusion: Once-daily glecaprevir/pibrentasvir for 12 weeks is a well-tolerated and efficacious, ribavirin-free treatment for patients with chronic HCV GT1-6 infection who have received a liver or kidney transplant. (ClinicalTrials.gov NCT02692703.) (Hepatology 2018; 00:000-000). ? 2018 The Authors. Hepatology published by Wiley Periodicals, Inc. on behalf of American Association for the Study of Liver Diseases.
SDGs
Other Subjects
alanine aminotransferase; amino acid; bilirubin; clarithromycin; creatinine; cyclosporine; everolimus; glecaprevir plus pibrentasvir; peginterferon; rapamycin; ribavirin; sofosbuvir; tacrolimus; virus RNA; ABT-493; benzimidazole derivative; pibrentasvir; quinoxaline derivative; sulfonamide; adult; aged; alanine aminotransferase blood level; anticoagulant therapy; antiviral therapy; Article; bilirubin blood level; cerebrovascular accident; chronic hepatitis C; combination drug therapy; creatinine blood level; creatinine clearance; diarrhea; disease severity; drug efficacy; drug safety; estimated glomerular filtration rate; fatigue; female; headache; health care quality; Hepatitis C virus genotype 1; Hepatitis C virus genotype 2; Hepatitis C virus genotype 3; Hepatitis C virus genotype 4; Hepatitis C virus genotype 5; Hepatitis C virus genotype 6; human; immunosuppressive treatment; immunotherapy; international normalized ratio; kidney graft; kidney graft rejection; liver graft; liver graft rejection; major clinical study; male; medication compliance; multicenter study; nausea; open study; patient compliance; phase 3 clinical trial; priority journal; pruritus; relapse; side effect; sustained virologic response; urinary tract infection; chronic hepatitis C; clinical trial; dose response; drug administration; graft recipient; graft rejection; graft survival; international cooperation; kidney transplantation; liver transplantation; middle aged; prognosis; risk assessment; treatment outcome; Adult; Aged; Benzimidazoles; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Graft Rejection; Graft Survival; Hepatitis C, Chronic; Humans; Internationality; Kidney Transplantation; Liver Transplantation; Male; Middle Aged; Prognosis; Quinoxalines; Risk Assessment; Sulfonamides; Transplant Recipients; Treatment Outcome
Publisher
John Wiley and Sons Inc.
Type
journal article