BOSTON — Twelve or 24 weeks of treatment with ledipasvir and sofosbuvir plus ribavirin yielded sustained virologic response rates higher than 90% in patients with hepatitis C virus recurrence after liver transplantation, according to data presented at The Liver Meeting.
The prospective, multicenter study included 223 patients with HCV genotype 1 and 4 infection who had a liver transplant. All received treatment with ledipasvir 90 mg per day and sofosbuvir 400 mg per day plus ribavirin for 12 (n=112) or 24 weeks (n=111). The primary endpoint was SVR 12 weeks after completion of study treatment.
Recently, “ledipasvir and sofosbuvir have been coformulated into a single tablet taken once daily,” K. Rajender Reddy, MD, from the University of Pennsylvania School of Medicine, said during a presentation. The combination treatment is marketed as Harvoni (Gilead).
The analysis included both treatment-naive and treatment-experienced patients. Other inclusion criteria included fibrosis stage F0 to F3 (n=111); Child-Pugh-Turcotte (CPT) class A (n=51), B (n=52) and C (n=9) with cirrhosis; and estimated glomerular filtration rate greater than 40 mL/min.
“The study had broad inclusion criteria,” Reddy said. “Patients had to have been at least 3 months out from liver transplant. Patients with hepatocellular carcinoma were excluded.”
During a presentation, Reddy reported ribavirin dose escalation for patients with CPT class B and C and weight-based regimen for those with F0 to F3 fibrosis and CPT class A cirrhosis.
Median time from transplant to treatment was 2.9 to 8.1 years.
SVR12 among patients with F0 to F3 fibrosis was 96% for those who received 12 weeks of treatment and 98% for 24 weeks of treatment.
Among patients with CPT class A, SVR12 was 96% for 12 and 24 weeks of treatment. Among patients with CPT class B, SVR12 was 85% for those who received 12 weeks of treatment and 83% for 24 weeks of treatment. Among those with CPT class C, SVR12 was 60% for those who received 12 weeks of treatment and 67% for 24 weeks of treatment, Reddy said during a session.
“There were six relapses among the 223 patients in the study,” Reddy said.
Seven patients died and two withdrew consent. There were no on-treatment virologic failures or breakthroughs, according to Reddy.
More patients with CPT class B demonstrated improvement in MELD score compared with patients with CPT class A. Eighteen patients had unchanged MELD scores, Reddy said.
In other findings, the researchers observed a significant decrease in bilirubin, regardless of treatment duration, and a significant improvement in albumin in all groups.
Anemia and portal vein thrombosis were the most commonly reported adverse events. While most patients experienced an adverse event, grade 3 or 4 events were uncommon. “These events did not appear to be related to longer duration of therapy,” he said.
“In patients with recurrent HCV post-transplantation, treatment with ledipasvir and sofosbuvir with ribavirin was associated with high rates of SVR regardless of disease severity or duration of therapy,” Reddy concluded. – by Rob Volansky
For more information:
Reddy KR. Abstract 8. Presented at: The Liver Meeting; Nov. 7-11, 2014; Boston.
Disclosure: Reddy reports serving on advisory committees/review panels for AbbVie, Bristol-Myers Squibb, Genentech/Roche, Gilead, Janssen, Merck, Novartis and Vertex, and grant/research support from AbbVie, Bristol-Myers Squibb, Gilead, Ikaria, Janssen and Merck. See the abstract for the other researchers’ relevant financial disclosures.