Direct-acting antiviral (DAA) treatment with sofosbuvir plus ledipasvir (SOF/LDV) was safe and effective for treating transfusion-related hepatitis C virus (HCV) infection in patients with thalassemia. The treatment regimen did not require the use of interferons or ribavirin. These study results were published in Alimentary Pharmacology & Therapeutics.
The majority of patients with thalassemia who were treated with regular blood transfusions before 1990 have chronic HCV infection resulting from contaminated transfusions. Antiviral therapy may reduce the risk for HCV-related cirrhosis and hepatocellular cancer. Standard treatment for HCV in the thalassemia population consists of pegylated interferon and ribavirin (Peg-IFN/RBV), whose use is significantly limited by adverse effects. In particular, ribavirin use may lead to more blood transfusions and thereby increase the risk for iron overload.
Regimens that are free of interferons typically use DAAs, but patients with thalassemia were excluded from studies evaluating DAAs for HCV. SOF/LDV is a combination DAA regimen that produces a sustained virologic response (SVR) of ≥94% in both treatment-naive and previously treated patients with HCV genotype 1 or 4. In addition, SOF/LDV is unlikely to cause drug-drug interactions with medications commonly used to treat thalassemia.
Researchers compared the safety and efficacy of SOF/LDV vs Peg-IFN/RBV for 12 weeks in patients with thalassemia major and HCV genotype 1 or 4.
A total of 100 patients received fixed-dose combination SOF 400 mg/LDV 90 mg as a single pill taken once daily for 12 weeks. The control arm was historical and consisted of 96 patients who had received Pegasys 180 µg once weekly plus ribavirin 1000 or 1200 mg based on body weight. In both treatment groups, approximately 60% and 16% of patients were treatment-naive and had liver cirrhosis, respectively.
The majority of patients in the SOF/LDV (90%) and Peg-IFN/RBV (74%) groups had HCV genotype 1 infection. A total of 7% in both groups had HCV genotype 4 infection. The control group had higher mean baseline HCV RNA levels than the SOF/LDV group (142,000,000 IU/mL vs 952,000 IU/mL) but this difference was not statistically significant.
In the SOF/LDV group, SVR at 12 weeks posttreatment (SVR12) was 98%. Of the 2 virological failures, 1 relapsed at 4 weeks and 1 relapsed at 8 weeks posttreatment. Both patients were treatment-naive, noncirrhotic, and had HCV genotype 1. All SOF/LDV patients had undetectable HCV RNA by treatment week 8.
In the Peg-IFN/RBV group, SVR at 24 weeks posttreatment (SVR24) was 47.9%. Nearly all control patients achieving SVR24 were noncirrhotic. A total of 72 (75%) Peg-IFN/RBV patients had undetectable HCV RNA at treatment week 12, but 25 relapsed by week 24 posttreatment. Most nonresponders in the control group were patients who discontinued treatment because of ribavirin or interferon intolerance.
The rate of adverse events was 76% in the SOF/LDV group, most commonly fatigue and nausea. No patients receiving SOF/LDV discontinued treatment because of adverse events, compared with 23% of those in the Peg-IFN/RBV group. There were no serious adverse events in either group.
By treatment week 12, the number of transfusions significantly increased among patients receiving Peg-IFN/RBV, but not among those receiving SOF/LDV. In addition, hemoglobin levels at 12 weeks posttreatment were lower in the control group than in the SOF/LDV group (8.83 vs 10.56 g/dL).
“In conclusion, SOF/LDV [fixed dose combination] for 12 weeks provides simple, highly effective treatment for patients with thalassaemia major and concomitant HCV [genotype 1 or genotype 4] infections. It appears an effective and safe regimen in naïve patients with cirrhosis regardless of the chelators adopted,” the investigators wrote.
“This regimen may represent a decisive treatment to reduce morbidity and mortality in developing countries, where both the risk of HCV infection related to blood transfusion and the prevalence of thalassaemia continue to represent a concern for larger numbers of subjects,” they added.
The investigators report financial relationships with Janssen-Cilag, MSD, ROCHE, Gilead Sciences, and BMS. The study medications were supplied by Gilead Sciences.
- Mangia A, Sarli R, Gamberini R, et al. Randomised clinical trial: sofosbuvir and ledipasvir in patients with transfusion-dependent thalassaemia and HCV genotype 1 or 4 infection. Aliment Pharmacol Ther. 2017;46(4):424-431.