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Ribavirin dose reduction did not decrease SVR in patients with HCV

In a Korean cohort, a majority of patients with hepatitis C virus infection treated with a triple combination therapy of Incivek, pegylated interferon and ribavirin achieved a sustained virologic response even after a reduction in ribavirin, according to study data.

“In this study, we assessed the influence of [inosine triphosphatase] polymorphism only in patients who began triple therapy after telaprevir was approved,” the researchers wrote. “This restriction is important because pre-approval clinical trials included mainly younger and nonanemic patients, but patients in Japan tend to be on average 10 years older than in Western countries and include a higher proportion of women, for whom ribavirin-induced anemia is of particular concern.”

Researchers analyzed data of 273 patients with HCV genotype 1 infection who were treated with Incivek (telaprevir, Vertex Pharmaceuticals) plus PEG-IFN a-2b and ribavirin for 24 weeks. Patients received weight-based telaprevir (500 mg or 750 mg) three times a day and all drug amounts were reduced as necessary according to dose reduction guidelines, according to the researchers. Invader assay was used to measure single nucleotide polymorphism genotyping for interferon lambda 4 and inosine triphosphatase (ITPA). Researchers sought to determine any effect of ITPA polymorphism on dose reduction during triple therapy.

Overall, 80.2% of patients (n = 219) achieved an SVR, 9.5% were nonresponders, 5.5% developed viral breakthrough during therapy and 4.8% relapsed during follow-up. Hemoglobin levels reduced at a faster rate among patients prone to anemia with ITPA rs1127354 CC genotype compared with patients with CA or AA genotypes. As a result of the hemoglobin decline, regimen dosages were reduced per treatment guidelines.

Patients with the rs1127354 CC genotype experienced greater ribavirin reduction compared with patients with CT or TT genotype (P = .028). The amount of ribavirin given to patients with rs1127354 CC was lower compared with patients with CA or AA (51,470 mg vs. 63,950 mg; P = .016). However, period reductions for both telaprevir and PEG-IFN were not significantly different among the cohort, according to the research.

The patients who reached SVR had received a greater amount of each drug during therapy compared with patients who did not. All patients who received at least 90% of the original dose of ribavirin achieved SVR and most patients took ribavirin for the entire duration of therapy, which led to an SVR rate of nearly 90% of all patients.

Multivariate analysis showed interferon lambda 4, the number of platelets and PEG-IFN adherence to be independent predictors of SVR.    

Therapy was discontinued in 60 patients due to adverse events of anemia (35%), nonvirological response (15%), malaise (13%), renal damage (12%), among others.

“Postmarketing-phase triple therapy resulted in a high SVR rate in spite of extensive ribavirin dose reduction in a diverse patient population, indicating the importance of treatment continuation and appropriate management of adverse events,” the researchers concluded.

Disclosure: The researchers report no relevant financial disclosures.