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Daclatasvir/simeprevir yielded encouraging outcomes with or without ribavirin
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BOSTON — Combination therapy with daclatasvir and simeprevir plus ribavirin was associated with a 95% 12-week sustained virologic response rate in a cohort of patients with genotype 1b disease, according to findings presented here at the 2014 Conference on Retroviruses and Opportunistic Infections.
The researchers conducted an open-label study to evaluate daclatasvir (Bristol-Myers Squibb) and simeprevir (Olysio, Janssen) with or without ribavirin for safety and efficacy outcomes.
The analysis included 104 treatment-naive patients and 43 previous null responders.
Seventy-six patients received daclastavir 30 mg and simeprevir 150 mg once daily, whereas 71 patients received these two drugs plus weight-based ribavirin.
A second randomization was conducted for duration. A cohort of patients stopped treatment at week 12, and the remainder continued through week 24. An exploratory analysis investigated the 24-week ribavirin-containing regimen in 12 treatment-naive patients and nine null responders, all of whom had genotype 1a disease.
Hepatitis C virus RNA below the assay limit of quantification at 12 weeks served as the primary outcome measure.
All treatment groups were similar in terms of baseline demographics. The cohort was 92% white, 49% men, 21% cirrhotic and 76% IL28B non-CC genotype, according to the study data presented by Christophe Hézode, MD, PhD, a hepatologist at Henri Mondor Hospital in Paris.
Sustained virologic response (SVR) at 12 weeks, as determined by an intention-to-treat analysis, was reported in 84.9% of 53 treatment-naive patients with genotype 1b disease who received the combination without ribavirin and 74.5% of treatment-naive genotype 1b patients who received ribavirin.
Among genotype 1b null responders, the 12-week response was 65% of 23 patients in the non-ribavirin group and 95% of 20 patients who received the ribavirin-containing regimen.
The investigators adjusted the analysis for discontinuation rates before week 12 to determine estimates for 12-week SVR rates. They found that the rates for genotype 1b patients were similar for 12 or 24 weeks of therapy in the naive group but higher after 12 weeks compared with 24 weeks in the null responders.
In the genotype 1a cohort, 66.7% of 12 patients achieved 12-week SVR. Pegylated interferon/ribavirin plus daclatasvir and simeprevir was offered as rescue therapy to null responders, who the investigators counted as treatment failures.
Neurotoxicity and liver disorder were the most frequently reported serious adverse events. One unrelated intracranial hematoma was the only on-treatment fatality reported. Three patients who experienced neurotoxicity, constipation and insomnia discontinued therapy. Grade 3 or 4 total bilirubin elevations without concurrent transaminase elevations were reported in 17 patients, 14 of whom were receiving ribavirin.
The investigators said these events were “consistent with ribavirin-induced hemolysis and known effects of [simeprevir] on bilirubin transporters.” They concluded that daclatasvir and simeprevir were well tolerated with or without ribavirin.
For more information:
Zeuzem S. Abstract #28LB. Presented at: CROI 2014; March 3-6, 2014; Boston.
Disclosure: Hezode reports no relevant financial disclosures.