Efficacy of 8-Week Daclatasvir-Sofosbuvir Regimen for Chronic Hepatitis C

Ahmed N. Farrag, BPharm

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A recent systematic review and meta-analysis assessed the efficacy of an 8-week regimen of daclatasvir (DCV) plus sofosbuvir (SOF) in patients with chronic hepatitis C virus (HCV) infection. The analysis aimed to determine the sustained virologic response at 12 weeks after treatment (SVR12) for this shortened regimen, which is being considered as a potential option for low- and middle-income countries (LMICs) due to the high cost of direct-acting antivirals (DAAs).

The analysis included six studies with a total of 159 patients. The pooled SVR12 rate for the 8-week regimen ranged from 91% to 97%. The pragmatic analysis showed an SVR12 of 97% (95% confidence interval: 91%-100%), while a conservative approach, which took response-guided treatment (RGT) into account, revealed an SVR12 of 93% (95% CI: 84%-95%).

In an exclusive interview with Contagion, Ahmed N. Farrag, BPharm, lead author on the study said, “Our study demonstrates the promise of an 8-week DCV-SOF regimen with an estimated pooled SVR12 rate exceeding 90% across all sensitivity analysis scenarios, suggesting substantial potential for reducing treatment duration and thereby, the associated treatment costs by one third.”

He further emphasized that this reduction could make hepatitis C treatment more accessible in LMICs. Although, Farrag highlighted that while these findings are promising, a head-to-head randomized controlled trial (RCT) comparing the 8-week regimen to the standard 12-week course is essential, “Such a trial will provide definitive evidence needed to inform global health policies and ensure the regimen’s efficacy in broader patient populations.”

The study’s sensitivity analyses accounted for potential confounders, including comorbidities such as HIV and cirrhosis, as well as the use of the RGT approach, where only patients who achieved rapid virologic response (RVR) were assigned to the 8-week course. Farrag stated, “Statistically speaking, our confidence arises from the 95% confidence level for the predicted intervals for the pooled SVR12 rates as per our meta-analysis. Nonetheless, translating these findings into real-world settings, which encompass diverse patient populations including those with comorbidities or those who are treatment-experienced, presents additional challenges.”

Despite these adjustments, he noted that real-world effectiveness would require further evaluation, “Real-world “effectiveness” from different clinical settings would present a more comprehensive perspective on these confounders.”

In discussing the potential barriers to widespread adoption of the 8-week regimen, Farrag identified challenges, “Clinically: Identifying patients suitable for the shorter regimen is crucial. For instance, patients with cirrhosis and those with HIV co-infection who typically won’t be eligible for the shortened regimen.”

He continued to explain, “Economically: While the 8-week regimen potentially reduces treatment costs, possible anticipated treatment failures and the consequent need for retreatment are essential considerations.”

Farrag also highlighted the importance of pharmacoeconomic studies in evaluating the cost-effectiveness of the regimen. “Although several studies indicated that patients who did not achieve SVR12 following standard or short courses of direct-acting antivirals achieved high cure rates when retreated, pharmacoeconomic studies including cost-effectiveness and cost-benefit analyses, specifically, from payer perspectives, are required. These studies are expected to account for the upfront savings and the downstream costs of retreatment.”

Farrag concludes, “while the high efficacy of the 8-week DCV-SOF regimen is promising, its widespread adoption will benefit from further validation through head-to-head clinical trials and a thorough pharmacoeconomic analysis, considering potential retreatments for those who experience treatment failures.”

Reference

Farrag AN, Kamel AM. Efficacy of 8-week daclatasvir-sofosbuvir regimen in chronic hepatitis C: a systematic review and meta-analysis. Virol J. 2024;21:275. November 4, 2024. Accessed November 13, 2024. https://doi.org/10.1186/s12985-024-02544-2