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A fixed-dose combination of ledipasvir and sofosbuvir ± ribavirin for treatment of hepatitis C infection: a systematic review and meta-analysis

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Abstract

Background

Novel antivirals have shown promising results in the treatment of hepatitis C. Our objective was to perform a meta-analysis of the efficacy and safety of a fixed-dose combination (FDC) of ledipasvir + sofosbuvir and compare outcomes with the addition of ribavirin (RBV) to treatment with the FDC.

Methods

We searched PubMed, EMBASE, and Cochrane CENTRAL from inception through to 9 February 2017. We used a random effects model to calculate untransformed proportions (PRs) and pooled odds ratios (ORs) with 95% confidence intervals (CIs) to compare outcome measures [sustained virologic response at 12 weeks after treatment completion (SVR12); any, serious, and individual adverse events] between groups receiving the FDC ± RBV. We performed the systematic review according to PRISMA guidelines.

Results

A total of 21 studies with 3826 patients were included in the meta-analysis. Ledipasvir/sofosbuvir was effective in achieving SVR12 after 8 weeks of therapy in genotype (GT) 1 treatment-naïve patients without cirrhosis (PR 0.941; 95% CI 0.910–0.971; p < 0.001; I 2 = 0%). Similarly, it was effective after 12 weeks of therapy in GT1a and 1b patients irrespective of baseline viral load, presence of cirrhosis and CC interleukin-28B (IL28B) GT status. The SVR12 results after 12 weeks of therapy in GT1 patients were similar in groups ± RBV [PR 0.968 (95% CI 0.952–0.985), p < 0.001, I 2 = 46%, and PR 0.973 (95% CI 0.958–0.988), p < 0.001, I 2 = 64%, respectively]. Meta-analysis of comparative studies showed no benefit of adding RBV to ledipasvir/sofosbuvir in achieving SVR12 after 12 weeks of treatment in GT1 patients [OR 1.44 (95% CI 0.34–6.07); p = 0.62; I 2 = 57%], irrespective of cirrhosis.

Conclusion

Twelve weeks of ledipasvir/sofosbuvir is effective in the treatment of GT1a and 1b patients, including those with cirrhosis and difficult to treat non-CC IL28B GTs, and addition of RBV does not confer any benefit in these patients. Eight weeks of ledipasvir/sofosbuvir therapy alone may be sufficient in treatment-naïve GT1 patients without cirrhosis.

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Authors and Affiliations

  1. Department of Rheumatology, Washington Hospital Center, 110 Irving Street, NW, Room 2A-66, Washington, DC, 20010-2975, USA

    Sumit Kunwar

  2. Division of Hospital Medicine, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA

    Ashok Raj Devkota

  3. Department of Medicine, Interfaith Medical Center, Brooklyn, NY, USA

    Dipesh K. C. Ghimire

  4. Division of Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Prabhat Adhikari

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  1. Sumit Kunwar
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Author contribution

SK had full access to all of the data in the study and takes full responsibility for the integrity of the data and accuracy of the data analysis. Study concept and design: SK, AD, DG, PA Acquisition and interpretation of data: SK, AD, DG, PA Statistical analysis: SK Manuscript preparation: SK, AD Critical revision of the manuscript for important intellectual content: DG, PA.

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Correspondence to Sumit Kunwar.

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Authors S.K., A.D., D.G., and P.A. declare no conflict of interest.

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This article does not contain any studies with animals or human participants performed directly by any of its authors.

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Kunwar, S., Devkota, A.R., Ghimire, D.K.C. et al. A fixed-dose combination of ledipasvir and sofosbuvir ± ribavirin for treatment of hepatitis C infection: a systematic review and meta-analysis. Drugs Ther Perspect 33, 348–360 (2017). https://doi.org/10.1007/s40267-017-0401-2

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