Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis

Kris V. Kowdley, Stuart C. Gordon, K. Rajender Reddy, Lorenzo Rossaro, David E. Bernstein, Eric Lawitz, Mitchell L. Shiffman, Eugene Schiff, Reem Ghalib, Michael Ryan, Vinod Rustgi, Mario Chojkier, Robert Herring, Adrian M. Di Bisceglie, Paul J. Pockros, G. Mani Subramanian, Di An, Evguenia Svarovskaia, Robert H. Hyland, Phillip S. Pang & 5 others William T. Symonds, John G. McHutchison, Andrew J. Muir, David Pound, Michael W. Fried

Research output: Contribution to journalArticle

Abstract

BACKGROUND: High rates of sustained virologic response were observed among patients with hepatitis C virus (HCV) infection who received 12 weeks of treatment with the nucleotide polymerase inhibitor sofosbuvir combined with the NS5A inhibitor ledipasvir. This study examined 8 weeks of treatment with this regimen. METHODS: In this phase 3, open-label study, we randomly assigned 647 previously untreated patients with HCV genotype 1 infection without cirrhosis to receive ledipasvir and sofosbuvir (ledipasvir-sofosbuvir) for 8 weeks, ledipasvir-sofosbuvir plus ribavirin for 8 weeks, or ledipasvir-sofosbuvir for 12 weeks. The primary end point was sustained virologic response at 12 weeks after the end of therapy. RESULTS: The rate of sustained virologic response was 94% (95% confidence interval [CI], 90 to 97) with 8 weeks of ledipasvir-sofosbuvir, 93% (95% CI, 89 to 96) with 8 weeks of ledipasvir-sofosbuvir plus ribavirin, and 95% (95% CI, 92 to 98) with 12 weeks of ledipasvir-sofosbuvir. As compared with the rate of sustained virologic response in the group that received 8 weeks of ledipasvir-sofosbuvir, the rate in the 12-week group was 1 percentage point higher (97.5% CI, -4 to 6) and the rate in the group that received 8 weeks of ledipasvir-sofosbuvir with ribavirin was 1 percentage point lower (95% CI, -6 to 4); these results indicated noninferiority of the 8-week ledipasvir-sofosbuvir regimen, on the basis of a noninferiority margin of 12 percentage points. Adverse events were more common in the group that received ribavirin than in the other two groups. No patient who received 8 weeks of only ledipasvir-sofosbuvir discontinued treatment owing to adverse events. CONCLUSIONS: Ledipasvir-sofosbuvir for 8 weeks was associated with a high rate of sustained virologic response among previously untreated patients with HCV genotype 1 infection without cirrhosis. No additional benefit was associated with the inclusion of ribavirin in the regimen or with extension of the duration of treatment to 12 weeks.

Original languageEnglish (US)
Pages (from-to)1879-1888
Number of pages10
JournalNew England Journal of Medicine
Volume370
Issue number20
DOIs
StatePublished - 2014
Externally publishedYes

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Chronic Hepatitis C
Hepacivirus
Fibrosis
Ribavirin
Confidence Intervals
sofosbuvir drug combination ledipasvir
Genotype
Therapeutics
Virus Diseases
Infection
Nucleotides
Sustained Virologic Response

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kowdley, K. V., Gordon, S. C., Reddy, K. R., Rossaro, L., Bernstein, D. E., Lawitz, E., ... Fried, M. W. (2014). Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. New England Journal of Medicine, 370(20), 1879-1888. https://doi.org/10.1056/NEJMoa1402355

Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. / Kowdley, Kris V.; Gordon, Stuart C.; Reddy, K. Rajender; Rossaro, Lorenzo; Bernstein, David E.; Lawitz, Eric; Shiffman, Mitchell L.; Schiff, Eugene; Ghalib, Reem; Ryan, Michael; Rustgi, Vinod; Chojkier, Mario; Herring, Robert; Di Bisceglie, Adrian M.; Pockros, Paul J.; Subramanian, G. Mani; An, Di; Svarovskaia, Evguenia; Hyland, Robert H.; Pang, Phillip S.; Symonds, William T.; McHutchison, John G.; Muir, Andrew J.; Pound, David; Fried, Michael W.

In: New England Journal of Medicine, Vol. 370, No. 20, 2014, p. 1879-1888.

Research output: Contribution to journalArticle

Kowdley, KV, Gordon, SC, Reddy, KR, Rossaro, L, Bernstein, DE, Lawitz, E, Shiffman, ML, Schiff, E, Ghalib, R, Ryan, M, Rustgi, V, Chojkier, M, Herring, R, Di Bisceglie, AM, Pockros, PJ, Subramanian, GM, An, D, Svarovskaia, E, Hyland, RH, Pang, PS, Symonds, WT, McHutchison, JG, Muir, AJ, Pound, D & Fried, MW 2014, 'Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis', New England Journal of Medicine, vol. 370, no. 20, pp. 1879-1888. https://doi.org/10.1056/NEJMoa1402355
Kowdley KV, Gordon SC, Reddy KR, Rossaro L, Bernstein DE, Lawitz E et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. New England Journal of Medicine. 2014;370(20):1879-1888. https://doi.org/10.1056/NEJMoa1402355
Kowdley, Kris V. ; Gordon, Stuart C. ; Reddy, K. Rajender ; Rossaro, Lorenzo ; Bernstein, David E. ; Lawitz, Eric ; Shiffman, Mitchell L. ; Schiff, Eugene ; Ghalib, Reem ; Ryan, Michael ; Rustgi, Vinod ; Chojkier, Mario ; Herring, Robert ; Di Bisceglie, Adrian M. ; Pockros, Paul J. ; Subramanian, G. Mani ; An, Di ; Svarovskaia, Evguenia ; Hyland, Robert H. ; Pang, Phillip S. ; Symonds, William T. ; McHutchison, John G. ; Muir, Andrew J. ; Pound, David ; Fried, Michael W. / Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. In: New England Journal of Medicine. 2014 ; Vol. 370, No. 20. pp. 1879-1888.
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abstract = "BACKGROUND: High rates of sustained virologic response were observed among patients with hepatitis C virus (HCV) infection who received 12 weeks of treatment with the nucleotide polymerase inhibitor sofosbuvir combined with the NS5A inhibitor ledipasvir. This study examined 8 weeks of treatment with this regimen. METHODS: In this phase 3, open-label study, we randomly assigned 647 previously untreated patients with HCV genotype 1 infection without cirrhosis to receive ledipasvir and sofosbuvir (ledipasvir-sofosbuvir) for 8 weeks, ledipasvir-sofosbuvir plus ribavirin for 8 weeks, or ledipasvir-sofosbuvir for 12 weeks. The primary end point was sustained virologic response at 12 weeks after the end of therapy. RESULTS: The rate of sustained virologic response was 94{\%} (95{\%} confidence interval [CI], 90 to 97) with 8 weeks of ledipasvir-sofosbuvir, 93{\%} (95{\%} CI, 89 to 96) with 8 weeks of ledipasvir-sofosbuvir plus ribavirin, and 95{\%} (95{\%} CI, 92 to 98) with 12 weeks of ledipasvir-sofosbuvir. As compared with the rate of sustained virologic response in the group that received 8 weeks of ledipasvir-sofosbuvir, the rate in the 12-week group was 1 percentage point higher (97.5{\%} CI, -4 to 6) and the rate in the group that received 8 weeks of ledipasvir-sofosbuvir with ribavirin was 1 percentage point lower (95{\%} CI, -6 to 4); these results indicated noninferiority of the 8-week ledipasvir-sofosbuvir regimen, on the basis of a noninferiority margin of 12 percentage points. Adverse events were more common in the group that received ribavirin than in the other two groups. No patient who received 8 weeks of only ledipasvir-sofosbuvir discontinued treatment owing to adverse events. CONCLUSIONS: Ledipasvir-sofosbuvir for 8 weeks was associated with a high rate of sustained virologic response among previously untreated patients with HCV genotype 1 infection without cirrhosis. No additional benefit was associated with the inclusion of ribavirin in the regimen or with extension of the duration of treatment to 12 weeks.",
author = "Kowdley, {Kris V.} and Gordon, {Stuart C.} and Reddy, {K. Rajender} and Lorenzo Rossaro and Bernstein, {David E.} and Eric Lawitz and Shiffman, {Mitchell L.} and Eugene Schiff and Reem Ghalib and Michael Ryan and Vinod Rustgi and Mario Chojkier and Robert Herring and {Di Bisceglie}, {Adrian M.} and Pockros, {Paul J.} and Subramanian, {G. Mani} and Di An and Evguenia Svarovskaia and Hyland, {Robert H.} and Pang, {Phillip S.} and Symonds, {William T.} and McHutchison, {John G.} and Muir, {Andrew J.} and David Pound and Fried, {Michael W.}",
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TY - JOUR

T1 - Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis

AU - Kowdley, Kris V.

AU - Gordon, Stuart C.

AU - Reddy, K. Rajender

AU - Rossaro, Lorenzo

AU - Bernstein, David E.

AU - Lawitz, Eric

AU - Shiffman, Mitchell L.

AU - Schiff, Eugene

AU - Ghalib, Reem

AU - Ryan, Michael

AU - Rustgi, Vinod

AU - Chojkier, Mario

AU - Herring, Robert

AU - Di Bisceglie, Adrian M.

AU - Pockros, Paul J.

AU - Subramanian, G. Mani

AU - An, Di

AU - Svarovskaia, Evguenia

AU - Hyland, Robert H.

AU - Pang, Phillip S.

AU - Symonds, William T.

AU - McHutchison, John G.

AU - Muir, Andrew J.

AU - Pound, David

AU - Fried, Michael W.

PY - 2014

Y1 - 2014

N2 - BACKGROUND: High rates of sustained virologic response were observed among patients with hepatitis C virus (HCV) infection who received 12 weeks of treatment with the nucleotide polymerase inhibitor sofosbuvir combined with the NS5A inhibitor ledipasvir. This study examined 8 weeks of treatment with this regimen. METHODS: In this phase 3, open-label study, we randomly assigned 647 previously untreated patients with HCV genotype 1 infection without cirrhosis to receive ledipasvir and sofosbuvir (ledipasvir-sofosbuvir) for 8 weeks, ledipasvir-sofosbuvir plus ribavirin for 8 weeks, or ledipasvir-sofosbuvir for 12 weeks. The primary end point was sustained virologic response at 12 weeks after the end of therapy. RESULTS: The rate of sustained virologic response was 94% (95% confidence interval [CI], 90 to 97) with 8 weeks of ledipasvir-sofosbuvir, 93% (95% CI, 89 to 96) with 8 weeks of ledipasvir-sofosbuvir plus ribavirin, and 95% (95% CI, 92 to 98) with 12 weeks of ledipasvir-sofosbuvir. As compared with the rate of sustained virologic response in the group that received 8 weeks of ledipasvir-sofosbuvir, the rate in the 12-week group was 1 percentage point higher (97.5% CI, -4 to 6) and the rate in the group that received 8 weeks of ledipasvir-sofosbuvir with ribavirin was 1 percentage point lower (95% CI, -6 to 4); these results indicated noninferiority of the 8-week ledipasvir-sofosbuvir regimen, on the basis of a noninferiority margin of 12 percentage points. Adverse events were more common in the group that received ribavirin than in the other two groups. No patient who received 8 weeks of only ledipasvir-sofosbuvir discontinued treatment owing to adverse events. CONCLUSIONS: Ledipasvir-sofosbuvir for 8 weeks was associated with a high rate of sustained virologic response among previously untreated patients with HCV genotype 1 infection without cirrhosis. No additional benefit was associated with the inclusion of ribavirin in the regimen or with extension of the duration of treatment to 12 weeks.

AB - BACKGROUND: High rates of sustained virologic response were observed among patients with hepatitis C virus (HCV) infection who received 12 weeks of treatment with the nucleotide polymerase inhibitor sofosbuvir combined with the NS5A inhibitor ledipasvir. This study examined 8 weeks of treatment with this regimen. METHODS: In this phase 3, open-label study, we randomly assigned 647 previously untreated patients with HCV genotype 1 infection without cirrhosis to receive ledipasvir and sofosbuvir (ledipasvir-sofosbuvir) for 8 weeks, ledipasvir-sofosbuvir plus ribavirin for 8 weeks, or ledipasvir-sofosbuvir for 12 weeks. The primary end point was sustained virologic response at 12 weeks after the end of therapy. RESULTS: The rate of sustained virologic response was 94% (95% confidence interval [CI], 90 to 97) with 8 weeks of ledipasvir-sofosbuvir, 93% (95% CI, 89 to 96) with 8 weeks of ledipasvir-sofosbuvir plus ribavirin, and 95% (95% CI, 92 to 98) with 12 weeks of ledipasvir-sofosbuvir. As compared with the rate of sustained virologic response in the group that received 8 weeks of ledipasvir-sofosbuvir, the rate in the 12-week group was 1 percentage point higher (97.5% CI, -4 to 6) and the rate in the group that received 8 weeks of ledipasvir-sofosbuvir with ribavirin was 1 percentage point lower (95% CI, -6 to 4); these results indicated noninferiority of the 8-week ledipasvir-sofosbuvir regimen, on the basis of a noninferiority margin of 12 percentage points. Adverse events were more common in the group that received ribavirin than in the other two groups. No patient who received 8 weeks of only ledipasvir-sofosbuvir discontinued treatment owing to adverse events. CONCLUSIONS: Ledipasvir-sofosbuvir for 8 weeks was associated with a high rate of sustained virologic response among previously untreated patients with HCV genotype 1 infection without cirrhosis. No additional benefit was associated with the inclusion of ribavirin in the regimen or with extension of the duration of treatment to 12 weeks.

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