Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis

M. P. Curry, J. G. O'Leary, N. Bzowej, A. J. Muir, K. M. Korenblat, J. M. Fenkel, K. R. Reddy, E. Lawitz, S. L. Flamm, T. Schiano, L. Teperman, R. Fontana, E. Schiff, M. Fried, B. Doehle, D. An, J. McNally, A. Osinusi, D. M. Brainard, J. G. McHutchisonR. S. Brown, M. Charlton

Research output: Contribution to journalArticle

395 Citations (Scopus)

Abstract

BACKGROUND As the population that is infected with the hepatitis C virus (HCV) ages, the number of patients with decompensated cirrhosis is expected to increase. METHODS We conducted a phase 3, open-label study involving both previously treated and previously untreated patients infected with HCV genotypes 1 through 6 who had decompensated cirrhosis (classified as Child-Pugh-Turcotte class B). Patients were randomly assigned in a 1:1:1 ratio to receive the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir once daily for 12 weeks, sofosbuvir- velpatasvir plus ribavirin for 12 weeks, or sofosbuvir-velpatasvir for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. RESULTS Of the 267 patients who received treatment, 78% had HCV genotype 1, 4% genotype 2, 15% genotype 3, 3% genotype 4, and less than 1% genotype 6; no patients had genotype 5. Overall rates of sustained virologic response were 83% (95% confidence interval [CI], 74 to 90) among patients who received 12 weeks of sofosbuvir- velpatasvir, 94% (95% CI, 87 to 98) among those who received 12 weeks of sofosbuvir-velpatasvir plus ribavirin, and 86% (95% CI, 77 to 92) among those who received 24 weeks of sofosbuvir-velpatasvir. Post hoc analysis did not detect any significant differences in rates of sustained virologic response among the three study groups. Serious adverse events occurred in 19% of patients who received 12 weeks of sofosbuvir-velpatasvir, 16% of those who received 12 weeks of sofosbuvir-velpatasvir plus ribavirin, and 18% of those who received 24 weeks of sofosbuvir-velpatasvir. The most common adverse events were fatigue (29%), nausea (23%), and headache (22%) in all patients and anemia (31%) in the patients receiving ribavirin. CONCLUSIONS Treatment with sofosbuvir-velpatasvir with or without ribavirin for 12 weeks and with sofosbuvir-velpatasvir for 24 weeks resulted in high rates of sustained virologic response in patients with HCV infection and decompensated cirrhosis. (Funded by Gilead Sciences; ASTRAL-4 ClinicalTrials.gov number, NCT02201901.)

Original languageEnglish (US)
Pages (from-to)2618-2628
Number of pages11
JournalNew England Journal of Medicine
Volume373
Issue number27
DOIs
StatePublished - Dec 31 2015
Externally publishedYes

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Hepacivirus
Fibrosis
Ribavirin
Genotype
Confidence Intervals
Sofosbuvir
velpatasvir
Virus Diseases
Nausea
Fatigue
Headache
Anemia
Therapeutics
Nucleotides
Sustained Virologic Response

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Curry, M. P., O'Leary, J. G., Bzowej, N., Muir, A. J., Korenblat, K. M., Fenkel, J. M., ... Charlton, M. (2015). Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. New England Journal of Medicine, 373(27), 2618-2628. https://doi.org/10.1056/NEJMoa1512614

Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. / Curry, M. P.; O'Leary, J. G.; Bzowej, N.; Muir, A. J.; Korenblat, K. M.; Fenkel, J. M.; Reddy, K. R.; Lawitz, E.; Flamm, S. L.; Schiano, T.; Teperman, L.; Fontana, R.; Schiff, E.; Fried, M.; Doehle, B.; An, D.; McNally, J.; Osinusi, A.; Brainard, D. M.; McHutchison, J. G.; Brown, R. S.; Charlton, M.

In: New England Journal of Medicine, Vol. 373, No. 27, 31.12.2015, p. 2618-2628.

Research output: Contribution to journalArticle

Curry, MP, O'Leary, JG, Bzowej, N, Muir, AJ, Korenblat, KM, Fenkel, JM, Reddy, KR, Lawitz, E, Flamm, SL, Schiano, T, Teperman, L, Fontana, R, Schiff, E, Fried, M, Doehle, B, An, D, McNally, J, Osinusi, A, Brainard, DM, McHutchison, JG, Brown, RS & Charlton, M 2015, 'Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis', New England Journal of Medicine, vol. 373, no. 27, pp. 2618-2628. https://doi.org/10.1056/NEJMoa1512614
Curry MP, O'Leary JG, Bzowej N, Muir AJ, Korenblat KM, Fenkel JM et al. Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. New England Journal of Medicine. 2015 Dec 31;373(27):2618-2628. https://doi.org/10.1056/NEJMoa1512614
Curry, M. P. ; O'Leary, J. G. ; Bzowej, N. ; Muir, A. J. ; Korenblat, K. M. ; Fenkel, J. M. ; Reddy, K. R. ; Lawitz, E. ; Flamm, S. L. ; Schiano, T. ; Teperman, L. ; Fontana, R. ; Schiff, E. ; Fried, M. ; Doehle, B. ; An, D. ; McNally, J. ; Osinusi, A. ; Brainard, D. M. ; McHutchison, J. G. ; Brown, R. S. ; Charlton, M. / Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. In: New England Journal of Medicine. 2015 ; Vol. 373, No. 27. pp. 2618-2628.
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abstract = "BACKGROUND As the population that is infected with the hepatitis C virus (HCV) ages, the number of patients with decompensated cirrhosis is expected to increase. METHODS We conducted a phase 3, open-label study involving both previously treated and previously untreated patients infected with HCV genotypes 1 through 6 who had decompensated cirrhosis (classified as Child-Pugh-Turcotte class B). Patients were randomly assigned in a 1:1:1 ratio to receive the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir once daily for 12 weeks, sofosbuvir- velpatasvir plus ribavirin for 12 weeks, or sofosbuvir-velpatasvir for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. RESULTS Of the 267 patients who received treatment, 78{\%} had HCV genotype 1, 4{\%} genotype 2, 15{\%} genotype 3, 3{\%} genotype 4, and less than 1{\%} genotype 6; no patients had genotype 5. Overall rates of sustained virologic response were 83{\%} (95{\%} confidence interval [CI], 74 to 90) among patients who received 12 weeks of sofosbuvir- velpatasvir, 94{\%} (95{\%} CI, 87 to 98) among those who received 12 weeks of sofosbuvir-velpatasvir plus ribavirin, and 86{\%} (95{\%} CI, 77 to 92) among those who received 24 weeks of sofosbuvir-velpatasvir. Post hoc analysis did not detect any significant differences in rates of sustained virologic response among the three study groups. Serious adverse events occurred in 19{\%} of patients who received 12 weeks of sofosbuvir-velpatasvir, 16{\%} of those who received 12 weeks of sofosbuvir-velpatasvir plus ribavirin, and 18{\%} of those who received 24 weeks of sofosbuvir-velpatasvir. The most common adverse events were fatigue (29{\%}), nausea (23{\%}), and headache (22{\%}) in all patients and anemia (31{\%}) in the patients receiving ribavirin. CONCLUSIONS Treatment with sofosbuvir-velpatasvir with or without ribavirin for 12 weeks and with sofosbuvir-velpatasvir for 24 weeks resulted in high rates of sustained virologic response in patients with HCV infection and decompensated cirrhosis. (Funded by Gilead Sciences; ASTRAL-4 ClinicalTrials.gov number, NCT02201901.)",
author = "Curry, {M. P.} and O'Leary, {J. G.} and N. Bzowej and Muir, {A. J.} and Korenblat, {K. M.} and Fenkel, {J. M.} and Reddy, {K. R.} and E. Lawitz and Flamm, {S. L.} and T. Schiano and L. Teperman and R. Fontana and E. Schiff and M. Fried and B. Doehle and D. An and J. McNally and A. Osinusi and Brainard, {D. M.} and McHutchison, {J. G.} and Brown, {R. S.} and M. Charlton",
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TY - JOUR

T1 - Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis

AU - Curry, M. P.

AU - O'Leary, J. G.

AU - Bzowej, N.

AU - Muir, A. J.

AU - Korenblat, K. M.

AU - Fenkel, J. M.

AU - Reddy, K. R.

AU - Lawitz, E.

AU - Flamm, S. L.

AU - Schiano, T.

AU - Teperman, L.

AU - Fontana, R.

AU - Schiff, E.

AU - Fried, M.

AU - Doehle, B.

AU - An, D.

AU - McNally, J.

AU - Osinusi, A.

AU - Brainard, D. M.

AU - McHutchison, J. G.

AU - Brown, R. S.

AU - Charlton, M.

PY - 2015/12/31

Y1 - 2015/12/31

N2 - BACKGROUND As the population that is infected with the hepatitis C virus (HCV) ages, the number of patients with decompensated cirrhosis is expected to increase. METHODS We conducted a phase 3, open-label study involving both previously treated and previously untreated patients infected with HCV genotypes 1 through 6 who had decompensated cirrhosis (classified as Child-Pugh-Turcotte class B). Patients were randomly assigned in a 1:1:1 ratio to receive the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir once daily for 12 weeks, sofosbuvir- velpatasvir plus ribavirin for 12 weeks, or sofosbuvir-velpatasvir for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. RESULTS Of the 267 patients who received treatment, 78% had HCV genotype 1, 4% genotype 2, 15% genotype 3, 3% genotype 4, and less than 1% genotype 6; no patients had genotype 5. Overall rates of sustained virologic response were 83% (95% confidence interval [CI], 74 to 90) among patients who received 12 weeks of sofosbuvir- velpatasvir, 94% (95% CI, 87 to 98) among those who received 12 weeks of sofosbuvir-velpatasvir plus ribavirin, and 86% (95% CI, 77 to 92) among those who received 24 weeks of sofosbuvir-velpatasvir. Post hoc analysis did not detect any significant differences in rates of sustained virologic response among the three study groups. Serious adverse events occurred in 19% of patients who received 12 weeks of sofosbuvir-velpatasvir, 16% of those who received 12 weeks of sofosbuvir-velpatasvir plus ribavirin, and 18% of those who received 24 weeks of sofosbuvir-velpatasvir. The most common adverse events were fatigue (29%), nausea (23%), and headache (22%) in all patients and anemia (31%) in the patients receiving ribavirin. CONCLUSIONS Treatment with sofosbuvir-velpatasvir with or without ribavirin for 12 weeks and with sofosbuvir-velpatasvir for 24 weeks resulted in high rates of sustained virologic response in patients with HCV infection and decompensated cirrhosis. (Funded by Gilead Sciences; ASTRAL-4 ClinicalTrials.gov number, NCT02201901.)

AB - BACKGROUND As the population that is infected with the hepatitis C virus (HCV) ages, the number of patients with decompensated cirrhosis is expected to increase. METHODS We conducted a phase 3, open-label study involving both previously treated and previously untreated patients infected with HCV genotypes 1 through 6 who had decompensated cirrhosis (classified as Child-Pugh-Turcotte class B). Patients were randomly assigned in a 1:1:1 ratio to receive the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir once daily for 12 weeks, sofosbuvir- velpatasvir plus ribavirin for 12 weeks, or sofosbuvir-velpatasvir for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. RESULTS Of the 267 patients who received treatment, 78% had HCV genotype 1, 4% genotype 2, 15% genotype 3, 3% genotype 4, and less than 1% genotype 6; no patients had genotype 5. Overall rates of sustained virologic response were 83% (95% confidence interval [CI], 74 to 90) among patients who received 12 weeks of sofosbuvir- velpatasvir, 94% (95% CI, 87 to 98) among those who received 12 weeks of sofosbuvir-velpatasvir plus ribavirin, and 86% (95% CI, 77 to 92) among those who received 24 weeks of sofosbuvir-velpatasvir. Post hoc analysis did not detect any significant differences in rates of sustained virologic response among the three study groups. Serious adverse events occurred in 19% of patients who received 12 weeks of sofosbuvir-velpatasvir, 16% of those who received 12 weeks of sofosbuvir-velpatasvir plus ribavirin, and 18% of those who received 24 weeks of sofosbuvir-velpatasvir. The most common adverse events were fatigue (29%), nausea (23%), and headache (22%) in all patients and anemia (31%) in the patients receiving ribavirin. CONCLUSIONS Treatment with sofosbuvir-velpatasvir with or without ribavirin for 12 weeks and with sofosbuvir-velpatasvir for 24 weeks resulted in high rates of sustained virologic response in patients with HCV infection and decompensated cirrhosis. (Funded by Gilead Sciences; ASTRAL-4 ClinicalTrials.gov number, NCT02201901.)

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