Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options

Ira M. Jacobson, Stuart C. Gordon, Kris V. Kowdley, Eric M. Yoshida, Maribel Rodriguez-Torres, Mark S. Sulkowski, Mitchell L. Shiffman, Eric Lawitz, Gregory Everson, Michael Bennett, Eugene R Schiff, M. Tarek Al-Assi, G. Mani Subramanian, Di An, Ming Lin, John McNally, Diana Brainard, William T. Symonds, John G. McHutchison, Keyur PatelJordan Feld, Stephen Pianko, David R. Nelson

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3 for whom treatment with peginterferon is not an option, or who have not had a response to prior interferon treatment, currently have no approved treatment options. In phase 2 trials, regimens including the oral nucleotide polymerase inhibitor sofosbuvir have shown efficacy in patients with HCV genotype 2 or 3 infection. METHODS: We conducted two randomized, phase 3 studies involving patients with chronic HCV genotype 2 or 3 infection. In one trial, patients for whom treatment with peginterferon was not an option received oral sofosbuvir and ribavirin (207 patients) or matching placebo (71) for 12 weeks. In a second trial, patients who had not had a response to prior interferon therapy received sofosbuvir and ribavirin for 12 weeks (103 patients) or 16 weeks (98). The primary end point was a sustained virologic response at 12 weeks after therapy. RESULTS: Among patients for whom treatment with peginterferon was not an option, the rate of a sustained virologic response was 78% (95% confidence interval [CI], 72 to 83) with sofosbuvir and ribavirin, as compared with 0% with placebo (P<0.001). Among previously treated patients, the rate of response was 50% with 12 weeks of treatment, as compared with 73% with 16 weeks of treatment (difference, -23 percentage points; 95% CI, -35 to -11; P<0.001). In both studies, response rates were lower among patients with genotype 3 infection than among those with genotype 2 infection and, among patients with genotype 3 infection, lower among those with cirrhosis than among those without cirrhosis. The most common adverse events were headache, fatigue, nausea, and insomnia; the overall rate of discontinuation of sofosbuvir was low (1 to 2%). CONCLUSIONS: In patients with HCV genotype 2 or 3 infection for whom treatment with peginterferon and ribavirin was not an option, 12 or 16 weeks of treatment with sofosbuvir and ribavirin was effective. Efficacy was increased among patients with HCV genotype 2 infection and those without cirrhosis. In previously treated patients with genotype 3 infection, 16 weeks of therapy was significantly more effective than 12 weeks. (Funded by Gilead Sciences; POSITRON and FUSION ClinicalTrials.gov numbers, NCT01542788 and NCT01604850, respectively.)

Original languageEnglish
Pages (from-to)1867-1877
Number of pages11
JournalNew England Journal of Medicine
Volume368
Issue number20
DOIs
StatePublished - May 16 2013

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Hepatitis C
Genotype
Ribavirin
Hepacivirus
Infection
Therapeutics
Fibrosis
Sofosbuvir
Interferons
Placebos
Confidence Intervals
Sleep Initiation and Maintenance Disorders
Chronic Hepatitis C
Nausea
Fatigue
Headache
Nucleotides

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Jacobson, I. M., Gordon, S. C., Kowdley, K. V., Yoshida, E. M., Rodriguez-Torres, M., Sulkowski, M. S., ... Nelson, D. R. (2013). Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. New England Journal of Medicine, 368(20), 1867-1877. https://doi.org/10.1056/NEJMoa1214854

Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. / Jacobson, Ira M.; Gordon, Stuart C.; Kowdley, Kris V.; Yoshida, Eric M.; Rodriguez-Torres, Maribel; Sulkowski, Mark S.; Shiffman, Mitchell L.; Lawitz, Eric; Everson, Gregory; Bennett, Michael; Schiff, Eugene R; Al-Assi, M. Tarek; Subramanian, G. Mani; An, Di; Lin, Ming; McNally, John; Brainard, Diana; Symonds, William T.; McHutchison, John G.; Patel, Keyur; Feld, Jordan; Pianko, Stephen; Nelson, David R.

In: New England Journal of Medicine, Vol. 368, No. 20, 16.05.2013, p. 1867-1877.

Research output: Contribution to journalArticle

Jacobson, IM, Gordon, SC, Kowdley, KV, Yoshida, EM, Rodriguez-Torres, M, Sulkowski, MS, Shiffman, ML, Lawitz, E, Everson, G, Bennett, M, Schiff, ER, Al-Assi, MT, Subramanian, GM, An, D, Lin, M, McNally, J, Brainard, D, Symonds, WT, McHutchison, JG, Patel, K, Feld, J, Pianko, S & Nelson, DR 2013, 'Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options', New England Journal of Medicine, vol. 368, no. 20, pp. 1867-1877. https://doi.org/10.1056/NEJMoa1214854
Jacobson IM, Gordon SC, Kowdley KV, Yoshida EM, Rodriguez-Torres M, Sulkowski MS et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. New England Journal of Medicine. 2013 May 16;368(20):1867-1877. https://doi.org/10.1056/NEJMoa1214854
Jacobson, Ira M. ; Gordon, Stuart C. ; Kowdley, Kris V. ; Yoshida, Eric M. ; Rodriguez-Torres, Maribel ; Sulkowski, Mark S. ; Shiffman, Mitchell L. ; Lawitz, Eric ; Everson, Gregory ; Bennett, Michael ; Schiff, Eugene R ; Al-Assi, M. Tarek ; Subramanian, G. Mani ; An, Di ; Lin, Ming ; McNally, John ; Brainard, Diana ; Symonds, William T. ; McHutchison, John G. ; Patel, Keyur ; Feld, Jordan ; Pianko, Stephen ; Nelson, David R. / Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. In: New England Journal of Medicine. 2013 ; Vol. 368, No. 20. pp. 1867-1877.
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abstract = "BACKGROUND: Patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3 for whom treatment with peginterferon is not an option, or who have not had a response to prior interferon treatment, currently have no approved treatment options. In phase 2 trials, regimens including the oral nucleotide polymerase inhibitor sofosbuvir have shown efficacy in patients with HCV genotype 2 or 3 infection. METHODS: We conducted two randomized, phase 3 studies involving patients with chronic HCV genotype 2 or 3 infection. In one trial, patients for whom treatment with peginterferon was not an option received oral sofosbuvir and ribavirin (207 patients) or matching placebo (71) for 12 weeks. In a second trial, patients who had not had a response to prior interferon therapy received sofosbuvir and ribavirin for 12 weeks (103 patients) or 16 weeks (98). The primary end point was a sustained virologic response at 12 weeks after therapy. RESULTS: Among patients for whom treatment with peginterferon was not an option, the rate of a sustained virologic response was 78{\%} (95{\%} confidence interval [CI], 72 to 83) with sofosbuvir and ribavirin, as compared with 0{\%} with placebo (P<0.001). Among previously treated patients, the rate of response was 50{\%} with 12 weeks of treatment, as compared with 73{\%} with 16 weeks of treatment (difference, -23 percentage points; 95{\%} CI, -35 to -11; P<0.001). In both studies, response rates were lower among patients with genotype 3 infection than among those with genotype 2 infection and, among patients with genotype 3 infection, lower among those with cirrhosis than among those without cirrhosis. The most common adverse events were headache, fatigue, nausea, and insomnia; the overall rate of discontinuation of sofosbuvir was low (1 to 2{\%}). CONCLUSIONS: In patients with HCV genotype 2 or 3 infection for whom treatment with peginterferon and ribavirin was not an option, 12 or 16 weeks of treatment with sofosbuvir and ribavirin was effective. Efficacy was increased among patients with HCV genotype 2 infection and those without cirrhosis. In previously treated patients with genotype 3 infection, 16 weeks of therapy was significantly more effective than 12 weeks. (Funded by Gilead Sciences; POSITRON and FUSION ClinicalTrials.gov numbers, NCT01542788 and NCT01604850, respectively.)",
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T1 - Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options

AU - Jacobson, Ira M.

AU - Gordon, Stuart C.

AU - Kowdley, Kris V.

AU - Yoshida, Eric M.

AU - Rodriguez-Torres, Maribel

AU - Sulkowski, Mark S.

AU - Shiffman, Mitchell L.

AU - Lawitz, Eric

AU - Everson, Gregory

AU - Bennett, Michael

AU - Schiff, Eugene R

AU - Al-Assi, M. Tarek

AU - Subramanian, G. Mani

AU - An, Di

AU - Lin, Ming

AU - McNally, John

AU - Brainard, Diana

AU - Symonds, William T.

AU - McHutchison, John G.

AU - Patel, Keyur

AU - Feld, Jordan

AU - Pianko, Stephen

AU - Nelson, David R.

PY - 2013/5/16

Y1 - 2013/5/16

N2 - BACKGROUND: Patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3 for whom treatment with peginterferon is not an option, or who have not had a response to prior interferon treatment, currently have no approved treatment options. In phase 2 trials, regimens including the oral nucleotide polymerase inhibitor sofosbuvir have shown efficacy in patients with HCV genotype 2 or 3 infection. METHODS: We conducted two randomized, phase 3 studies involving patients with chronic HCV genotype 2 or 3 infection. In one trial, patients for whom treatment with peginterferon was not an option received oral sofosbuvir and ribavirin (207 patients) or matching placebo (71) for 12 weeks. In a second trial, patients who had not had a response to prior interferon therapy received sofosbuvir and ribavirin for 12 weeks (103 patients) or 16 weeks (98). The primary end point was a sustained virologic response at 12 weeks after therapy. RESULTS: Among patients for whom treatment with peginterferon was not an option, the rate of a sustained virologic response was 78% (95% confidence interval [CI], 72 to 83) with sofosbuvir and ribavirin, as compared with 0% with placebo (P<0.001). Among previously treated patients, the rate of response was 50% with 12 weeks of treatment, as compared with 73% with 16 weeks of treatment (difference, -23 percentage points; 95% CI, -35 to -11; P<0.001). In both studies, response rates were lower among patients with genotype 3 infection than among those with genotype 2 infection and, among patients with genotype 3 infection, lower among those with cirrhosis than among those without cirrhosis. The most common adverse events were headache, fatigue, nausea, and insomnia; the overall rate of discontinuation of sofosbuvir was low (1 to 2%). CONCLUSIONS: In patients with HCV genotype 2 or 3 infection for whom treatment with peginterferon and ribavirin was not an option, 12 or 16 weeks of treatment with sofosbuvir and ribavirin was effective. Efficacy was increased among patients with HCV genotype 2 infection and those without cirrhosis. In previously treated patients with genotype 3 infection, 16 weeks of therapy was significantly more effective than 12 weeks. (Funded by Gilead Sciences; POSITRON and FUSION ClinicalTrials.gov numbers, NCT01542788 and NCT01604850, respectively.)

AB - BACKGROUND: Patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3 for whom treatment with peginterferon is not an option, or who have not had a response to prior interferon treatment, currently have no approved treatment options. In phase 2 trials, regimens including the oral nucleotide polymerase inhibitor sofosbuvir have shown efficacy in patients with HCV genotype 2 or 3 infection. METHODS: We conducted two randomized, phase 3 studies involving patients with chronic HCV genotype 2 or 3 infection. In one trial, patients for whom treatment with peginterferon was not an option received oral sofosbuvir and ribavirin (207 patients) or matching placebo (71) for 12 weeks. In a second trial, patients who had not had a response to prior interferon therapy received sofosbuvir and ribavirin for 12 weeks (103 patients) or 16 weeks (98). The primary end point was a sustained virologic response at 12 weeks after therapy. RESULTS: Among patients for whom treatment with peginterferon was not an option, the rate of a sustained virologic response was 78% (95% confidence interval [CI], 72 to 83) with sofosbuvir and ribavirin, as compared with 0% with placebo (P<0.001). Among previously treated patients, the rate of response was 50% with 12 weeks of treatment, as compared with 73% with 16 weeks of treatment (difference, -23 percentage points; 95% CI, -35 to -11; P<0.001). In both studies, response rates were lower among patients with genotype 3 infection than among those with genotype 2 infection and, among patients with genotype 3 infection, lower among those with cirrhosis than among those without cirrhosis. The most common adverse events were headache, fatigue, nausea, and insomnia; the overall rate of discontinuation of sofosbuvir was low (1 to 2%). CONCLUSIONS: In patients with HCV genotype 2 or 3 infection for whom treatment with peginterferon and ribavirin was not an option, 12 or 16 weeks of treatment with sofosbuvir and ribavirin was effective. Efficacy was increased among patients with HCV genotype 2 infection and those without cirrhosis. In previously treated patients with genotype 3 infection, 16 weeks of therapy was significantly more effective than 12 weeks. (Funded by Gilead Sciences; POSITRON and FUSION ClinicalTrials.gov numbers, NCT01542788 and NCT01604850, respectively.)

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