Elbasvir-grazoprevir to treat hepatitis C virus infection in persons receiving opioid agonist therapy a randomized trial

Gregory J. Dore, Frederick Altice, Alain H. Litwin, Olav Dalgard, Edward J. Gane, Oren Shibolet, Anne Luetkemeyer, Ronald Nahass, Cheng Yuan Peng, Brian Conway, Jason Grebely, Anita Y M Howe, Isaias N. Gendrano, Erluo Chen, Hsueh Cheng Huang, Frank J. Dutko, David C. Nickle, Bach Yen Nguyen, Janice Wahl, Eliav Barr & 2 others Michael N. Robertson, Heather L. Platt

Research output: Contribution to journalArticle

160 Citations (Scopus)

Abstract

Background: Hepatitis C virus (HCV) infection is common in persons who inject drugs (PWID). Objective: To evaluate elbasvir-grazoprevir in treating HCV infection in PWID. Design: Randomized, placebo-controlled, double-blind trial. (ClinicalTrials.gov: NCT02105688) Setting: Australia, Canada, France, Germany, Israel, the Netherlands, New Zealand, Norway, Spain, Taiwan, the United Kingdom, and the United States. Patients: 301 treatment-naive patients with chronic HCV genotype 1, 4, or 6 infection who were at least 80% adherent to visits for opioid agonist therapy (OAT). Intervention: The immediate-treatment group (ITG) received elbasvir-grazoprevir for 12 weeks; the deferred-treatment group (DTG) received placebo for 12 weeks, no treatment for 4 weeks, then open-label elbasvir-grazoprevir for 12 weeks. Measurements: The primary outcome was sustained virologic response at 12 weeks (SVR12), evaluated separately in the ITG and DTG. Other outcomes included SVR24, viral recurrence or reinfection, and adverse events. Results: The SVR12 was 91.5% (95% CI, 86.8% to 95.0%) in the ITG and 89.5% (95% CI, 81.5% to 94.8%) in the active phase of the DTG. Drug use at baseline and during treatment did not affect SVR12 or adherence to HCV therapy. Among 18 patients with posttreatment viral recurrence through 24-week follow-up, 6 had probable reinfection. If the probable reinfections were assumed to be responses, SVR12 was 94.0% (CI, 89.8% to 96.9%) in the ITG. One patient in the ITG (1 of 201) and 1 in the placebophase DTG (1 of 100) discontinued treatment because of an adverse event. Limitation: These findings may not be generalizable to PWID who are not receiving OAT, nor do they apply to persons with genotype 3 infection, a common strain in PWID. Conclusion: Patients with HCV infection who were receiving OAT and treated with elbasvir-grazoprevir had high rates of SVR12, regardless of ongoing drug use. These results support the removal of drug use as a barrier to interferon-free HCV treatment for patients receiving OAT.

Original languageEnglish (US)
Pages (from-to)625-634
Number of pages10
JournalAnnals of Internal Medicine
Volume165
Issue number9
DOIs
StatePublished - Nov 1 2016

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Virus Diseases
Hepacivirus
Opioid Analgesics
Therapeutics
Pharmaceutical Preparations
MK-5172
2-(pyrrolidin-2-yl)-5-(2-(4-(5-(pyrrolidin-2-yl)-1H-imidazol-2-yl)phenyl)benzofuran-5-yl)-1H-imidazole
Genotype
Placebos
Recurrence
Chronic Hepatitis C
Israel
Norway
Infection

ASJC Scopus subject areas

  • Internal Medicine

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Dore, G. J., Altice, F., Litwin, A. H., Dalgard, O., Gane, E. J., Shibolet, O., ... Platt, H. L. (2016). Elbasvir-grazoprevir to treat hepatitis C virus infection in persons receiving opioid agonist therapy a randomized trial. Annals of Internal Medicine, 165(9), 625-634. https://doi.org/10.7326/M16-0816

Elbasvir-grazoprevir to treat hepatitis C virus infection in persons receiving opioid agonist therapy a randomized trial. / Dore, Gregory J.; Altice, Frederick; Litwin, Alain H.; Dalgard, Olav; Gane, Edward J.; Shibolet, Oren; Luetkemeyer, Anne; Nahass, Ronald; Peng, Cheng Yuan; Conway, Brian; Grebely, Jason; Howe, Anita Y M; Gendrano, Isaias N.; Chen, Erluo; Huang, Hsueh Cheng; Dutko, Frank J.; Nickle, David C.; Nguyen, Bach Yen; Wahl, Janice; Barr, Eliav; Robertson, Michael N.; Platt, Heather L.

In: Annals of Internal Medicine, Vol. 165, No. 9, 01.11.2016, p. 625-634.

Research output: Contribution to journalArticle

Dore, GJ, Altice, F, Litwin, AH, Dalgard, O, Gane, EJ, Shibolet, O, Luetkemeyer, A, Nahass, R, Peng, CY, Conway, B, Grebely, J, Howe, AYM, Gendrano, IN, Chen, E, Huang, HC, Dutko, FJ, Nickle, DC, Nguyen, BY, Wahl, J, Barr, E, Robertson, MN & Platt, HL 2016, 'Elbasvir-grazoprevir to treat hepatitis C virus infection in persons receiving opioid agonist therapy a randomized trial', Annals of Internal Medicine, vol. 165, no. 9, pp. 625-634. https://doi.org/10.7326/M16-0816
Dore, Gregory J. ; Altice, Frederick ; Litwin, Alain H. ; Dalgard, Olav ; Gane, Edward J. ; Shibolet, Oren ; Luetkemeyer, Anne ; Nahass, Ronald ; Peng, Cheng Yuan ; Conway, Brian ; Grebely, Jason ; Howe, Anita Y M ; Gendrano, Isaias N. ; Chen, Erluo ; Huang, Hsueh Cheng ; Dutko, Frank J. ; Nickle, David C. ; Nguyen, Bach Yen ; Wahl, Janice ; Barr, Eliav ; Robertson, Michael N. ; Platt, Heather L. / Elbasvir-grazoprevir to treat hepatitis C virus infection in persons receiving opioid agonist therapy a randomized trial. In: Annals of Internal Medicine. 2016 ; Vol. 165, No. 9. pp. 625-634.
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abstract = "Background: Hepatitis C virus (HCV) infection is common in persons who inject drugs (PWID). Objective: To evaluate elbasvir-grazoprevir in treating HCV infection in PWID. Design: Randomized, placebo-controlled, double-blind trial. (ClinicalTrials.gov: NCT02105688) Setting: Australia, Canada, France, Germany, Israel, the Netherlands, New Zealand, Norway, Spain, Taiwan, the United Kingdom, and the United States. Patients: 301 treatment-naive patients with chronic HCV genotype 1, 4, or 6 infection who were at least 80{\%} adherent to visits for opioid agonist therapy (OAT). Intervention: The immediate-treatment group (ITG) received elbasvir-grazoprevir for 12 weeks; the deferred-treatment group (DTG) received placebo for 12 weeks, no treatment for 4 weeks, then open-label elbasvir-grazoprevir for 12 weeks. Measurements: The primary outcome was sustained virologic response at 12 weeks (SVR12), evaluated separately in the ITG and DTG. Other outcomes included SVR24, viral recurrence or reinfection, and adverse events. Results: The SVR12 was 91.5{\%} (95{\%} CI, 86.8{\%} to 95.0{\%}) in the ITG and 89.5{\%} (95{\%} CI, 81.5{\%} to 94.8{\%}) in the active phase of the DTG. Drug use at baseline and during treatment did not affect SVR12 or adherence to HCV therapy. Among 18 patients with posttreatment viral recurrence through 24-week follow-up, 6 had probable reinfection. If the probable reinfections were assumed to be responses, SVR12 was 94.0{\%} (CI, 89.8{\%} to 96.9{\%}) in the ITG. One patient in the ITG (1 of 201) and 1 in the placebophase DTG (1 of 100) discontinued treatment because of an adverse event. Limitation: These findings may not be generalizable to PWID who are not receiving OAT, nor do they apply to persons with genotype 3 infection, a common strain in PWID. Conclusion: Patients with HCV infection who were receiving OAT and treated with elbasvir-grazoprevir had high rates of SVR12, regardless of ongoing drug use. These results support the removal of drug use as a barrier to interferon-free HCV treatment for patients receiving OAT.",
author = "Dore, {Gregory J.} and Frederick Altice and Litwin, {Alain H.} and Olav Dalgard and Gane, {Edward J.} and Oren Shibolet and Anne Luetkemeyer and Ronald Nahass and Peng, {Cheng Yuan} and Brian Conway and Jason Grebely and Howe, {Anita Y M} and Gendrano, {Isaias N.} and Erluo Chen and Huang, {Hsueh Cheng} and Dutko, {Frank J.} and Nickle, {David C.} and Nguyen, {Bach Yen} and Janice Wahl and Eliav Barr and Robertson, {Michael N.} and Platt, {Heather L.}",
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T1 - Elbasvir-grazoprevir to treat hepatitis C virus infection in persons receiving opioid agonist therapy a randomized trial

AU - Dore, Gregory J.

AU - Altice, Frederick

AU - Litwin, Alain H.

AU - Dalgard, Olav

AU - Gane, Edward J.

AU - Shibolet, Oren

AU - Luetkemeyer, Anne

AU - Nahass, Ronald

AU - Peng, Cheng Yuan

AU - Conway, Brian

AU - Grebely, Jason

AU - Howe, Anita Y M

AU - Gendrano, Isaias N.

AU - Chen, Erluo

AU - Huang, Hsueh Cheng

AU - Dutko, Frank J.

AU - Nickle, David C.

AU - Nguyen, Bach Yen

AU - Wahl, Janice

AU - Barr, Eliav

AU - Robertson, Michael N.

AU - Platt, Heather L.

PY - 2016/11/1

Y1 - 2016/11/1

N2 - Background: Hepatitis C virus (HCV) infection is common in persons who inject drugs (PWID). Objective: To evaluate elbasvir-grazoprevir in treating HCV infection in PWID. Design: Randomized, placebo-controlled, double-blind trial. (ClinicalTrials.gov: NCT02105688) Setting: Australia, Canada, France, Germany, Israel, the Netherlands, New Zealand, Norway, Spain, Taiwan, the United Kingdom, and the United States. Patients: 301 treatment-naive patients with chronic HCV genotype 1, 4, or 6 infection who were at least 80% adherent to visits for opioid agonist therapy (OAT). Intervention: The immediate-treatment group (ITG) received elbasvir-grazoprevir for 12 weeks; the deferred-treatment group (DTG) received placebo for 12 weeks, no treatment for 4 weeks, then open-label elbasvir-grazoprevir for 12 weeks. Measurements: The primary outcome was sustained virologic response at 12 weeks (SVR12), evaluated separately in the ITG and DTG. Other outcomes included SVR24, viral recurrence or reinfection, and adverse events. Results: The SVR12 was 91.5% (95% CI, 86.8% to 95.0%) in the ITG and 89.5% (95% CI, 81.5% to 94.8%) in the active phase of the DTG. Drug use at baseline and during treatment did not affect SVR12 or adherence to HCV therapy. Among 18 patients with posttreatment viral recurrence through 24-week follow-up, 6 had probable reinfection. If the probable reinfections were assumed to be responses, SVR12 was 94.0% (CI, 89.8% to 96.9%) in the ITG. One patient in the ITG (1 of 201) and 1 in the placebophase DTG (1 of 100) discontinued treatment because of an adverse event. Limitation: These findings may not be generalizable to PWID who are not receiving OAT, nor do they apply to persons with genotype 3 infection, a common strain in PWID. Conclusion: Patients with HCV infection who were receiving OAT and treated with elbasvir-grazoprevir had high rates of SVR12, regardless of ongoing drug use. These results support the removal of drug use as a barrier to interferon-free HCV treatment for patients receiving OAT.

AB - Background: Hepatitis C virus (HCV) infection is common in persons who inject drugs (PWID). Objective: To evaluate elbasvir-grazoprevir in treating HCV infection in PWID. Design: Randomized, placebo-controlled, double-blind trial. (ClinicalTrials.gov: NCT02105688) Setting: Australia, Canada, France, Germany, Israel, the Netherlands, New Zealand, Norway, Spain, Taiwan, the United Kingdom, and the United States. Patients: 301 treatment-naive patients with chronic HCV genotype 1, 4, or 6 infection who were at least 80% adherent to visits for opioid agonist therapy (OAT). Intervention: The immediate-treatment group (ITG) received elbasvir-grazoprevir for 12 weeks; the deferred-treatment group (DTG) received placebo for 12 weeks, no treatment for 4 weeks, then open-label elbasvir-grazoprevir for 12 weeks. Measurements: The primary outcome was sustained virologic response at 12 weeks (SVR12), evaluated separately in the ITG and DTG. Other outcomes included SVR24, viral recurrence or reinfection, and adverse events. Results: The SVR12 was 91.5% (95% CI, 86.8% to 95.0%) in the ITG and 89.5% (95% CI, 81.5% to 94.8%) in the active phase of the DTG. Drug use at baseline and during treatment did not affect SVR12 or adherence to HCV therapy. Among 18 patients with posttreatment viral recurrence through 24-week follow-up, 6 had probable reinfection. If the probable reinfections were assumed to be responses, SVR12 was 94.0% (CI, 89.8% to 96.9%) in the ITG. One patient in the ITG (1 of 201) and 1 in the placebophase DTG (1 of 100) discontinued treatment because of an adverse event. Limitation: These findings may not be generalizable to PWID who are not receiving OAT, nor do they apply to persons with genotype 3 infection, a common strain in PWID. Conclusion: Patients with HCV infection who were receiving OAT and treated with elbasvir-grazoprevir had high rates of SVR12, regardless of ongoing drug use. These results support the removal of drug use as a barrier to interferon-free HCV treatment for patients receiving OAT.

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