Efficacy of Glecaprevir and Pibrentasvir in Patients With Genotype 1 Hepatitis C Virus Infection With Treatment Failure After NS5A Inhibitor Plus Sofosbuvir Therapy

Lok, Anna S.; Sulkowski, Mark S.; Kort, Jens; Willner, Ira; Reddy, K. Rajender; Shiffman, Mitchell L.; Hassan, Mohamed A.; Pearlman, Brian L.; Hinestrosa, Federico; Jacobson, Ira M.; Morelli, Giuseppe; Peter, Joy; Vainorius, Monika; Michael, Larry C.; Fried, Michael; Wang, Gary P.; Lü, Wenjing; Larsen, Lois; Nelson, David R.

doi:10.1053/j.gastro.2019.08.008

Cited by 37 publications

(45 citation statements)

References 19 publications

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“…Higher SVR12 (97% and 94% for those with and without cirrhosis) was found in the 16 week arm compared to those receiving the shorter course (86%-90%). SVR12 was also lower in those with NS5A RAS pretreatment (88% vs 97%), although this difference was not statistically significant (77). Treatment-emergent NS3 and/or NS5A resistance mutations were frequently observed in those not achieving SVR12, including the deletion in NS5A at position 32, which is associated with >1000 fold resistance to all NS5A inhibitors (46).…”

Section: Glecaprevir-pibrentasvirmentioning

confidence: 87%

Consensus recommendations for resistance testing in the management of chronic hepatitis C virus infection: Public Health England HCV Resistance Group

Bradshaw

Mbisa

Geretti

et al. 2019

Journal of Infection

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Section: Glecaprevir-pibrentasvirmentioning

confidence: 87%

Consensus recommendations for resistance testing in the management of chronic hepatitis C virus infection: Public Health England HCV Resistance Group

Bradshaw

Mbisa

Geretti

et al. 2019

Journal of Infection

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“…Overall, 25 studies (21 publications and 4 unpublished clinical trials; ClinicalTrials.gov Nos. NCT02707952 substudy1, 3 NCT02723084, 4 NCT02604017, 5 NCT02640482, 6 NCT02640157, 5 NCT02636595, 6 , 7 NCT02966795, 8 NCT02642432, 9 NCT02738138, 10 NCT02651194, 11 NCT03069365, 12 NCT03089944, 13 NCT02446717, 14 , 15 NCT02692703, 16 NCT03117569, 17 NCT02243293, 6 , 18 , 19 NCT03222583, 20 NCT03235349, 21 NCT03092375, 22 NCT03212521, 23 NCT03219216 24 ) were included in this review. A flow chart of the study selection is presented in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, the authors recommend not testing for RAS before retreatment. 22 In another report, retreatment with 12 weeks of glecaprevir/pibrentasvir was successful in a hemodialysis patient with HCV GT 2a who had previously failed 8 weeks of glecaprevir/pibrentasvir therapy. 38 In terms of glecaprevir and pibrentasvir treatment duration, the present analysis found SVR12 rates in patients with 40 The present review did not include an integrated efficacy analysis of SVR12 rates after 16 weeks of glecaprevir/pibrentasvir treatment, as only 2 clinical trials reported these data.…”

Section: Discussionmentioning

confidence: 98%

“…In the same randomized study, patients administered 12 weeks of glecaprevir/pibrentasvir had lower SVR12 rates (88.9%). 22 In MAGELLAN-1, 89% and 91% of patients administered 12 and 16 weeks of glecaprevir/pibrentasvir treatment achieved SVR12, respectively. 15 Glecaprevir/pibrentasvir treatment is effective for hepatitis C and comorbidities, including HIV and SRI.…”

Section: Discussionmentioning

confidence: 99%

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Efficacy and Safety of Glecaprevir/Pibrentasvir for Chronic Hepatitis C Patients: A Systematic Review and Meta-analysis

Wang

Xiao

et al. 2020

Journal of Clinical and Translational Hepatology

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Background and Aims: Glecaprevir/pibrentasvir is a pangenotypic regimen recently approved for the treatment of chronic hepatitis C virus (HCV) infection. The objective of the present review was to summarize the findings from clinical trials to understand how patient-related factors influence glecaprevir/pibrentasvir efficacy (sustained virologic response rates at 12 weeks' after treatment [referred to as SVR12]) and safety. Methods: Data from 21 phase III clinical trials were analyzed. Results: The integrated efficacy analysis included 4,817 patients. Findings showed 97.5% of all included patients with chronic HCV achieved SVR12 in the intention-to-treat population. SVR12 rate was >95% across subgroups of interest. The integrated safety analysis included 4,015 patients. Findings showed that 64.1% of patients reported an adverse event, and <0.1% of patients reported a serious adverse event related to glecaprevir/pibrentasvir. Conclusions: These results indicate that the 8-or 12-week glecaprevir/pibrentasvir treatment is effective for patients infected with HCV genotypes 1-6 without or with compensated cirrhosis, with good safety profiles, irrespective of treatmentexperience. Glecaprevir/pibrentasvir is a good option for patients with human immunodeficiency virus/HCV coinfection and comorbid HCV and severe renal impairment.

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“…Consequently, we extended therapy to 24 weeks again. Although several studies showed high SVR-rates in retreatment scenarios for the GLE/PIB alone [21,24], we added SOF and weight-based ribavirin, as proposed in current EASL-guidelines with regard to the results of the MAGELLAN-Trial [4,25]. Again, our patient showed good initial response with decrease of transaminases and a viral load < 15 IU/ml.…”

Section: Successful Therapy and Outcomementioning

confidence: 99%

Successful fourth line treatment of a relapse patient with chronic hepatitis C virus infection genotype 3a using sofosbuvir, glecaprevir/pibrentasvir, and ribavirin: a case report

Bernhard

Stickel

2020

Z Gastroenterol

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Background Relapses after therapy with direct-acting antiviral agents (DAA) in chronic hepatitis C virus (HCV) infections are rare due to high efficacy of interferon-free therapy regimens. The presence of resistance-associated substitutions (RAS) in proteins targeted by therapy can lead to lower rates of sustained virological response (SVR) in patients receiving DAA-therapy, and little evidence exists as to how to treat these patients. Case Summary We present a case of a multi-drug-resistant HCV-genotype-3a-infection in a 50-year-old female without confirmed cirrhosis but with advanced fibrosis (liver stiffness 11.6 kPa) and low viral load. Resistance testing revealed a Y93H mutation in the NS5A gene. Therapies using sofosbuvir and daclatasvir (1st), sofosbuvir, velpatasvir and ribavirin (2nd), and subsequently with sofosbuvir, velpatasvir, and voxilaprevir (3st) did not achieve SVR. Compliance was good with rapid negativity of HCV RNA at 4 weeks of treatment on all 3 occasions. No virological breakthrough was recorded with all regimens. As a rescue attempt, the patient received 24 weeks of sofosbuvir, glecaprevir/pibrentasvir, and weight-based ribavirin at 1000 mg. With this approach, she achieved SVR but developed hepatocellular carcinoma. Conclusion The combination of sofosbuvir, glecaprevir/pibrentasvir and ribavirin could be a rescue therapy after previous relapses on DAA-therapy, especially in patients with relapse after therapy with sofosbuvir, velpatasvir, and voxilaprevir.

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Efficacy of Glecaprevir and Pibrentasvir in Patients With Genotype 1 Hepatitis C Virus Infection With Treatment Failure After NS5A Inhibitor Plus Sofosbuvir Therapy

Cited by 37 publications

References 19 publications

Consensus recommendations for resistance testing in the management of chronic hepatitis C virus infection: Public Health England HCV Resistance Group

Consensus recommendations for resistance testing in the management of chronic hepatitis C virus infection: Public Health England HCV Resistance Group

Efficacy and Safety of Glecaprevir/Pibrentasvir for Chronic Hepatitis C Patients: A Systematic Review and Meta-analysis

Successful fourth line treatment of a relapse patient with chronic hepatitis C virus infection genotype 3a using sofosbuvir, glecaprevir/pibrentasvir, and ribavirin: a case report

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