Pooled Resistance Analysis in Patients with Hepatitis C Virus Genotype 1 to 6 Infection Treated with Glecaprevir-Pibrentasvir in Phase 2 and 3 Clinical Trials

Krishnan, Preethi; Pilot‐Matias, Tami; Schnell, Gretja; Tripathi, Rakesh; Ng, Teresa I.; Reisch, Thomas; Beyer, Jill; Dekhtyar, Tatyana; Irvin, Michelle; Xie, Wenhui; Larsen, Lois; Mensa, Federico; Collins, Christine A.

doi:10.1128/aac.01249-18

Cited by 67 publications

(98 citation statements)

References 44 publications

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“…Although the pooled sample size and failure rates are small, the presence of these two RAS significantly reduced the OR of achieving SVR‐12 in patients with GT‐3. The baseline A156 mutation in the NS3 region confers the most in‐vitro resistance to Glecaprevir . It was not present at baseline in any of the patients.…”

Section: Discussionmentioning

confidence: 88%

“…The inclusion of only included Japanese patients limits its comparability to the present review. A similar study evaluating pooled global resistance from phase 2 and 3 studies, found no impact of the baseline RAS on SVR12 in patients with CHC treated with G/P regimen, except in treatment‐experienced GT3‐infected patients treated for 12 weeks . The authors attributed the virologic failure, which occurred in 22 patients, to treatment‐emergent substitutions that were detected in NS3 in 50% of patients and NS5A in 82% of patients.…”

Section: Discussionmentioning

confidence: 96%

“…The presence of baseline NS5a mutations also reduced the odds of achieving SVR12. Previously A30K and Y93H were among the most common baseline RAS present . Y93H confers medium to high resistance to DAAs.…”

Section: Discussionmentioning

confidence: 99%

“…Some of these mutations can occur even before the initiation of therapy called baseline RAS, which can negatively impact the treatment response . Recent pooled analyses by Krishnan et al evaluated the impact of RAS on treatment outcomes in patients receiving glecaprevir and pibrentasvir (G/P) . They included all patients enrolled in phase 2 and phase 3 clinical trials of G/P.…”

Section: Introductionmentioning

confidence: 99%

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Systematic review with meta‐analysis: impact of baseline resistance‐associated substitutions on the efficacy of glecaprevir/pibrentasvir among chronic hepatitis C patients

Singh

Maitra

Singh

et al. 2020

Aliment Pharmacol Ther

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Background:The effect of baseline resistance-associated substitutions (RAS) on the sustained virologic response at 12 weeks (SVR12) among chronic hepatitis C (CHC) patients receiving the second generation, pan-genotypic glecaprevir/pibrentasvir (G/P) regimen is unclear. Aim:To assess the effect of RAS on the SVR12 in CHC patients treated with G/P regimen. Methods: The EMBASE, MEDLINE and Cochrane central register of controlled trials databases were searched for relevant studies published before 1 March 2019.The principal outcome was to compare the SVR12 in CHC patients with and without baseline RAS, particularly in genotype-1, genotype-3 and direct-acting anti-virals (DAAs) failure patients. The outcomes were pooled using a random-effects model and odds ratio (OR) was calculated. The risk of bias was assessed using the Cochrane risk of bias tools for randomised and nonrandomised interventional studies. Results: After initially identifying 410 studies, 3302 patients from 17 studies were included. Among 50 cases of virologic failures, 48% had genotype-3 infection, 44% genotype-1 infection and 36% DAA-failure patients. Baseline RAS were present in 44(88%) patients. The most common NS5a and NS3 mutations were Y93H and A166S respectively. The odds of SVR12 were significantly reduced in patients with any baseline RAS (NS3 and/or NS5a) (OR 0.32, 95%C I[0.15, 0.65], I 2 = 0%) and NS5a substitutions (OR 0.36, 95%CI [0.18,0.73]). The impact of RAS on SVR12 was significant among genotype-3 patients, but not among genotype-1 or DAA-failure cases. The presence of Y93H and A30K mutations significantly impacted SVR12 rates in genotype-3 patients. Conclusion: Baseline NS3 or NS5a RAS, especially the NS5a substitutions-A30K, Y93H, decrease the odds of achieving SVR12 in genotype-3 CHC patients. | 491 SINGH et al.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Systematic review with meta‐analysis: impact of baseline resistance‐associated substitutions on the efficacy of glecaprevir/pibrentasvir among chronic hepatitis C patients

Singh

Maitra

Singh

et al. 2020

Aliment Pharmacol Ther

View full text Add to dashboard Cite

show abstract

“…In a pooled efficacy analysis of phase 2 and 3 clinical studies, among 2256 patients, the intent‐to‐treat (ITT) SVR 12 rate was 98% (range 90%‐100%). Less than 1% of patients experienced virological failure . G/P is approved for treatment of adult patients with chronic HCV genotype 1‐6 infection without or with compensated cirrhosis as well as patients with genotype 1 infection who have previously been treated with a regimen containing a HCV nonstructural 5A inhibitor or an NS3/4A protease inhibitor .…”

Section: Introductionmentioning

confidence: 99%

Real‐world effectiveness of 8‐week glecaprevir/pibrentasvir (G/P) for treatment naive, noncirrhotic patients with HCV infection in the TRIO network

et al. 2020

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Summary Background and Aims Glecaprevir/Pibrentasvir (G/P) is the only regimen approved by the United States Food and Drug Administriation with 8‐week treatment duration for chronic HCV genotype (GT) 1‐6 infection in treatment naïve (TN), noncirrhotic (NC) patients. Real world effectiveness data from the US are lacking in these populations and the aim of this study was to address this gap. Methods Data from 560 treatment naïve, noncirrhotic patients who initiated 8 weeks of G/P treatment between August 2017 and April 2018 were collected electronically from providers and specialty pharmacies of the Trio Health network. The primary outcome assessed was Per Protocol (PP) sustained virologic response at 12 weeks post‐treatment (SVR12). Results Seventy one percent (397/560) of patients had HCV genotype 1 infection, and 89% (496/560) had a fibrosis score of F0‐2. The majority of patients (85%) received care in community practices. The per protocol (PP) SVR12 rate was 99% (537/540) and intent‐to‐treat (ITT) SVR12 rate was 96% (537/560). Reasons for not achieving SVR12 were virological failure (0.5%, 3/560), lost‐to‐follow‐up (2%, 13/560) and discontinuation (1%, 7/560). Bivariate analyses including gender, practice type, HCV genotype, eGFR, FIB‐4, baseline HCV viral load and insurance type did not reveal significant association with SVR12. Reasons for discontinuations were medical care unrelated to treatment, patient choice, physician choice, insurance denial, positive drug/alcohol screening and side effects. Conclusion 8‐week G/P treatment is highly effective in 560 treatment naïve, noncirrhotic patients from the TRIO network with SVR12 rates similar to those as in registration trials.

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Sofosbuvir, Glecaprevir, Pibrentasvir, and Ribavirin as a Rescue Therapy in Difficult‐to‐Treat HCV Patients

et al. 2021

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Pooled Resistance Analysis in Patients with Hepatitis C Virus Genotype 1 to 6 Infection Treated with Glecaprevir-Pibrentasvir in Phase 2 and 3 Clinical Trials

Cited by 67 publications

References 44 publications

Systematic review with meta‐analysis: impact of baseline resistance‐associated substitutions on the efficacy of glecaprevir/pibrentasvir among chronic hepatitis C patients

Systematic review with meta‐analysis: impact of baseline resistance‐associated substitutions on the efficacy of glecaprevir/pibrentasvir among chronic hepatitis C patients

Real‐world effectiveness of 8‐week glecaprevir/pibrentasvir (G/P) for treatment naive, noncirrhotic patients with HCV infection in the TRIO network

Sofosbuvir, Glecaprevir, Pibrentasvir, and Ribavirin as a Rescue Therapy in Difficult‐to‐Treat HCV Patients

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