Real‐world effectiveness and safety of glecaprevir/pibrentasvir for the treatment of chronic hepatitis C infection: data from the German Hepatitis C‐Registry

Abstract

Background: Glecaprevir/pibrentasvir is a pangenotypic direct-acting antiviral regimen approved for treating adults chronically infected with hepatitis C virus (HCV).There are limited real-world data on glecaprevir/pibrentasvir to date.Aim: To evaluate the effectiveness and safety of glecaprevir/pibrentasvir under realworld conditions in the German Hepatitis C-Registry (DHC-R). Methods:The DHC-R is an ongoing, non-interventional, multicentre, prospective, observational cohort study that monitors patients with chronic HCV infection. Data were collected from patients who initiated glecaprevir/pibrentasvir and completed a screening visit on or after 2 August 2017. The primary effectiveness endpoint was sustained virological response at post-treatment Week 12 (SVR12). Safety and tolerability were also assessed. Results:As of 15 July 2018, 586 patients received glecaprevir/pibrentasvir and had documented SVR12 data, treatment discontinuation, loss to follow-up or HCV reinfection. Five hundred and fifty-two patients (94%) received on-label treatment. At baseline, most on-label patients were infected with HCV genotype 1 (53%) or 3 (33%), HCV treatment-naïve (90%), without cirrhosis (94%), and treated for 8 weeks (93%). Five hundred and thirty-four patients (96.7%) achieved SVR12 (intention-totreat [ITT] analysis). By modified ITT analysis (excluding patients who discontinued and did not achieve SVR12 or patients lost to follow-up), the SVR12 rate was 99.4% (n/N = 534/537). There was one documented virological failure (relapse) and two documented HCV reinfections. One hundred and forty-two (26%) adverse events (AEs) and 9 (2%) serious AEs occurred; 2 (<1%) AEs led to treatment discontinuation. All patients treated off-label (N = 34) achieved SVR12.Conclusion: Glecaprevir/pibrentasvir was highly effective and well tolerated under real-world conditions. Clinical trial number: DRKS00009717 (German Clinical Trials Register, DRKS).

Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases–Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection

“…Several well-designed, robust clinical trials have demonstrated the safety (147) and high curative efficacy of glecaprevir/pibrentasvir (148)(149)(150)(151)(152)(153)(154)(155)(156)(157)(158) and sofosbuvir/ velpatasvir (159)(160)(161)(162)(163)(164) among treatment-naive persons without cirrhosis regardless of HCV genotype. These findings have been confirmed in real-world cohort studies for both glecaprevir/pibrentasvir (165)(166)(167) and sofosbuvir/velpatasvir. (167)(168)(169)(170)(171) Based on these data, 8 weeks of glecaprevir/pibrentasvir or 12 weeks of sofosbuvir/velpatasvir is recommended for adults eligible for the simplified treatment algorithm.…”

“…Eight weeks of the daily fixed‐dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg) gained FDA approval for use in treatment‐naive or interferon‐experienced adolescents aged ≥ 12 years or weighing ≥ 45 kg with any HCV genotype infection, without cirrhosis or with compensated cirrhosis (Child‐Pugh A). Although the registration trial included only adolescents with genotype 1‐4, glecaprevir/pibrentasvir garnered FDA approval for all genotypes based on the safety and efficacy of the regimen demonstrated in adults . The recommendations for use of glecaprevir/pibrentasvir in treatment‐experienced adolescents are also based on clinical trial data from adults .…”

“…Although the registration trial included only adolescents with genotype 1-4, (276) glecaprevir/pibrentasvir garnered FDA approval for all genotypes based on the safety and efficacy of the regimen demonstrated in adults. (148)(149)(150)(152)(153)(154)(155)(156)(157)(165)(166)(167)277) The recommendations for use of glecaprevir/pibrentasvir in treatmentexperienced adolescents are also based on clinical trial data from adults. (154,156,176,(278)(279)(280) Given its pangenotypic activity and safety and efficacy records in adults, the HCV guidance panel recommends glecaprevir/pibrentasvir as the first choice for adolescent HCV treatment.…”

Glecaprevir/pibrentasvir for patients with chronic hepatitis C virus infection: Real‐world effectiveness and safety in Taiwan

“…[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][32][33][34] Furthermore, 549 (83.4%) of our patients received 8-week treatment regimen, implying that most patients were easy-to-treat population. [18][19][20][21][22][23][24] Although the SVR 12 rate in cirrhotic patients receiving 12-week treatment regimen (94.2%) were numerically lower that the non-cirrhotic patients receiving 8-week treatment (98.9%) by EP analysis, the PP analysis showed that only 2% of the cirrhotic patients had virologic failure. 35 Among the 6 patients receiving 16-week treatment regimen, includ- The causal relationship between the symptoms and the use of GLE/PIB was unclear.…”

“…[10][11][12][13][14][15][16][17][18][19] Following the clinical trials which demonstrated the excellent safety and efficacy by GLE/PIB, the real-world data from Western countries and Japan revealed that the SVR 12 rates according to label recommendation were also excellent and were comparable to the reports from clinical trials. [20][21][22][23][24][25][26][27] In 2018, GLE/PIB was reimbursed by Taiwan National Health Insurance (NHI) for patients with chronic HCV infection who had a hepatic fibrosis stage of ≥F3. In 2019, Taiwan NHI cancelled reimbursement restriction and approved physicians to treat all HCV viraemic patients by GLE/PIB.…”