Selma El Messaoudi , Ségolène Brichler , Claire Fougerou-Leurent , Emmanuel Gordien , Athenaïs Gerber , Amal Kortebi , Garance Lagadic , Miroslava Subic-Levrero , Sophie Metivier , Stanislas Pol , Anne Minello , Vlad Ratziu , Vincent Leroy , Philippe Mathurin , Laurent Alric , Fatoumata Coulibaly , Jean-Michel Pawlotsky , Fabien Zoulim , Victor de Lédinghen , Jérémie Guedj
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The viral kinetics during bulevirtide therapy and the effect of combining bulevirtide with pegylated-interferon (Peg-IFN) are unknown.</p></div><div><h3>Methods</h3><p>We used mathematical modelling to analyze the viral kinetics in two French observational cohorts of 183 patients receiving bulevirtide with or without Peg-IFN for 48 weeks.</p></div><div><h3>Results</h3><p>The efficacy of bulevirtide in blocking cell infection was estimated to 90.3%, whereas Peg-IFN blocked viral production with an efficacy of 92.4%, albeit with large inter-individual variabilities. The addition of Peg-IFN to bulevirtide was associated with a more rapid virological decline, with a rate of virological response (>2 log of decline or undetectability) at week 48 of 86.9% (95% prediction interval [PI] = [79.7–95.0]), compared with 56.1% (95% PI = [46.4–66.7]) with bulevirtide only. The model was also used to predict the probability to achieve a cure of viral infection, with a rate of 8.8% (95% PI = [3.5–13.2]) with bulevirtide compared with 18.8% (95% PI = [11.6–29.0]) with bulevirtide + Peg-IFN. Mathematical modelling suggests that after 144 weeks of treatment, the rates of viral cure could be 42.1% (95% PI = [33.3–52.6]) with bulevirtide and 66.7% (95% PI = [56.5–76.8]) with bulevirtide + Peg-IFN.</p></div><div><h3>Conclusions</h3><p>In this analysis of real-world data, Peg-IFN strongly enhanced the kinetics of viral decline in patients treated with bulevirtide. Randomized clinical trials are warranted to assess the virological and clinical benefit of this combination, and to identify predictors of poor response to treatment.</p></div><div><h3>Impact and implications</h3><p>Bulevirtide has been approved for chronic HDV infection by regulatory agencies in Europe based on its good safety profile and rapid virological response after treatment initiation, but the optimal duration of treatment and the chance to achieve a sustained virological response remain unknown. The results presented in this study have a high impact for clinicians and investigators as they provide important knowledge on the long-term virological benefits of a combination of Peg-IFN and bulevirtide in patients with CHD. Clinical trials are now warranted to confirm those predictions.</p></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":null,"pages":null},"PeriodicalIF":9.5000,"publicationDate":"2024-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589555924000715/pdfft?md5=36d53876256b04b200881a740561ac7d&pid=1-s2.0-S2589555924000715-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Effect of Peg-IFN on the viral kinetics of patients with HDV infection treated with bulevirtide\",\"authors\":\"Selma El Messaoudi , Ségolène Brichler , Claire Fougerou-Leurent , Emmanuel Gordien , Athenaïs Gerber , Amal Kortebi , Garance Lagadic , Miroslava Subic-Levrero , Sophie Metivier , Stanislas Pol , Anne Minello , Vlad Ratziu , Vincent Leroy , Philippe Mathurin , Laurent Alric , Fatoumata Coulibaly , Jean-Michel Pawlotsky , Fabien Zoulim , Victor de Lédinghen , Jérémie Guedj\",\"doi\":\"10.1016/j.jhepr.2024.101070\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background & Aims</h3><p>Bulevirtide is a first-in-class entry inhibitor antiviral treatment for chronic hepatitis D. The viral kinetics during bulevirtide therapy and the effect of combining bulevirtide with pegylated-interferon (Peg-IFN) are unknown.</p></div><div><h3>Methods</h3><p>We used mathematical modelling to analyze the viral kinetics in two French observational cohorts of 183 patients receiving bulevirtide with or without Peg-IFN for 48 weeks.</p></div><div><h3>Results</h3><p>The efficacy of bulevirtide in blocking cell infection was estimated to 90.3%, whereas Peg-IFN blocked viral production with an efficacy of 92.4%, albeit with large inter-individual variabilities. The addition of Peg-IFN to bulevirtide was associated with a more rapid virological decline, with a rate of virological response (>2 log of decline or undetectability) at week 48 of 86.9% (95% prediction interval [PI] = [79.7–95.0]), compared with 56.1% (95% PI = [46.4–66.7]) with bulevirtide only. The model was also used to predict the probability to achieve a cure of viral infection, with a rate of 8.8% (95% PI = [3.5–13.2]) with bulevirtide compared with 18.8% (95% PI = [11.6–29.0]) with bulevirtide + Peg-IFN. Mathematical modelling suggests that after 144 weeks of treatment, the rates of viral cure could be 42.1% (95% PI = [33.3–52.6]) with bulevirtide and 66.7% (95% PI = [56.5–76.8]) with bulevirtide + Peg-IFN.</p></div><div><h3>Conclusions</h3><p>In this analysis of real-world data, Peg-IFN strongly enhanced the kinetics of viral decline in patients treated with bulevirtide. Randomized clinical trials are warranted to assess the virological and clinical benefit of this combination, and to identify predictors of poor response to treatment.</p></div><div><h3>Impact and implications</h3><p>Bulevirtide has been approved for chronic HDV infection by regulatory agencies in Europe based on its good safety profile and rapid virological response after treatment initiation, but the optimal duration of treatment and the chance to achieve a sustained virological response remain unknown. The results presented in this study have a high impact for clinicians and investigators as they provide important knowledge on the long-term virological benefits of a combination of Peg-IFN and bulevirtide in patients with CHD. 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Effect of Peg-IFN on the viral kinetics of patients with HDV infection treated with bulevirtide
Background & Aims
Bulevirtide is a first-in-class entry inhibitor antiviral treatment for chronic hepatitis D. The viral kinetics during bulevirtide therapy and the effect of combining bulevirtide with pegylated-interferon (Peg-IFN) are unknown.
Methods
We used mathematical modelling to analyze the viral kinetics in two French observational cohorts of 183 patients receiving bulevirtide with or without Peg-IFN for 48 weeks.
Results
The efficacy of bulevirtide in blocking cell infection was estimated to 90.3%, whereas Peg-IFN blocked viral production with an efficacy of 92.4%, albeit with large inter-individual variabilities. The addition of Peg-IFN to bulevirtide was associated with a more rapid virological decline, with a rate of virological response (>2 log of decline or undetectability) at week 48 of 86.9% (95% prediction interval [PI] = [79.7–95.0]), compared with 56.1% (95% PI = [46.4–66.7]) with bulevirtide only. The model was also used to predict the probability to achieve a cure of viral infection, with a rate of 8.8% (95% PI = [3.5–13.2]) with bulevirtide compared with 18.8% (95% PI = [11.6–29.0]) with bulevirtide + Peg-IFN. Mathematical modelling suggests that after 144 weeks of treatment, the rates of viral cure could be 42.1% (95% PI = [33.3–52.6]) with bulevirtide and 66.7% (95% PI = [56.5–76.8]) with bulevirtide + Peg-IFN.
Conclusions
In this analysis of real-world data, Peg-IFN strongly enhanced the kinetics of viral decline in patients treated with bulevirtide. Randomized clinical trials are warranted to assess the virological and clinical benefit of this combination, and to identify predictors of poor response to treatment.
Impact and implications
Bulevirtide has been approved for chronic HDV infection by regulatory agencies in Europe based on its good safety profile and rapid virological response after treatment initiation, but the optimal duration of treatment and the chance to achieve a sustained virological response remain unknown. The results presented in this study have a high impact for clinicians and investigators as they provide important knowledge on the long-term virological benefits of a combination of Peg-IFN and bulevirtide in patients with CHD. Clinical trials are now warranted to confirm those predictions.
期刊介绍：
JHEP Reports is an open access journal that is affiliated with the European Association for the Study of the Liver (EASL). It serves as a companion journal to the highly respected Journal of Hepatology.
The primary objective of JHEP Reports is to publish original papers and reviews that contribute to the advancement of knowledge in the field of liver diseases. The journal covers a wide range of topics, including basic, translational, and clinical research. It also focuses on global issues in hepatology, with particular emphasis on areas such as clinical trials, novel diagnostics, precision medicine and therapeutics, cancer research, cellular and molecular studies, artificial intelligence, microbiome research, epidemiology, and cutting-edge technologies.
In summary, JHEP Reports is dedicated to promoting scientific discoveries and innovations in liver diseases through the publication of high-quality research papers and reviews covering various aspects of hepatology.
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