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Effect of Peg-IFN on the viral kinetics of patients with HDV infection treated with bulevirtide.
El Messaoudi, Selma; Brichler, Ségolène; Fougerou-Leurent, Claire; Gordien, Emmanuel; Gerber, Athenaïs; Kortebi, Amal; Lagadic, Garance; Subic-Levrero, Miroslava; Metivier, Sophie; Pol, Stanislas; Minello, Anne; Ratziu, Vlad; Leroy, Vincent; Mathurin, Philippe; Alric, Laurent; Coulibaly, Fatoumata; Pawlotsky, Jean-Michel; Zoulim, Fabien; de Lédinghen, Victor; Guedj, Jérémie.
Afiliación
  • El Messaoudi S; Université Paris Cité, IAME, Inserm, Paris, France.
  • Brichler S; National Reference Center for Viral Hepatitis B, C, and D, Department of Clinical Microbiology, Hôpital Avicenne AP-HP, Université Sorbonne Paris Nord, Bobigny, INSERM U955, Créteil, France.
  • Fougerou-Leurent C; Clinical Pharmacology Department, CHU Rennes, Rennes, France.
  • Gordien E; CIC 1414 (Clinical Investigation Center), INSERM, Rennes, France.
  • Gerber A; National Reference Center for Viral Hepatitis B, C, and D, Department of Clinical Microbiology, Hôpital Avicenne AP-HP, Université Sorbonne Paris Nord, Bobigny, INSERM U955, Créteil, France.
  • Kortebi A; National Reference Center for Viral Hepatitis B, C, and D, Department of Clinical Microbiology, Hôpital Avicenne AP-HP, Université Sorbonne Paris Nord, Bobigny, INSERM U955, Créteil, France.
  • Lagadic G; Clinical Pharmacology Department, CHU Rennes, Rennes, France.
  • Subic-Levrero M; CIC 1414 (Clinical Investigation Center), INSERM, Rennes, France.
  • Metivier S; Clinical Pharmacology Department, CHU Rennes, Rennes, France.
  • Pol S; CIC 1414 (Clinical Investigation Center), INSERM, Rennes, France.
  • Minello A; Department of Hepatology, Hospices Civils de Lyon, INSERM Unit 1052, Université Claude Bernard Lyon 1, France.
  • Ratziu V; Department of Hepatology, CHU Rangueil, Toulouse, France.
  • Leroy V; Department of Hepatology, Hôpital Cochin, AP-HP, Université Paris-René Descartes, INSERM U1016, Paris, France.
  • Mathurin P; Department of Hepatology and Gastroenterology, University hospital Dijon, INSERM UMR 1231, France.
  • Alric L; Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Hôpital Pitié Salpêtrière, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.
  • Coulibaly F; Department of Hepatology and Gastroenterology, Centre Hospitalo-Universitaire, INSERM U1209, Université Grenoble Alpes, Grenoble, France.
  • Pawlotsky JM; Service des maladies de l'appareil digestif, Université Lille 2 and Inserm U795, Lille, France.
  • Zoulim F; Department of Internal Medicine and Digestive Diseases, UMR-152, Toulouse III University, Toulouse, France.
  • de Lédinghen V; Clinical research department, ANRS Maladies infectieuses émergentes, Paris, France.
  • Guedj J; National Reference Center for Viral Hepatitis B, C, and D, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Inserm U955, Créteil, France.
JHEP Rep ; 6(8): 101070, 2024 Aug.
Article en En | MEDLINE | ID: mdl-39100818
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: JHEP Rep Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: JHEP Rep Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Países Bajos