JHEP reports : innovation in hepatology · 2026
Outcomes of nucleos(t)ide analogue discontinuation following finite xalnesiran-based therapies in chronic hepatitis B.
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Cheng Cong, Xie Qing, Gane Edward, Morano Amado Luis Enrique, Yang Sheng-Shun, Zhang Wenhong, Jia Jidong, Asselah Tarik, Kao Jia-Horng, Peng Cheng-Yuan, Su Wei-Wen, Tanwandee Tawesak, Liang Xieer, Catanese Maria Teresa, Chen Ethan, Chughlay Farouk, Das Sudip, Glavini Katerina, Guerreiro Nelson, Huang Yan, Kazma Rémi, Liang Yukun, McGeown Claire, Patil Avinash, Upmanyu Ruchi, Wat Cynthia, Yuen Man-Fung, Hou Jinlin, Piranga Study Group
Аннотация
BACKGROUND & AIMS: Novel regimens aimed at achieving functional cure of chronic hepatitis B (CHB) in virologically suppressed participants require the withdrawal of nucleos(t)ide analogue (NA). However, data from clinical trials are limited.
METHODS: Piranga is a phase II platform trial that evaluated four xalnesiran regimens with or without an immunomodulator in virologically suppressed participants with CHB. All participants continued the established NA therapy until NA stopping criteria were met at the end of treatment or during follow-up. Participants who stopped NA were monitored and restarted NA if restarting criteria were met. This post hoc evaluation reports the NA discontinuation events and outcomes.
RESULTS: Among 121 participants, 58 (48%) met NA stopping criteria and 40 (33%) discontinued NA. Of these 40, 17 (43%) met NA restarting criteria, 16 (40%) restarted NA, and 24 (60%) remained off NA by the end of the study. Among participants who remained off NA, five achieved and maintained HBsAg loss (HBsAg <0.05 IU/ml) and HBV DNA undetectable (HBV DNA <10 IU/ml); all were in treatment arms with an immunomodulator. Of the 40 participants who discontinued NA, 19 (48%) experienced virological relapse (VR), three (8%) of whom further developed clinical relapse. The majority of participants restarted NA following VR. VR and clinical relapse events were associated with preserved liver function and resolved without sequelae.
CONCLUSIONS: NA discontinuation after xalnesiran-based therapy was safely managed with the application of prespecified NA stopping and restarting criteria and close monitoring. Five participants achieved and maintained HBsAg loss and undetectable HBV DNA while off NA until the end of the study.
IMPACT AND IMPLICATIONS: Novel regimens aiming to achieve functional cure of CHB in virologically suppressed participants require the withdrawal of NA, yet data from clinical trials are limited. This study addresses a critical question in the treatment of CHB - the optimization of NA discontinuation strategies for novel combination regimens in development aiming to achieve functional cure in participants with chronic hepatitis B. These findings help advance the framework for clinicians and researchers to safely and efficiently manage NA discontinuation, which is central to achieving a functional cure.
CLINICAL TRIALS REGISTRATION: The study is registered at ClinicalTrials.gov (NCT04225715).
METHODS: Piranga is a phase II platform trial that evaluated four xalnesiran regimens with or without an immunomodulator in virologically suppressed participants with CHB. All participants continued the established NA therapy until NA stopping criteria were met at the end of treatment or during follow-up. Participants who stopped NA were monitored and restarted NA if restarting criteria were met. This post hoc evaluation reports the NA discontinuation events and outcomes.
RESULTS: Among 121 participants, 58 (48%) met NA stopping criteria and 40 (33%) discontinued NA. Of these 40, 17 (43%) met NA restarting criteria, 16 (40%) restarted NA, and 24 (60%) remained off NA by the end of the study. Among participants who remained off NA, five achieved and maintained HBsAg loss (HBsAg <0.05 IU/ml) and HBV DNA undetectable (HBV DNA <10 IU/ml); all were in treatment arms with an immunomodulator. Of the 40 participants who discontinued NA, 19 (48%) experienced virological relapse (VR), three (8%) of whom further developed clinical relapse. The majority of participants restarted NA following VR. VR and clinical relapse events were associated with preserved liver function and resolved without sequelae.
CONCLUSIONS: NA discontinuation after xalnesiran-based therapy was safely managed with the application of prespecified NA stopping and restarting criteria and close monitoring. Five participants achieved and maintained HBsAg loss and undetectable HBV DNA while off NA until the end of the study.
IMPACT AND IMPLICATIONS: Novel regimens aiming to achieve functional cure of CHB in virologically suppressed participants require the withdrawal of NA, yet data from clinical trials are limited. This study addresses a critical question in the treatment of CHB - the optimization of NA discontinuation strategies for novel combination regimens in development aiming to achieve functional cure in participants with chronic hepatitis B. These findings help advance the framework for clinicians and researchers to safely and efficiently manage NA discontinuation, which is central to achieving a functional cure.
CLINICAL TRIALS REGISTRATION: The study is registered at ClinicalTrials.gov (NCT04225715).