Efficacy of telbivudine with conditional tenofovir intensification in patients with chronic hepatitis B: results from the 2-year roadmap strategy

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Authors
Teerha Piratvisuth, Piyawat Komolmit, Henry LY Chan, Tawesak Tanwandee, Wattana Sukeepaisarnjaroen, Mário G Pessoa, Eduardo Fassio, Suzane K Ono, Fernando Bessone, Jorge Daruich, Stefan Zeuzem, Michael Manns, Alkaz Uddin, Yuhong Dong, Aldo Trylesinski

Article Type
Case Report

DOI
10.7573/dic.212294

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Abstract

Background: A 2-year roadmap study was conducted to evaluate the efficacy and safety of tenofovir intensification at Week 24 in patients with chronic hepatitis B (CHB) receiving telbivudine.

Scope: A prospective multicenter study was conducted in treatment-naive patients with hepatitis B e antigen (HBeAg)- positive CHB. All patients received telbivudine (600 mg/day) until Week 24. Thereafter, patients with detectable hepatitis B virus (HBV) DNA (≥300 copies/mL) were administered tenofovir (300 mg/day) plus telbivudine, and patients with undetectable HBV DNA continued telbivudine monotherapy until Week 104. The primary endpoint was the proportion of patients with undetectable HBV DNA (<300 copies/mL) at Weeks 52 and 104.

Findings: A total of 105 patients were enrolled in the trial, of which 100 were eligible for efficacy analysis. Undetectable HBV DNA levels were observed at Week 24 in 55 patients who continued on with telbivudine monotherapy. The remaining 45 patients with detectable HBV DNA received tenofovir add-on therapy. With monotherapy, 100% (55/55) and 94.5% (52/55) of patients achieved HBV DNA <300 copies/mL at Weeks 52 and 104, respectively; the corresponding values for patients with add-on therapy were 84.4% (38/45) and 93.3% (42/45). Overall, undetectable HBV DNA (<300 copies/mL) was found in 93% (93/100) and 94% (94/100) of patients at Weeks 52 and 104, respectively. HBeAg seroconversion rate was 44.4% (44/99) at Week 104 for the overall patient population. One patient in the monotherapy group and six in the intensification group demonstrated HBsAg clearance at Week 104. HBsAg seroconversion was observed in four patients at Week 104, all belonged to the tenofovir intensification group. Eight patients sustained HBsAg loss during a posttreatment follow-up period of 16 weeks. Alanine aminotransferase (ALT) normalization was constant in the telbivudine monotherapy group, whereas a progressive improvement was observed in the tenofovir intensification group. Two patients in the monotherapy and none in the intensification group experienced viral breakthrough by Week 104. There were no reports of myopathy in either group. The mean changes in estimated glomerular filtration rate (eGFR), estimated using the Modification of Diet in Renal Disease (MDRD) formula, from baseline to Week 104 were +6.145 mL/min/1.73 m2 (p=0.0230) and +7.954 mL/min/1.73 m2 (p=0.0154) in the telbivudine monotherapy and tenofovir intensification groups, respectively. The incidence of serious AEs was four in the telbivudine monotherapy and two in the tenofovir intensification group. The main limitation of this study was limited sample size, which made the power of the observation low, and the absence of a comparative subgroup to assess the progression of patients with detectable HBV DNA without treatment intensification.

Conclusions: Data from this 2-year roadmap study confirmed that telbivudine with add-on tenofovir was effective and well tolerated in patients with CHB. Telbivudine was associated with an improvement in eGFR from baseline in both the groups.

Keywords: chronic hepatitis B, glomerular filtration rate, hepatitis B e antigen, intensification, roadmap, telbivudine, tenofovir, virologic breakthrough

Abbreviations: ALT, alanine aminotransferase; CHB, chronic hepatitis B; CI, confidence interval; eGFR, estimated glomerular filtration rate; HBeAg, hepatitis B e antigen; HBV, hepatitis B virus; IIT, intention to treat; LOCF, last observation carried forward; MDRD, Modification of Diet in Renal Disease; mITT, modified intention to treat; NA, nucleoside analogue; OD, once daily; SD, standard deviation.

Citation: Piratvisuth T, Komolmit P, Chan HLY, Tanwandee T, Sukeepaisarnjaroen W, Pessoa MG, Fassio E, Ono SK, Bessone F, Daruich J, Zeuzem S, Manns M, Uddin A, Dong Y, Trylesinski A. Efficacy of telbivudine with conditional tenofovir intensification in patients with chronic hepatitis B: results from the 2-year roadmap strategy. Drugs in Context 2016; 5: 212294. DOI: 10.7573/dic.212294

Contributions: Piratvisuth T, Komolmit P, Chan HYL, Tanwandee T, Sukeepaisarnjaroen W, Pessoa MG, Fassio E, Ono SK, Bessone F, Daruich J, Zeuzem S, Manns M, Uddin A, Dong Y, and Trylesinski A contributed equally to this work. Piratvisuth T, Dong Y, and Trylesinski A conceived and designed the experiments. Piratvisuth T, Komolmit P, Chan HYL, Tanwandee T, Sukeepaisarnjaroen W, Pessoa MG, Fassio E, Ono SK, Bessone F, Daruich J, Zeuzem S, and Manns M performed the experiments. Piratvisuth T, Uddin A, Dong Y, and Trylesinski A analyzed the data. Piratvisuth T, Komolmit P, Chan HYL, Tanwandee T, Sukeepaisarnjaroen W, Pessoa MG, Fassio E, Ono SK, Bessone F, Daruich J, Zeuzem S, Manns M, Uddin A, Dong Y, and Trylesinski A critically reviewed the manuscript and made amendments.

Acknowledgments: The authors thank Pravin Bolshete, Bhaskara BP, and Rajeeb Ghosh (Novartis Healthcare Pvt. Ltd) for their medical writing assistance and subsequent revisions of the manuscript based on the authors’ review comments and feedback.

Potential conflict of interest: Piratvisuth T, Chan HYL, Pessoa MG, and Bessone F have received research grants from Novartis. Pessoa MG participated as speaker and/or adviser for AbbVie, BMS, Gilead, Janssen, MSD, and Roche; he was an investigator for AbbVie and Roche. Manns M has received research grants from Roche, Gilead, Novartis, Boehringer Ingelheim, Bristol Myers Squibb, Merck, and Janssen and compensation for consultancy and/or lecture activities from Roche, Bristol Myers Squibb, Gilead, Boehringer Ingelheim, Novartis, Merck, Janssen, Idenix, and GlaxoSmithKline. Zeuzem S is a consultant for Abbie, BMS, Gilead, Janssen, and Novartis. Ono S has participated in Novartis clinical trials as an investigator. Fassio E, Tanwandee T, Sukeepaisarnjaroen W, Daruich J, and Komolmit P have nothing to declare. Uddin A, Dong Y, and Trylesinski A are employees of Novartis. The International Committee of Medical Journal Editors’ (ICMJE) Potential Conflicts of Interests forms for the authors are available for download at: https://www.drugsincontext.com/wp-content/uploads/2016/04/dic.212294-COI.pdf.

Funding declaration: This study was supported by Novartis Pharma AG, Basel, Switzerland.

Trial registration number: NCT00651209

Copyright: Copyright © 2016 Piratvisuth T, Komolmit P, Chan HLY, Tanwandee T, Sukeepaisarnjaroen W, Pessoa MG, Fassio E, Ono SK, Bessone F, Daruich J, Zeuzem S, Manns M, Uddin A, Dong Y, Trylesinski A. Distributed under the terms of the Creative Commons License Deed CC BY NC ND 3.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Correct attribution: Copyright © 2016 Piratvisuth T, Komolmit P, Chan HLY, Tanwandee T, Sukeepaisarnjaroen W, Pessoa MG, Fassio E, Ono SK, Bessone F, Daruich J, Zeuzem S, Manns M, Uddin A, Dong Y, Trylesinski A. http://dx.doi.org/10.7573/dic.212294. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 3.0.

Article URL: https://drugsincontext.com/efficacy-of-telbivudine-with-conditional-tenofovir-intensification-in-patients-with-chronic-hepatitis- B-results-from-the-2-year-roadmap-strategy

Correspondence: Dr. Teerha Piratvisuth, MD; NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand. teerha.p@psu.ac.th

Provenance: Submitted; externally peer reviewed

Submitted: 27 January 2016; Peer review comments to author: 7 March 2016; Publication: 22 April 2016

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