52-week efficacy and safety of telbivudine with conditional tenofovir intensification at week 24 in HBeAg-positive chronic hepatitis B

Teerha Piratvisuth, Piyawat Komolmit, Tawesak Tanwandee, Wattana Sukeepaisarnjaroen, Henry L Y Chan, Mário G Pessôa, Eduardo Fassio, Suzane K Ono, Fernando Bessone, Jorge Daruich, Stefan Zeuzem, Hugo Cheinquer, Rashidkhan Pathan, Yuhong Dong, Aldo Trylesinski, Teerha Piratvisuth, Piyawat Komolmit, Tawesak Tanwandee, Wattana Sukeepaisarnjaroen, Henry L Y Chan, Mário G Pessôa, Eduardo Fassio, Suzane K Ono, Fernando Bessone, Jorge Daruich, Stefan Zeuzem, Hugo Cheinquer, Rashidkhan Pathan, Yuhong Dong, Aldo Trylesinski

Abstract

Background and aims: The Roadmap concept is a therapeutic framework in chronic hepatitis B for the intensification of nucleoside analogue monotherapy based on early virologic response. The efficacy and safety of this approach applied to telbivudine treatment has not been investigated.

Methods: A multinational, phase IV, single-arm open-label study (ClinicalTrials.gov ID NCT00651209) was undertaken in HBeAg-positive, nucleoside-naive adult patients with chronic hepatitis B. Patients received telbivudine (600 mg once-daily) for 24 weeks, after which those with undetectable serum HBV DNA (<300 copies/mL) continued to receive telbivudine alone while those with detectable DNA received telbivudine plus tenofovir (300 mg once-daily). Outcomes were assessed at Week 52.

Results: 105 patients commenced telbivudine monotherapy, of whom 100 were included in the efficacy analysis. Fifty-five (55%) had undetectable HBV DNA at Week 24 and continued telbivudine monotherapy; 45 (45%) received tenofovir intensification. At Week 52, the overall proportion of undetectable HBV DNA was 93% (93/100) by last-observation-carried-forward analysis (100% monotherapy group, 84% intensification group) and no virologic breakthroughs had occurred. ALT normalization occurred in 77% (87% monotherapy, 64% intensification), HBeAg clearance in 43% (65% monotherapy, 16% intensification), and HBeAg seroconversion in 39% (62% monotherapy, 11% intensification). Six patients had HBsAg clearance. Myalgia was more common in the monotherapy group (19% versus 7%). No decrease in the mean glomerular filtration rate occurred in either treatment group at Week 52.

Conclusions: Telbivudine therapy with tenofovir intensification at Week 24, where indicated by the Roadmap strategy, appears effective and well tolerated for the treatment of chronic hepatitis B.

Conflict of interest statement

Competing Interests: The authors have read the journal’s policy and have the following conflicts: RP, YD, and AT are all employees of Novartis, the funder of this study. The following employees of Novartis Pharma played key roles in the design, execution and analysis of the study and in the drafting of this manuscript: Efsevia Albanis, Patricia Lopez, Claudio Avila, and George Harb (study design and data analysis); Weibin Bao (data analysis); Michele Gysen, Joe Mostillo, Kevin Poirier (study operations); Mechthild Jung (study operations and manuscript preparation); Charles Koehne (manuscript preparation). Editorial assistance with the drafting of the manuscript in association with the authors was provided by a professional medical writer (Nicholas Fitch) with funding from Novartis Pharma AG. There are no patents, products in development, or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Patient disposition.
Figure 1. Patient disposition.
Figure 2. Study design.
Figure 2. Study design.
Figure 3. Changes from baseline in HBV…
Figure 3. Changes from baseline in HBV DNA by post-Week 24 treatment (efficacy population).
Figure 4. Week 52 glomerular filtration rate…
Figure 4. Week 52 glomerular filtration rate (MDRD) changes, by baseline rate and treatment (efficacy population).

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