Session Title: Parallel Session:
HEPATITIS B: THERAPEUTIC ADVANCES
Presentation Date: Apr 15, 2010
TELBIVUDINE (LDT) PLUS PEG-INTERFERON (PEGIFN) IN HBEAG-POSITIVE CHRONIC HEPATITIS B - VERY POTENT ANTIVIRAL EFFICACY BUT RISK OF PERIPHERAL NEUROPATHY (PN)
P. Marcellin1, C. Avila2, K. Wursthorn3, W.-L. Chuang4, G.K. Lau5, C.-Y. Peng6, E.J. Gane7, H. Fainboim8, M.P. Manns3, N.V. Naoumov2
1Service d'Hépatologie, INSERM, Hôpital Beaujon, Clichy, France, 2Novartis Pharma AG, Basel, Switzerland, 3Hannover Medical School, Hannover, Germany, 4Kaohsiung Medical University, Kaohsiung, Taiwan R.O.C., 5Clinical Trial Center, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China, 6China Medical University Hospital, Taichung, Taiwan R.O.C., 7Middlemore Hospital, Auckland, New Zealand, 8Hospital de Enfermedades Infecciosas, Buenos Aires, Argentina. *firstname.lastname@example.org
Background and aims: HBeAg seroconversion is a key milestone for HBeAg-positive chronic hepatitis B (CHB) patients allowing for treatment discontinuation. Compared with other treatments, higher rates of HBeAg seroconversion (e-seroconversion) are reported with PegIFN or LDT. We aimed to investigate whether PegIFN+LDT combination could further improve antiviral efficacy and e-seroconversion compared to their monotherapy.
Methods: 159 HBeAg-positive CHB patients were randomized (55 LDT, 54 PegIFN, 50 PegIFN+LDT). 110 patients (49 LDT, 43 PegIFN, 18 PegIFN+LDT) reached treatment week 24 (W24), but the study was terminated early due to PN events with PegIFN+LDT. Key efficacy (HBV DNA, ALT, HBsAg/HBeAg quantitation by Abbott Architect) and safety is reported.
Results: Mean baseline HBV DNA levels (log10copies/mL) were 9.8 (LDT), 9.6 (PegIFN), 10.1 (PegIFN+LDT). At W24, LDT containing regimens achieved significantly greater viral load decline than PegIFN (figure 1).
HBV DNA became undetectable in 35%, 7% and 71% of patients (LDT, PegIFN and PegIFN+LDT, respectively), p< 0.002.
At w24, HBsAg/HBeAg decline from baseline was similar with LDT or PegIFN, but greater with PegIFN+LDT (Figure 2);
HBsAg decline (>0.5log10IU/mL) occurred in 41% LDT, 31% PegIFN and 63% PegIFN+LDT treated patients (p=0.03); ALT normalization: 54% LDT, 32% PegIFN, 12% PegIFN+LDT. For the few LDT and PegIFN patients who achieved W48, 7/19 and 3/12 respectively had e-seroconversion.
ITT discontinuations due to SAE/AE occurred in 7.3%, (LDT), 5.6% (PegIFN) and 18%, (PegIFN+LDT). PN cases with PegIFN+LDT were more severe and shorter median time (months) to symptom (4.5, range 2-6) vs LDT (14, range 4-25). 9 SAE PN cases were drug related, 8 were on PegIFN+LDT, 1 was on LDT and at last follow up, 6 were improving, 2 ongoing and 1 unknown.
Conclusions: The combination of PegIFN+LDT provided very potent antiviral efficacy with rapid and profound reduction in HBV DNA and HBsAg/HBeAg levels, but combination therapy with PegIFN+LDT carried an increased risk of PN. The underlying mechanism needs further investigation. Despite increased efficacy, concomitant use of PegIFN+LDT should be avoided at present.