ÿþ<!DOCTYPE HTML PUBLIC "-//W3C//DTD HTML 4.01 Transitional//EN" "http://www.w3.org/TR/html4/loose.dtd"> <html> <head> <meta http-equiv="Content-Type" content="text/html; charset=iso-8859-1"> <title>EASL 2010 - Oral Presentations</title> <link rel="stylesheet" type="text/css" href="style.css"> </head> <body> <table width="750" align="center" border="0" cellspacing="0" cellpadding="0" class="MainTable"> <tr> <td><img src="http://www2.kenes.com/liver-congress2010/PublishingImages/top_ei.jpg" width="760" height="129" /></td> </tr> <tr> <td class="content"><h1>Oral Presentations</h1> <P><b>Session Title:</b> Parallel Session: HEPATITIS B: THERAPEUTIC ADVANCES<br><b>Presentation Date:</b> Apr 15, 2010</P><h2 align='left'><B>TELBIVUDINE (LDT) PLUS PEG-INTERFERON (PEGIFN) IN HBEAG-POSITIVE CHRONIC HEPATITIS B - VERY POTENT ANTIVIRAL EFFICACY BUT RISK OF PERIPHERAL NEUROPATHY (PN)</B></h2> <p align='left'><b>P. Marcellin</b><sup>1</sup>, C. Avila<sup>2</sup>, K. Wursthorn<sup>3</sup>, W.-L. Chuang<sup>4</sup>, G.K. Lau<sup>5</sup>, C.-Y. Peng<sup>6</sup>, E.J. Gane<sup>7</sup>, H. Fainboim<sup>8</sup>, M.P. Manns<sup>3</sup>, N.V. Naoumov<sup>2</sup><br> <em><sup>1</sup>Service d'Hépatologie, INSERM, Hôpital Beaujon, Clichy, France, <sup>2</sup>Novartis Pharma AG, Basel, Switzerland, <sup>3</sup>Hannover Medical School, Hannover, Germany, <sup>4</sup>Kaohsiung Medical University, Kaohsiung, Taiwan R.O.C., <sup>5</sup>Clinical Trial Center, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China, <sup>6</sup>China Medical University Hospital, Taichung, Taiwan R.O.C., <sup>7</sup>Middlemore Hospital, Auckland, New Zealand, <sup>8</sup>Hospital de Enfermedades Infecciosas, Buenos Aires, Argentina. *patrick.marcellin@bjn.ap-hop-paris.fr</em></p><br> <p align='justify'><b><b>Background and aims: </b></b> 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. <br><b><b>Methods: </b> </b>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. <br><b><b>Results: </b> </b>Mean baseline HBV DNA levels (log<sub>10</sub>copies/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).<br><img hspace=5 vspace=5 src=pictures/p_248_00174.jpg ><br><i>[Figure 1]</i><br> HBV DNA became undetectable in 35%, 7% and 71% of patients (LDT, PegIFN and PegIFN+LDT, respectively), p< 0.002. <br>At w24, HBsAg/HBeAg decline from baseline was similar with LDT or PegIFN, but greater with PegIFN+LDT (Figure 2);<br><img hspace=5 vspace=5 src=pictures/p_248_00150.jpg ><br><i>[Figure 2]</i><br> HBsAg decline (>0.5log<sub>10</sub>IU/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. <br>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. <br><b><b>Conclusions: </b> </b>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. <br></p> <img src='pictures/p_248_00150.jpg'> <img src='pictures/p_248_00174.jpg'> <br><a href="javascript://;" onclick="history.back()">Back</a><br> <p>&nbsp;</p> <p>&nbsp;</p></td> </tr> </table> </body> </html>