Fabien Zoulim1, Jolanta Białkowska-Warzecha2, Mircea Mihai Diculescu3, Adrian Eugen Goldis4, Renate Heyne5, Tomasz Mach6, Patrick Marcellin7,8, Jörg Petersen9, Krzysztof Simon10, Soumaya Bendahmane11, Isabelle Klauck12, Wojciech Wasiak13, Harry L A Janssen14,15. 1. Hepatology Department, Hospices Civils de Lyon, INSERM U1052, INSERM, Lyon University, 151 Cours Albert Thomas, 69424, Lyon Cedex 03, France. fabien.zoulim@inserm.fr. 2. Department of Infectious and Liver Diseases, Medical University of Lodz, Lodz, Poland. 3. Centre of Gastroenterology and Hepatology, Fundeni Clinical Institute, Bucharest, Romania. 4. Clinic of Gastroenterology, University of Medicine, Timisoara, Romania. 5. Leberzentrum Checkpoint, Berlin, Germany. 6. Department of Gastroenterology and Hepatology, Jagiellonian University, Krakow, Poland. 7. Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, University of Paris 7, Paris, France. 8. INSERM Unité 773, Centre de Recherches Claude Bernard sur les Hépatites Virales, Clichy, France. 9. IFI Institute for Interdisciplinary Medicine, Asklepios Klinik St Georg, Hamburg, Germany. 10. Division of Infectious Diseases and Hepatology, Wrocław Medical University, Wrocław, Poland. 11. Bristol-Myers Squibb, Braine-I'Alleud, Belgium. 12. Bristol-Myers Squibb, Paris, France. 13. inVentiv Health Clinical Poland, Warsaw, Poland. 14. Department of Gastroenterology and Hepatology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands. 15. Liver Clinic, Toronto Western and General Hospital, University Health Network, Toronto, Canada.
Abstract
BACKGROUND AND AIMS: In patients with chronic hepatitis B (CHB) who have failed on other nucleos(t)ide analogs (NUCs), the combination of entecavir (ETV) plus tenofovir disoproxil fumarate (TDF), two potent agents with non-overlapping resistance profiles, may provide a single rescue regimen. METHODS: In this single-arm, open-label study, 92 CHB patients with a primary non-response, partial response, or virologic breakthrough on their current NUC were switched to ETV (1 mg) plus TDF (300 mg) and treated for 96 weeks. RESULTS: At baseline, 62 % of patients were HBeAg(+) and mean HBV DNA was 4.4 log10IU/mL. Patients had received ≥1 line of prior NUC therapy, with the latest regimen consisting of monotherapy with ETV (53 %), lamivudine (LVD 22 %), TDF (12 %), adefovir (ADV 4 %), or telbivudine (2 %), or combinations of these agents (7 %); 58 % had evidence of single- or multidrug resistance mutations (LVD 52 %, ETV 26 %; ADV 7 %). Response rates for HBV DNA <50 IU/mL were 76 % (70/92) at week 48 (primary endpoint), and 85 % (78/92) at week 96, including 80 % (16/20) in prior LVD failures, 100 % (4/4) in ADV failures, 82 % (9/11) in TDF failures, and 88 % (42/48) in ETV failures. No treatment-emergent resistance to ETV or ADV was observed. ETV/TDF was well tolerated, with no significant renal or additive toxicities observed. CONCLUSIONS: In NUC-experienced patients who have failed prior NUC therapy, ETV/TDF was well tolerated and effective, achieving virologic suppression through 96 weeks in the majority (85 %), irrespective of prior NUC exposure, without occurrence of treatment-emergent resistance to either agent.
BACKGROUND AND AIMS: In patients with chronic hepatitis B (CHB) who have failed on other nucleos(t)ide analogs (NUCs), the combination of entecavir (ETV) plus tenofovir disoproxil fumarate (TDF), two potent agents with non-overlapping resistance profiles, may provide a single rescue regimen. METHODS: In this single-arm, open-label study, 92 CHB patients with a primary non-response, partial response, or virologic breakthrough on their current NUC were switched to ETV (1 mg) plus TDF (300 mg) and treated for 96 weeks. RESULTS: At baseline, 62 % of patients were HBeAg(+) and mean HBV DNA was 4.4 log10IU/mL. Patients had received ≥1 line of prior NUC therapy, with the latest regimen consisting of monotherapy with ETV (53 %), lamivudine (LVD 22 %), TDF (12 %), adefovir (ADV 4 %), or telbivudine (2 %), or combinations of these agents (7 %); 58 % had evidence of single- or multidrug resistance mutations (LVD 52 %, ETV 26 %; ADV 7 %). Response rates for HBV DNA <50 IU/mL were 76 % (70/92) at week 48 (primary endpoint), and 85 % (78/92) at week 96, including 80 % (16/20) in prior LVD failures, 100 % (4/4) in ADV failures, 82 % (9/11) in TDF failures, and 88 % (42/48) in ETV failures. No treatment-emergent resistance to ETV or ADV was observed. ETV/TDF was well tolerated, with no significant renal or additive toxicities observed. CONCLUSIONS: In NUC-experienced patients who have failed prior NUC therapy, ETV/TDF was well tolerated and effective, achieving virologic suppression through 96 weeks in the majority (85 %), irrespective of prior NUC exposure, without occurrence of treatment-emergent resistance to either agent.
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