Randomized Trial of Tenofovir With or Without Peginterferon Alfa Followed by Protocolized Treatment Withdrawal in Adults With Chronic Hepatitis B

Author:

Terrault Norah A.1,Lok Anna S.2,Wahed Abdus S.3,Ghany Marc G.4,Perrillo Robert P.5,Fried Michael W.6,Wong David K.7,Khalili Mandana8,Lau Daryl T.Y.9,Sterling Richard K.10,Di Bisceglie Adrian M.11,Lisker-Melman Mauricio12,Cooper Stewart L.13,Chung Ray T.14,Patel Keyur7,Roberts Lewis R.15,Belle Steven H.3,Janssen Harry L.A.7,

Affiliation:

1. Gastrointestinal and Liver Diseases Division, Keck Medicine of University of Southern California, Los Angeles, California, USA;

2. Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA;

3. Departments of Biostatistics, and Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA;

4. Liver Diseases Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA;

5. Baylor University Medical Center, Dallas, Texas, USA;

6. Division of Gastroenterology, University of North Carolina, Chapel Hill, North Carolina, USA;

7. Toronto Centre for Liver Disease, University of Toronto, Toronto, Ontario, Canada;

8. Department of Medicine, University of California San Francisco, San Francisco, California, USA;

9. Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, Massachusetts, USA;

10. Section of Hepatology, Virginia Commonwealth University, Richmond, Virginia, USA;

11. Department of Medicine, University of St. Louis, St. Louis, Missouri, USA;

12. Washington University School of Medicine and John Cochran VA Medical Center, St. Louis, Missouri, USA;

13. San Francisco Center for Liver Disease, California Pacific Medical & Research Institute, San Francisco, California, USA;

14. Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA;

15. Department of Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.

Abstract

INTRODUCTION: Hepatitis B surface antigen (HBsAg) loss is associated with improved long-term outcomes of patients with chronic hepatitis B but is infrequently achieved with current monotherapies. We assessed whether combination strategies that included treatment withdrawal enhanced HBsAg loss. METHODS: A randomized (1:1) trial of tenofovir disoproxil fumarate (TDF) for 192 weeks with or without peginterferon (PegIFN) alfa-2a for the first 24 weeks, followed by withdrawal of TDF at week 192 with 48 weeks of off-treatment follow-up to week 240. The primary end point was HBsAg loss at week 240. RESULTS: Of 201 participants (52% HBeAg positive, 12%/6% genotype A/A2, 7% cirrhosis) randomized to TDF + PegIFN (n = 102) or TDF alone (n = 99), 6 participants had lost HBsAg at the end of the treatment phase (week 192), 5 (5.3%) in the combination group, and 1 (1.0%) in the TDF alone group (P = 0.09). By week 240, 9 participants had cleared HBsAg, 5.3% in combination, and 4.1% in monotherapy arms (P = 0.73). HBsAg decline and loss occurred earlier with TDF + PegIFN than TDF, with a ≥1-logIU/mL qHBsAg decline by week 24 in 28% in TDF + PegIFN compared with 6% in TDF (P = 0.04). HBsAg loss occurred in 7 of 12 (58%) with hepatitis B virus subgenotype A2 (all HBeAg positive) compared with only 2 of 189 (1%) with other hepatitis B virus genotypes and in 8 of 93 (8.6%) HBeAg positive vs 1 of 87 (1.1%) HBeAg negative. DISCUSSION: PegIFN combined TDF followed by protocolized TDF withdrawal led to earlier but not higher percentages of HBsAg clearance. Pretreatment HBeAg positivity and subgenotype A2 were strongly associated with HBsAg clearance.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Gastroenterology,Hepatology

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