Long-term safety and tolerability of entecavir in patients with chronic hepatitis B in the rollover study ETV-901

PubMed ID: 22233350Objective: To review long-term safety data from the rollover study ETV-901, focusing on adverse events (AEs) with a potential nucleos(t)ide association. Methods: The open-label study ETV-901 (AI463901) assessed the safety of entecavir in chronic hepatitis B patients who received entecavir, lamivudine or adefovir monotherapy in previous entecavir Phase II/III studies. Long-term cumulative safety results are based on reported AEs, regardless of causal relationship. Results: Median exposure to entecavir in study ETV-901 was 184 weeks. Commonly reported AEs (? 10%) were upper respiratory tract infection, headache and nasopharyngitis. Most AEs were mild to moderate; 203 (19%) patients reported grade 3 4 AEs, with 45 (4%) considered related to entecavir. There were 14 (1%) discontinuations due to AEs. On-treatment alanine aminotransferase (ALT) flares were reported in 32 (3%) patients and were associated with a reduction in hepatitis B virus DNA of more than 2 log10 copies/ml in 25/32 patients. AEs potentially associated with nucleos(t)ide analogs were infrequent, the most common being myalgia (n = 54; 5%) and neuropathy-related AEs (hypoparesthesia and hyperparesthesia, polyneuropathy; n = 42; 4%). Conclusions: Long-term administration of entecavir was associated with low rates of serious AEs, discontinuations due to AEs and ALT flares. AEs potentially associated with nucleos(t)ide use occurred at low rates. © 2012 Informa UK, Ltd.Gilead Sciences Novartis Pharma Novartis Bristol-Myers Squibb Merck GlaxoSmithKline, GSK Roche Bristol-Myers SquibbThe study was sponsored by Bristol-Myers Squibb. The sponsor designed the study in collaboration with expert hepatologists. The sponsor also collected the data, monitored study conduct, performed the statistical analyses and coordinated writing of the article with all authors. Medical writing assistance was provided by Esther Race of ArticulateScience and was funded by Bristol-Myers Squibb. A Pangerl, S Beebe, M Yu and S Wongcharatrawee are employees of Bristol-Myers Squibb. MP Manns has received grant support, consulting fees or honorarium from Merck, Roche, Bristol-Myers Squibb, Gilead, Novartis, GlaxoSmithKline; he has received grants from Merck, Roche, Gilead, Novartis and -- Bristol-Myers Squibb and has received payment for development of educational presentations from Merck, Roche, Bristol-Myers Squibb, GlaxoSmithKline, Novartis and Gilead. TT Chang received consulting fees or honorarium from Bristol-Myers Squibb. N Tsai received research grant support, consulting fees or honorarium from Bristol-Myers Squibb, USA. W Sievert, SK Yoon and A Min have no conflicts of interest to declare. -