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

OBJECTIVE: 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 log(10) 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.