Prolonged efficacy and safety of 3 years of continuous telbivudine treatment in pooled data from globe and 015 studies in chronic hepatitis B patients

Abstract

Background and Aims: Telbivudine demonstrated superior efficacy vs lamivudine in adults with HBeAg-positive and HBeAg-negative CHB in the GLOBE and 015 studies. Most of the patients from these studies continued on telbivudine treatment in a 2-year extension trial (2303). The pooled (GLOBE and 015) efficacy and safety results for 3 years of telbivudine treatment are presented. Methods: 530 telbivudine-treated patients without genotypic resistance at the end of the core studies were enrolled into 2303 without study drug discontinuation. Of these patients, 496 (94%) completed 3 years of therapy, 7 (1%) of patients discontinued treatment due to efficacy and 27 (5%) discontinued therapy due to other reasons. The per protocol population of 503 patients was considered for this analysis. Results: At 3 years, among 293 HBeAg-positive patients, 75% had undetectable HBV DNA (<300 copies/mL) and 83% had ALT normalization. 55% of patients obtained HBeAg loss and 39% achieved HBeAg seroconversion, while 4 (2%) patients lost HBsAg and 1 patient had HBsAg seroconversion. Higher rates of PCR negativity (87%) and seroconversion (47%) were achieved at 3 years in patients who had undetectable HBV DNA at week 24 of the core studies. The cumulative seroconversion rate for 3 years was 54% and even higher − 70% − for patients with ALT levels 2 x ULN and HBV DNA levels <9 log10 copies/mL at GLOBE study baseline. Of the 210 HBeAg-negative patients, 85% had undetectable HBV DNA and 84% had ALT normalization at 3 years. The telbivudine safety profile was similar to the 2-year results. CK elevation was reported in 10%, myalgia in 4%, muscular weakness in 0.6%, and myositis in 0.4%. Rate of peripheral neuropathy (including paresthesia, neuralgia, polyneuropathy and sensory loss) was low (1.2%). No cases of rhabdomyolysis, lactic acidosis or other new safety signals were observed with continued telbivudine treatment to 3 years. Conclusions: Over 3 years, telbivudine treatment provides effective viral suppression and ALT normalization in HBeAg-positive and HBeAgnegative CHB patients with a favorable safety profile. In HBeAg-positive patients, telbivudine treatment achieves a high cumulative seroconversion rate, especially in patients with baseline characteristics predictive of good outcome.