Prospective, Randomized Safety Assessment of Long- Term Therapy With Entecavir or Other Nucleos(t)ide An alogues in Korean Patients with Chronic HBV Infection = Prospective, Randomized Safety Assessment of Long- Term Therapy With Entecavir or Other Nucleos(t)ide An alogues in Korean Patients with Chronic HBV Infection

다국어 초록 (Multilingual Abstract)

Aims: REALM was a prospective, randomized, open-label, observational study, conducted to assess rates of long-term clinical outcomes in patients with CHB who were treated with entecavir (ETV) or other standard-of-care HBV nucleos(t)ide analogues (nuc). Korean sub-analysis was conducted to investigate any significant differences on clinical outcomes and safety profiles in Korean subjects.
Methods: Treatment-naive or -experienced Korean patients with CHB were randomly assigned (1:1) to monotherapy with ETV (0.5 mg or 1.0 mg once daily per product label) or a non- ETV nuc (specific agent investigator-selected) and followed for ≤10 years. Clinical outcome events (COEs) were reported by investigators, reviewed and adjudicated by an Events Adjudication Committee (EAC). Primary endpoints were rates of adjudicated COEs including 1) malignant neoplasms (composite of non-hepatocellular carcinoma [HCC] and HCC); 2) liver-related HBV disease progression (composite of non-HCC HBV disease progression, HCC, and liver-related death); and 3) all-cause death. Secondary endpoints were adjudicated COE rates of non-HCC malignant neoplasms, HCC, and liver-related death. An exploratory endpoint was the adjudicated COE rate of non- HCC HBV disease progression. Treatment-related serious adverse events (SAEs) were also assessed.
Results: Patients were randomized and treated to receive ETV (n=1243) or non-ETV (n=1239). Overall, at baseline, 63% were HBeAg+ and 37% had cirrhosis.. Mean time on study was 91 (ETV) and 86 (non-ETV) months. There were no statistically significant differences in COE rates between treatment groups (Table). Results were consistent in baseline subgroups. Treatment-related SAEs that were not protocol-defined COEs were reported in 2 (0.2%) ETV and 26 (2.1%) non-ETV patients, with spectra as expected.
Conclusions: This large, long-term study found no statistically significant differences in COE rates between Korean patients randomized to ETV vs non-ETV nuc monotherapy, and the results of Korean sub-analysis were consistent with the results from entire REALM study subjects. SAEs were uncommon al-though higher in the non-ETV group.