한국인 만성 B형간염 환자에 대한 텔비부딘의 효능 및 안전성
The Efficacy and Safety of Telbivudine in Korean Patients with Chronic Hepatitis B
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배경: 텔비부딘은 L-nucleoside 유사체로 HBV에 대하여 강력한 억제 효과를 보인다. 임상시험을 통해 텔비부딘은 라비부딘에 비하여 유의하게 강력한 항바이러스 효과를 보여주었다. 이번 연구를 통해 3상 임상시험에 참여하였던 한국인 환자에 대한 텔비부딘의 효능과 안전성을 알아보고자 하였다. 방법: 다국가 3상 임상시험에 참여했던 1,367명의 만성 B형간염 환자 중 한국인 환자 101명의 52주 결과를 분석하였다. 101명의 환자들은 HBeAg 유무에 관계없이 텔비부딘 일일 600 mg 복용군 또는 라미부딘 일일 100 mg 복용군에 무작위로 배정되었다. 5 log10 copies/mL 미만으로 혈청 HBV DNA 억제가 있으면서 ALT 정상화 또는 HBeAg 양성 환자의 경우 HBeAg 소실로 정의되는 치료 반응(therapeutic response)을 1차 효능 결과 변수로 정의하였다. 이차 효능 변수로 조직 반응(histologic response), HBV DNA의 감소, ALT 정상화, HBeAg 양성 환자의 경우 HBeAg의 소실을 살펴보았다. 결과: 총 101명의 환자 중 54명이 텔비부딘 복용군에 배정되었고, 47명이 라미부딘 복용군에 포함되었다. 52주 투여 결과 텔비부딘 복용군에서 라미부딘에 비하여 유의하게 많은 환자들이 치료반응에 도달하였고(83% 대 62%, P=0.017), 혈청 HBV DNA 감소(6.6 대 5.6 log10 copies/mL, P= 0.027)와 HBV DNA의 PCR 불검출률(74% 대 34%, P<0.0001)에서도 유의한 차이를 보였다. 또한 텔비부딘 복용군은 바이러스 내성(0% 대 18%, P=0.001)이 52주까지 관찰되지 않았다. 텔비부딘의 내약성은 우수하였고 라미부딘과 유사한 안전성을 보였다. 결론: 한국인 만성 B형간염 환자 중 텔비부딘을 복용한 환자들이 라미부딘 복용군에 비하여 유의하게 신속하고 강력한 항바이러스 효과를 보여주었다. 텔비부딘 복용군에서 바이러스 돌파현상은 관찰되지 않았고 두 약제의 안전성은 동등하였다.
Abstract
Background/Aims: Telbivudine is an L-nucleoside analogue with potent antiviral activity against hepatitis B virus (HBV). Clinical trials have shown that telbivudine is more potent than lamivudine for suppressing virus. Methods: A total 101 Korean patients among 1,367 patients who participated in the phase III GLOBE trial were randomized in this study. All 101 HBeAg positive or HBeAg negative patients were assigned to treatment with 600 mg of telbivudine or 100 mg of lamivudine once daily. The primary efficacy endpoint (the “therapeutic response”) was defined as suppression of the serum HBV DNA to less than 5 log10 copies/mL coupled with either normalization of the serum alanine aminotransferase level or loss of HBeAg. The secondary endpoints included the histologic response, serum HBV DNA reduction, serum alanine aminotransferase normalization and HBeAg loss for the HBeAg positive patients. This analysis includes the data collected at 52 weeks of treatment. Results: Fifty four of 101 patients were assigned to telbivudine treatment and 47 patients were assigned to lamivudine treatment. At week 52, significantly more patients who were treated with telbivudine than those treated with lamivudine had a therapeutic response (83% vs 62%, respectively, P=0.017), their mean serum HBV DNA levels were more reduced (6.6 vs 5.6 log10 copies/mL, respectively, P=0.027), and they more often achieved PCR-undetectable levels of serum HBV DNA (74% vs 34%, P<0.0001). No virologic resistance to telbivudine was detected (0% vs 18%, respectively, P=0.001). Telbivudine was well tolerated and it had a safety profile comparable to lamivudine. Conclusions: Patients treated with telbivudine achieved earlier and more profound viral suppression than those treated with lamivudine.
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