자료실


Long-term Entecavir Treatment Safe and Effective in Japanese Treatment-Naive Chronic Hepatitis B Patients Through Year 3

Posting Date: April 29, 2008

Summary of Key Conclusions

  • Entecavir 0.5 mg/day shown safe, effective through 3 years in treatment-naive chronic hepatitis B patients from Japan
    • 87% of patients achieved HBV DNA < 400 copies/mL
    • 91% of patients achieved ALT normalization
    • HBeAg seroconversion occurred in 23% of patients
    • Fibrosis improved in 63% of patients
    • No deaths occurred
    • Low treatment discontinuation rate (4.4%)
  • Low cumulative probability of genotypic entecavir resistance or entecavir resistance with virologic breakthrough at Year 3 in patients receiving the approved 0.5 mg/day dosage (1.7%)

Background

  • Entecavir and FDA-approved nucleoside analogue treatment for chronic hepatitis B patients
    • Potent antiviral activity, high barrier to resistance in long-term treatment demonstrated in previous studies of treatment-naive patients
  • Japanese study, ETV-047, illustrated entecavir 0.5 mg/day superior to lamivudine 100 mg/day in reducing HBV DNA following 24 weeks of treatment[2]
  • High rates of HBV DNA suppression and ALT normalization in response to entecavir 0.5 mg/day over 48 weeks in Japanese study ETV-053[3]
  • ETV-060, rollover study of ETV-047, ETV-053 participants
  • Current study examined long-term efficacy, safety, and resistance profiles associated with entecavir 0.5 mg/day treatment in nucleoside-naive chronic hepatitis B patients

Summary of Study Design

  • Analysis of treatment-naive chronic hepatitis B patients receiving entecavir 0.5 mg daily from 3 Japanese studies (ETV-047, ETV-053, ETV-060)
    • 68 patients from ETV-047 and ETV-053 included in cohort, and 66 rolled over to ETV-060
      • 32 patients from ETV-047, 34 from ETV-053
      • Enrollment into ETV-060 immediately following conclusion of either study with no interruption in treatment
    • Combined duration of entecavir treatment up to 148 weeks in ETV-053 participants, 144 weeks in ETV-047 participants
  • Eligibility for enrollment into ETV-047 or ETV-053
    • Chronic hepatitis B patients with compensated liver disease
    • HBV DNA
      • ≥ 5 log10 copies/mL in study ETV-053
      • ≥ 7.6 log10 copies/mL in study ETV-047
    • ALT < 1.25 x upper limit of normal (ULN), > 10 x ULN
    • ≤ 12 weeks previous nucleoside analogue therapy
  • Parameters evaluated through Week 148
    • HBV DNA change from baseline
      • Measured by PCR assay
    • Undetectable HBV DNA (< 400 copies/mL)
    • ALT ≤ 1.0 x ULN
    • HBeAg seroconversion
    • Virologic breakthrough and resistance
    • Histologic improvement according to Knodell score
  • Analysis of adverse events, treatment discontinuations, mortality conducted

Baseline Characteristics

Characteristic

Long-term, Treatment-Naive Japanese Cohort
(N = 68)

Male, %

72

Mean age, yrs

43.2

Mean weight, kg

65.4

Japanese, %

100

HBV DNA log10 copies/mL
± SD

8.03 ± 0.93

Mean ALT, IU/L ± SD

141.7 ± 86.5

HBeAg positive, %

84

HBV genotype C, %

95.6

Mean Knodell score ± SE

 

  • Fibrosis

2.57 ± 0.23

  • HAI

8.95 ± 0.65

HAI, hepatic activity index; SD, standard deviation; SE, standard error.

Main Findings

  • 87% of nucleoside-naive chronic hepatitis B patients achieved HBV DNA < 400 copies/mL after 3 years of entecavir treatment

Parameter, %

Week 24

Week 72/76

Week 144/148

Undetectable HBV DNA

50

75

87

ALT normalization

78

86

91

HBeAg seroconversion

9

18

23

  • 16/16 patients with Knodell necroinflammatory score 7-14 at baseline reduced to necroinflammatory scores < 7 by Year 3 of treatment
  • Fibrosis scores reduced in 63% of patients by study end
  • Cumulative probability of entecavir resistance or entecavir resistance with subsequent virologic breakthrough at Year 3 in patients receiving entecavir 0.5 mg/day (1.7%)  
    • Lamivudine resistance mutation L180M and M204V and entecavir resistance mutation S202G

Other Outcomes

  • Entecavir 0.5 mg/day well tolerated through 3 years
    • Although all participants reported at least 1 adverse event, only 4% forced to discontinue treatment
    • No deaths

Parameter, %

Long-term, Treatment-Naive Japanese Cohort
 (N = 68)

Any adverse event

100

Grade 3-4 AE

 

  • Clinical

8.8

  • Laboratory

14.7

Serious AE

20.6

Discontinuation due to adverse event

4.4

ALT flare*

4.4

*ALT flare = ALT > 2 x baseline and > 10 x ULN.

  • Most common clinical adverse events
    • Nasopharyngitis: 80.9%
    • Upper abdominal pain: 22.1%
    • Diarrhea: 22.1%
    • Headache: 22.1%
    • Pharyngolaryngeal pain: 19.1%
  • Some patients in initial studies ETV-047 and ETV-063 had received lower dosages of entecavir (0.01 or 0.10 mg/day)
    • Among these patients receiving less than the approved dosage of drug, 4 developed genotypic resistance by Year 3 evaluation
      • All had lamivudine resistance mutations M204V and L180M
      • 3 also had entecavir resistance mutation S202G, whereas the other patient had entecavir resistance mutation T184A

References

1. Mochida S, Takaguchi K, Yososuka, O et al. Long term efficacy, safety and resistance analyses of entecavir (ETV) treatment in Japanese nucleoside-naive patients with chronic hepatitis B (CHB). Program and abstracts of the 43rd Annual Meeting of the European Association for the Study of the Liver; April 23-27, 2008; Milan, Italy. Abstract 703.

2. Shindo M, Chayama K, Toyota J, et al. Efficacy and safety of entecavir and lamivudine in japanese adult patients with chronic hepatitis B infection: a phase 2 clinical trial. J Clin Virol. 2006;36:S94-S95.

3. Takaguchi K, Kita K, Ikeda H, et al. Anti-viral activity, histologic improvement and safety of entecavir in Japanese adult nucleoside-analogue naive patients with chronic hepatitis B infection: a phase 2 clinical trial. J Clin Virol. 2006;36:S96.

번호 제목 글쓴이 날짜 조회 수
» Long-term Entecavir Treatment Safe and Effective in Japanese Treatment-Naive Chronic Hepatitis B Patients Through Year 3 [2] 양전호 2008.05.26 1074
130 소아에서의 B형,C형간염치료 [8] 양전호 2008.05.08 1229
129 건강복지공동회의 토론회 발표문 (2007-9-17) [1] file 윤구현 2008.05.01 715
128 암 검진 질 지침. 국립암센터. [3] file 윤구현 2008.04.10 844
127 국가인권위원회 B형간염에 관한 사건 결정문 4건 [2] file 윤구현 2008.03.30 1488
126 장애 및 병력을 이유로한 차별 진정사건 접수 및 처리 통계현황(2007) 국가인권위원회 [1] file 윤구현 2008.03.30 711
125 2007년12월31일 기준 공공의료기관 현황 [1] file 윤구현 2008.03.02 737
124 시드니 성건강센터에서 만든 한국어로 된 A형간염에 대한 안내문 [1] file 윤구현 2008.02.25 792
123 호주 정부에서 만든 한국어로 된 B형간염접종 안내문 [2] file 윤구현 2008.02.25 837
122 2007년 암검진 행태 조사 결과 [1] file 윤구현 2008.02.25 654
121 심평원 심사사례(2008.2.)-C형간염페가시스치료, 제픽스내성에서 헵세라 처방에 대한 심사사례 [1] file 윤구현 2008.02.25 741
120 심평원 심사사례(2007.10.)-제픽스 내성 환자에게 레보비르 처방은 비급여 [1] file 윤구현 2008.02.25 735
119 최근 B형간염 경구용제제의 치료성적 update [2] 양전호 2008.01.27 1933
118 AASLD 2007 미국간학회 만성B형 간염 경구제 항바이러스제제 치료에 대한 발표내용 [1] 양전호 2008.01.22 1018
117 2007 미국간학회 만성B형간염 가이드라인 [1] file 윤구현 2008.01.21 1122
116 2007년 대한간학회 만성B형간염치료 가이드라인 [2] file 윤구현 2008.01.11 1676
115 B형간염치료제의 보험급여 확대와 가격인하 [11] file 윤구현 2008.01.02 2030
114 B형간염에 대한 용어 정의 [18] 윤구현 2007.12.22 6745
113 여성에서의 간질환 최신지견 General Hepatology Update: Unique Aspects of Liver Disease Management in Women, Norah Terrault, MD [1] 양전호 2007.12.11 768
112 건강검진실시기준개정 [4] file 윤구현 2007.12.02 1443