아데포비어의 안전성 및 유효성 평가를 위한 시판 후 조사

Post-Marketing Surveillance for the Safety and Effectiveness of Adefovir in Patients with Chronic Hepatitis B

  • 신근영 (경북대학교 의과전문대학원 내과학교실) ;
  • 최홍미 (글락소스미스클라인) ;
  • 오신영 (글락소스미스클라인) ;
  • 김준형 (글락소스미스클라인) ;
  • 이일섭 (글락소스미스클라인) ;
  • 권영오 (경북대학교 의과전문대학원 내과학교실)
  • 투고 : 2011.10.31
  • 심사 : 2011.12.26
  • 발행 : 2011.12.30

초록

Background: To investigate the safety and effectiveness of adefovir in Korean patients with chronic hepatitis B, an observational study was carried out. Methods: A total of 4,393 patients with chronic hepatitis B were enrolled from February 2004 to February 2010. For the safety assessment, investigators recorded the occurrence of observed and patient-reported adverse events (AEs) throughout the course of treatment. Antiviral effectiveness was assessed by measuring the degree of symptom improvement and the reduction of HBV DNA after 12 weeks of treatment. Results: Of the 4,393 patients, 4,158 patients were evaluated for safety and 3,867 patients for effectiveness assessment. A total of 118 AEs were reported in 4,158 patients (1.8 %). The most frequent AE was hepatic failure (0.2 %) followed by coughing (0.2 %), hepatic neoplasm (0.2 %), abdominal pain (0.1 %), dyspepsia (0.1 %), nausea (0.1 %), flatulence (0.1 %), hepatic cirrhosis (0.1 %), asthenia (0.1 %), increase in sputum production (0.1 %), and varicose vein (0.1 %). The incidence of unexpected AEs was 0.9 %. Forty-nine cases of serious AE were reported in 32 patients but all of those were thought to be unrelated to adefovir according to physician's evaluations. The rate of subjects with well effectiveness was 96.2 %. Conclusion: Adefovir was clinically well tolerated and effective in treatment of chronic hepatitis B patients.

키워드

과제정보

연구 과제 주관 기관 : GSK

참고문헌

  1. Kao JH, Chen DS. Global control of hepatitis B virus infection. Lancet Infect Dis, 2002;2(7):395-403. https://doi.org/10.1016/S1473-3099(02)00315-8
  2. Lee WM. Hepatitis B virus infection. N Engl J Med, 1997;337:1733-1745. https://doi.org/10.1056/NEJM199712113372406
  3. Lok AS. Navigating the maze of hepatitis B treatments. Gastroenterology, 2007;132(4):1586-1594. https://doi.org/10.1053/j.gastro.2007.02.040
  4. Dienstag JL, Schiff ER, Wright TL, Perrillo RP, Hann HW, Goodman Z, Crowther L, Condreay LD, Woessner M, Rubin M, Brown NA. Lamivudine as initial treatment for chronic hepatitis B in the United States. N Engl J Med, 1999;341:1256-1263. https://doi.org/10.1056/NEJM199910213411702
  5. Lok AS, Lai CL, Leung N, Yao GB, Cui ZY, Schiff ER, Dienstag JL, Heathcote EJ, Little NR, Griffiths DA, Gardner SD, Castiglia M. Long-term safety of lamivudine treatment in patients with chronic hepatitis B. Gastroenterology, 2003;125(6):1714-1722. https://doi.org/10.1053/j.gastro.2003.09.033
  6. Liaw YF, Leung NW, Chang TT, Guan R, Tai DI, Ng KY, Chien RN, Dent J, Roman L, Edmundson S, Lai CL. Effects of extended lamivudine therapy in Asian patients with chronic hepatitis B. Asia Hepatitis Lamivudine Study Group. Gastroenterology, 2000;119(1):172-180. https://doi.org/10.1053/gast.2000.8559
  7. Chin R, Shaw T, Torresi J, Sozzi V, Trautwein C, Bock T, Manns M, Isom H, Furman P, Locarnini S. In vitro susceptibilities of wild-type or drug-resistant hepatitis B virus to (-)-beta-D-2,6-diaminopurine dioxolane and 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil. Antimicrob Agents Chemother, 2001;45(9):2495-2501. https://doi.org/10.1128/AAC.45.9.2495-2501.2001
  8. Lee KS and Kim DJ. Management of Chronic Hepatitis B. Korean J Hepatol, 2007;13(4):447-488. (Korean) https://doi.org/10.3350/kjhep.2007.13.4.447
  9. Lampertico P, Vigano M, Manenti E, Iavarone M, Sablon E, Colombo M. Low resistance to adefovir combined with lamivudine: a 3-year study of 145 lamivudine-resistant hepatitis B patients. Gastroenterology, 2007;133(5):1445-1451. https://doi.org/10.1053/j.gastro.2007.08.079
  10. Benhamou Y, Bochet M, Thibault V, Calvez V, Fievet MH, Vig P, Gibbs CS, Brosgart C, Fry J, Namini H, Katlama C, Poynard T. Safety and efficacy of adefovir dipivoxil in patients co-infected with HIV-1 and lamivudine-resistant hepatitis B virus: an open-label pilot study. Lancet, 2001;358(9283):718-723. https://doi.org/10.1016/S0140-6736(01)05840-8
  11. Marcellin P, Chang TT, Lim SG, Tong MJ, Sievert W, Shiffman ML, Jeffers L, Goodman Z, Wulfsohn MS, Xiong S, Fry J, Brosgart CL; Adefovir Dipivoxil 437 Study Group. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. N Engl J Med, 2003;348:808-816. https://doi.org/10.1056/NEJMoa020681
  12. Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, Marcellin P, Lim SG, Goodman Z, Wulfsohn MS, Xiong S, Fry J, Brosgart CL; Adefovir Dipivoxil 438 Study Group. Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B. N Engl J Med, 2003;348:800-807. https://doi.org/10.1056/NEJMoa021812
  13. Kahn J, Lagakos S, Wulfsohn M, Cherng D, Miller M, Cherrington J, Hardy D, Beall G, Cooper R, Murphy R, Basgoz N, Ng E, Deeks S, Winslow D, Toole JJ, Coakley D. Efficacy and safety of adefovir dipivoxil with antiretroviral therapy: a randomized controlled trial. JAMA, 1999;282(24):2305-2312. https://doi.org/10.1001/jama.282.24.2305
  14. Izzedine H, Hulot JS, Launay-Vacher V, Marcellini P, Hadziyannis SJ, Currie G, Brosgart CL, Westland C, Arterbrun S, Deray G; Adefovir Dipivoxil International 437 Study Group; Adefovir Dipivoxil International 438 Study Group. Renal safety of adefovir dipivoxil in patients with chronic hepatitis B:two double-blind, randomized, placebo-controlled studies. Kidney Int, 2004;66:1153-1158. https://doi.org/10.1111/j.1523-1755.2004.00866.x
  15. Marcellin P, Chang TT, Lim SG, Sievert W, Tong M, Arterburn S, Borroto-Esoda K, Frederick D, Rousseau F. Long-term efficacy and safety of adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. Hepatology, 2008;48(3):750-758. https://doi.org/10.1002/hep.22414
  16. Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, Marcellin P, Lim SG, Goodman Z, Ma J, Brosgart CL, Borroto-Esoda K, Arterburn S, Chuck SL; Adefovir Dipivoxil 438 Study Group. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. Gastroenterology, 2006;131(6):1743-1751. https://doi.org/10.1053/j.gastro.2006.09.020