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ADEFOVIR FOR HBV- 144 WEEK FOLLOW-UP
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Reported by Jules Levin
"LONG TERM EFFICACY AND SAFETY OF ADEFOVIR DIPIVOXIL (ADV) 10 MG IN HBEAG+ CHRONIC HEPATITIS B (CHB) PATIENTS: INCREASING SEROLOGIC, VIROLOGIC AND BIOCHEMICAL RESPONSE OVER TIME"
Authors: P Marcellin, Hopital Beujon, Clichy, France; T T Chang, National Cheng Kung University Hospital, Tainan, Taiwan Republic of China; S Lim, National University Hospital, Singapore, Singapore; W Sievert, Monash Medical Centre, Victoria, Australia; M Tong, Huntington Medical Center Research Institute, Huntington, CA; Sarah Arterburn, Shelly Xiong, Carol L Brosgart, Graeme Currie, Gilead Sciences, Inc., Foster City, CA
3-year followup on adefovir for HBV was reported in a poster at the AASLD liver meeting (Oct 29-Nov 2, 2004) on HBeAg loss & seroconversion, ALT normalization, resistance & safety.
Approximately 400 million individuals worldwide have CHB, a leading cause of cirrhosis and HCC. ADV has potent activity against wild-type and lamivudine-resistant HBV. Treatment with ADV 10 mg over 48 wks demonstrated significant histological, virological, serological and biochemical improvement compared to placebo (PLB) in CHB. This study reports 144 week followup.
Patients were HBsAg+ >= 6 months, HBeAg+, serum HBV DNA >=106 c/mL (Roche Amplicor™ Monitor PCR, LLQ 1,000 c/mL) and ALT 1.2-10 x ULN.Adequate renal function. Prior interferon therapy allowed, if > 6 months prior to enrollment. Patients (pts) were randomized to receive ADV 10 mg or 30 mg, or PLB. The study continued to evaluate the long term safety and efficacy of ADV 10 mg in pts who received ADV 10 mg in the first 48 wks. Results are reported up to 144 wks of therapy.
Results
309 pts received >= 1 dose ADV 10 mg; 296, 231, and 84 pts were followed through 48, 96, and 144 wks; 74% male, 60% Asian and 35% Caucasian; median age 34 years. Baseline (BL) median serum HBV DNA 8.45 log10 c/mL; median ALT was 85-95 IU/L (2 x ULN). 7% had cirrhosis.
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Note: Pts with confirmed HBeAg seroconversion or HBeAg loss were followed off-treatment in an observational study
• Kaplan-Meier analysis
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The frequency and nature of adverse events (AEs), serious AEs and laboratory abnormalities was similar to PLB over 48 wks. Over 96 and 144 wks safety was consistent with that seen in the first 48 wks. Through 144 wks, no pt had a confirmed serum creatinine increase from BL of >= 0.5 mg/dL or a serum phosphorus < 1.5 mg/dL. No pt developed resistance by 48 wks; 2 (3.1%) developed resistance (1 N236T, 1 A181V) through 144 wks.
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The authors concluded that treatment with ADV 10 mg over 144 wks resulted in increasing HBeAg loss and seroconversion rates. Continued reductions in serum HBV DNA and ALT levels were demonstrated with increasing proportions of patients achieving undetectable serum HBV DNA and ALT normalization. Resistance was delayed and infrequent. ADV 10mg was well-tolerated with a safety profile consistent with that seen in PLB. No nephrotoxicity was observed. This study continues to evaluate the long term safety and efficacy of ADV 10 mg.
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