2-YEAR RESULTS OF TELBIVUDINE (LDT) ROADMAP STUDY VERIFY THE OPTIMAL EFFICACY AND SAFETY RESULTS IN HBEAG POSITIVE CHRONIC HEPATITIS B (CHB) PATIENTS

Abstract

Background and Aims: The roadmap concept based on Week 24 HBV DNA levels was prospectively validated with 1year results of Roadmap study (A2410) as previously reported. The 2 year results are reported here. Patients and Methods: All patients were HBeAg positive and started LDT monotherapy from baseline and Tenofovir (LDT) was added to patients with detectable (≥300 copies/ml) HBV DNA at 24w until 104w. Results: 105 patients were enrolled and 100 patients were eligible for modified ITT (mITT) analysis (1 patient with baseline M204I mutation, 2 lost follow-up and 2 didn’t follow roadmap concept). At 24w, 55 patients achieved undetectable HBV DNA and 45 patients with detectable HBV DNA added with TDF (73% of the 45 patients with baseline HBV DNA > 9log10 copies/ml). At 104w, 94% had undetectable HBV DNA, 50%/44% HBeAg loss/seroconversion, 7%/4% HBsAg loss/seroconversion. One patient in LDT mono-treated arm had Virologic Breakthrough (VB) at Week 72 and detected M204I mutation; achieved undetectable HBV DNA 8wks after TDF add-on. One LDT mono-treated patient had one time of HBV DNA increase of 1 log10 above nadir (assessment ongoing). Both patients had baseline HBV DNA > 9log10 copies/ml. In the overall safety population, Serious Adverse Events (SAEs) was reported in 6/105 (5.7%) patients and all unrelated to treatment. No case of myopathy/myositis was reported. Overall GFR (by MDRD formula) improvement was +6.4 and +8.6ml/min/1.73m2 in LDT mono and LDT+TDF group respectively. In patients with abnormal baseline GFR (60–90ml/min/1.73m2), GFR improvement at 2yr was +12.0 and +1.5ml/min/1.73m2 in LDT and LDT+TDF respectively. 50% and 40% of patients with abnormal baseline GFR (60–90ml/min/1.73m2) in LDT and LDT+TDF group respectively shifted to normal (>90ml/min/1.73m2) at 2yr. Only 1 patient in TDF add-on group had once creatinine increase to 232 μmol/L at Week 96, and returned to 91 μmol/L within 4 days. Conclusion: Telbivudine roadmap with tenofovir add-on at 24 weeks in patients with detectable HBVDNA improved GFR in both LDT and LDT+TDF treated patients, as well as favorable efficacy and safety profiles.