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ETV Re-treatment of Nucleoside-Naive HBeAg(-) Patients with Recurrent Viremia
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Reported by Jules Levin
EASL, April 11-15, 2007, Barcelona, Spain
H. Senturk1, Y. Lurie2, A. Gadano3, C.K. Tan4, T. Tran5, SD Lee6, N. Tsai7, H. Cheinquer8, J.Yang9, R. Tamez10, and R. Hindes9
1Cerrahpasa Medical Faculty, Istanbul, Asksaray, Turkey; 2Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; 3Hospital Italiano, Buenos Aires, Argentina; 4Department of Gastroenterology, Singapore General Hospital, Singapore; 5Cedars Sinai Hospital, Los Angeles, USA;
6Taipei Veterans General Hospital, Taipei, Taiwan; 7University of Hawaii, Honolulu, HI; 8Universidade Federal Do Rio Grande Do Sul, Porto Alegre, Brazil; 9Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, USA; 10Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, USA
AUTHOR CONCLUSIONS
Contrary to current clinical practice, ETV-027 study design mandated the majority of patients discontinue study therapy after 52 weeks of treatment
During off-treatment follow-up the majority of patients had recurrent viremia and increases in ALT
48 weeks of ETV re-treatment in the Nucleoside-Naive HBeAg(-) ETV Re-treatment Cohort resulted in:
- 93% achieving HBV DNA <300 copies/mL
- 83% achieving ALT normalisation
The safety profile remains consistent with the previously reported experience.
Introduction
Entecavir (ETV) 0.5 mg was superior to lamivudine (LVD) 100 mg for virological, histological and biochemical endpoints at Week 48 in nucleosidenaive, HBeAg(-) chronic hepatitis B (CHB) patients (ETV-027).1
According to protocol-defined criteria, the majority of ETV- and LVD-treated patients discontinued therapy at Week 52 and were followed offtreatment for 24 weeks (Figure 1).
We evaluated the effect of 48 weeks of ETV re-treatment in rollover study ETV-901 (1 mg) in ETV-treated patients from study 027.
Methods
Nucleoside-Naive HBeAg(-) ETV Re-treatment Cohort
- The Nucleoside-Naive HBeAg(-) ETV Re-treatment Cohort evaluated here consisted of 99 patients (Figure 2):
- Initially treated with ETV in ETV-027
- Subsequently enrolled in ETV-901 with >60 day gap in treatment between ETV-027 and ETV-901
- This analysis cohort was defined regardless of:
- Treatment response at end of dosing in ETV-027
- HBV DNA or ALT measurements at the start of dosing in ETV-901
Treatment
Initially, due to ongoing blinding of study ETV-027, patients re-treated in ETV-901, received a combination of ETV 1 mg and LVD 100 mg a day.
Subsequently, patients were switched to receive ETV 1 mg.
Evaluations
Patients in the Nucleoside-Naive HBeAg(-) ETV Re-treatment Cohort were assessed at Weeks 12, 24, 36 and 48 after re-initiation of treatment.
Nucleoside-Naive HBeAg(-) ETV Re-treatment Cohort analyses are based on observed values for proportions of patients with:
- HBV DNA <300 copies/mL (by PCR)
- ALT normalization (≦1 x ULN )
Safety was analysed for all patients in the Nucleoside-Naive HBeAg(-)
ETV Re-treatment Cohort.
In the Nucleoside-Naive HBeAg(-) ETV Re-treatment Cohort:
- Mean HBV DNA was 6.64 log10 copies/mL (by PCR) [vs. 7.6 log10 copies/mL in ETV-027)
- Mean ALT was 222 U/L [vs. 141 U/L in ETV-027]
HBV DNA
94% of patients in the Nucleoside-Naive HBeAg(-) ETV Re-treatment Cohort achieved HBV DNA <300 copies/mL by EOD in ETV-027 (Figure 4).
The majority of patients experienced recurrent viremia during the off-treatment follow-up period.
In the Nucleoside-Naive HBeAg(-) ETV Re-treatment Cohort:
-- 83% of patients achieved HBV DNA <300 copies/mL by Week 24
-- 93% of patients achieved HBV DNA <300 copies/mL by Week 48
Overall, ETV was well-tolerated (Table 2).
All subjects who experienced an on-treatment ALT flare had at least a 2 log10 reduction from entry in HBV DNA that was sustained for the duration of the flare.
No deaths or discontinuations due to AEs were reported in the Nucleoside-Naive HBeAg(-) ETV Re-treatment Cohort.
The safety profile of the Nucleoside-Naive HBeAg(-) ETV Re-treatment Cohort in ETV-901 was consistent with previously reported experience.
ALT
78% of patients in the Nucleoside-Naive HBeAg(-) ETV Re-treatment Cohort achieved ALT normalization by EOD in ETV-027 (Figure 6).
The majority of patients experienced an increase in ALT toward baseline
levels (or higher) during the off-treatment follow-up period.
In the Nucleoside-Naive HBeAg(-) ETV Re-treatment Cohort:
-- 75% of patients achieved ALT normalization by Week 24
-- 83% of patients achieved ALT normalization by Week 48
References
1. Lai CL, et al. N Engl J Med. 2006;354:1011-1020
2. Shouval D, et al. Journal of Hepatology 2006; 44(Supplement 2): S21
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