BRIVUDIN COMPARED TO ACYCLOVIR IN THE TREATMENT OF ACUTE HERPES ZOSTER: A RANDOMIZED; DOUBLE-BLIND, MULTICENTER TRIAL

*P. Wutzler (1), B.M. Stubinski (2), I. Koch (2), G. Städtler (2), K. Schumacher (2), on behalf of the Collaborative Brivudin Herpes Zoster Study Group (1) Institute for Antiviral Chemotherapy, Erfurt, (2) Berlin-Chemie / Menarini Group, Berlin, Germany

Study objective:
To determine the efficacy and safety of brivudin in comparison with acyclovir in patients with herpes zoster.
Design: Randomized, double-blind, multicenter trial with a 7-day
treatment period and follow-up of up to 1 month.
Setting:
303 centers in 15 countries.
Patients:
1,227 immunocompetent patients with acute herpes zoster, aged 18 years or older received treatment with brivudin (N=614) or acyclovir (N=613).
Baseline characteristics were comparable in the two treatment groups. The study was terminated prematurely by 18 brivudin and 21 acyclovir patients. Treatments: Oral brivudin 125 mg once daily versus oral acyclovir 800mg five times daily, both for 7 days. Treatment started within 48 hours after first vesicular eruption.
Main Results:
The confirmatory analysis "time from start of treatment to the last eruption of new vesicles" showed superiority of brivudin compared to acyclovir (ITT population, N=1,124, Risk ratio: 1.13, P=0.01). The result holds for the subpopulation of patients = 50 years of age (N=754, RR: 1.16, P=0.02). In patients with new with vesicle formation after start of treatment (N=637), the mean time to the stop of new vesicle formation was 27.9 hours with brivudin and 32.3 hours with acyclovir, also showing superiority of brivudin (RR: 1.16, P=0.03). The time to resolution of acute pain was the same for both drugs (RR: 0.99). For the PP population overall similar results were observed. Adverse events occurred in 23% of the brivudin patients and 22 % of the acyclovir patients. Of these, 8% (brivudin) and 10% (acyclovir) were assessed as probably/possibly attributable to study medication by the investigator. Conclusions: Brivudin 125 mg offers an effective and safe treatment of acute herpes zoster with only one daily drug intake. Compared to acyclovir, treatment with brivudin results in a significantly faster stop of viral replication, particularly in older patients who are at a higher risk of
developing postherpetic neuralgia. The safety profile of brivudin is good and well comparable to that of acyclovir.

Corresponding author: Professor Peter Wutzler, Institute for Antiviral Chemotherapy, Nordhäuser Str. 78, D-99089 Erfurt, Germany.