BRIVUDIN COMPARED TO FAMCICLOVIR IN THE PREVENTION OF POSTHERPETIC NEURALGIA: A RANDOMIZED, DOUBLE-BLIND MULTICENTER TRIAL

*S. W. Wassilew (1), K. Schumacher (2), G. Stätdler (2), I. Koch (2), A. Capriati (3), B.M. Stubinski (2), on behalf of the Collaborative Brivudin PHN Study Group
(1) Dermatologic Department, Klinikum Krefeld, Germany; (2) Berlin-Chemie / Menarini Group, Berlin, Germany; (3) Menarini Ricerche, Florence, Italy

Objective:
To determine the efficacy and safety of brivudin in the prevention of postherpetic neuralgia (PHN) and in shortening zoster associated pain (ZAP) in comparison with famciclovir.
Design: A randomized, double-blind, multicenter, non-inferiority trial with a 7-day treatment period and a follow-up of at least 3-1/2 and up to 9 months, depending on the presence of ZAP. Patients who had ZAP of at least moderate intensity (> 3 of the WHO score 0 - 10) three months after start of treatment were defined as having PHN. Only immunocompetent patients > 50 years of age were enrolled. Treatment had to start within 72 hours of rash onset. All patients were offered structured analgesic treatment following modified WHO recommendations of step by step grading (1-3) for the management of pain.
Patients:
2,027 patients from 188 centers were analyzed (brivudin: N=1,019, famciclovir: N=1,008). Baseline characteristics were comparable in both treatment groups. 1,954 patients were assessable for PHN.
Treatments:
Oral brivudin 125 mg once daily vs. oral famciclovir 250 mg three times daily.
Results:
Primary endpoint:
In the PP population (N=1,712), 98 brivudin patients (11.3 %) and 81 famciclovir patients (9.6 %) had PHN at month 3 (Odds ratio: 1.20, CI: 0.877-1.635, P for non inferiority=0.01). In the ITT population the prevalence of PHN was 11.1% under brivudin and 9.2% under famciclovir (N=1954; OR: 1.23, CI: 0.92-1.65, P=0.01).
Secondary endpoints:
The mean duration of PHN (PP population) was 59.3 days under brivudin and 68.5 days under famciclovir (OR: 1.11, CI: 0.74-1.65, P=0.31).
Further secondary parameters included prevalence, duration, and intensity of ZAP, the analysis of which revealed comparable treatment effects of both treatments. Adverse events with a possible, probable, or not assessable relationship to study medication occurred in 11.8% of the brivudin patients and in 10.1% of the famciclovir patients.
Conclusion:
Brivudin is as effective as famciclovir in preventing PHN and speeding the resolution of ZAP and PHN. The once daily treatment schedule with brivudin is particularly advantageous in elderly patients with increasing drug intake and at high risk of developing chronic pain. The safety profile of brivudin is good and well comparable to that of famciclovir.

Corresponding Author: Prof. Dr. S. W. Wassilew, Director of the Dermatologic Department, Klinikum Krefeld, Lutherplatz 40, 47805 Krefeld, Germany