Background & Aims
This study investigated the antiviral efficacy and safety of telbivudine in combination with pegylated interferon (PegIFN) alpha-2a in chronic hepatitis B (CHB) patients.

Methods
This was a randomized, open-label, multicentre study, in treatment-naïve patients with HBeAg-positive CHB, comparing the efficacy and safety of telbivudine in combination with PegIFN alpha-2a with telbivudine monotherapy and PegIFN alpha-2a monotherapy. The study was terminated early due to increased rates of peripheral neuropathy in the combination-therapy group.

Results
Of the 159 patients randomized (from 300 planned) 50 were assigned to combination therapy, 55 to telbivudine, 54 to PegIFN, and 110 (18, 49, and 43, respectively) reached week 24. Peripheral neuropathy occurred in 7/50, 1/54, and 0/54 patients in the three groups of safety populations, respectively. No relationship between the occurrence of peripheral neuropathy and other variables (e.g., pharmacokinetic data, treatment efficacy, ALT levels, creatine kinase elevations) were observed. At week 24, undetectable HBV DNA (<300 copies/ml) was achieved by 71% (12/17), 35% (17/48), and 7% (3/42) of patients, with available data receiving combination therapy, telbivudine monotherapy and PegIFN monotherapy, respectively (p = 0.022 for combination therapy vs. telbivudine; p <0.0001 for combination therapy vs. PegIFN).

Conclusions
Combination therapy carried an increased risk of peripheral neuropathy. Despite the rapid and profound reductions in HBV DNA levels, combination therapy with telbivudine and PegIFN should not be used

La découverte de cet effet secondaire survient dans le cadre de la recherche d’une optimisation de la prise en charge de l’infection chronique par le VHB qui passe notamment par des essais de bithérapie, associant l’interféron et d’autres molécules (telbivudine, ténofovir ….) ; ces résultats doivent nous inciter à rester particulièrement vigilant lors de ces essais aux risques d’émergence d’une iatrogénie.