ACYCLOVIR TREATMENT OF RELAPSING-REMITTING MULTIPLE-SCLEROSIS - A RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND-STUDY

Acyclovir treatment was used in a randomized, double-blind, placebo-co ntrolled clinical trial with parallel groups to test the hypothesis th at herpes virus infections are involved in the pathogenesis of multipl e sclerosis (MS). Sixty patients with the relapsing-remitting form of MS were randomized to either oral treatment with 800 mg acyclovir or p lacebo tablets three times daily fur 2 years. The clinical effect was investigated by an extensive test battery consisting of neurological e xaminations, neuro-ophthalmological and neuropsychological tests, and evoked potentials. Results were based on ''intent-to-treat'' data and the primary outcome measure was the exacerbation rate. In the acyclovi r group (n = 30), 62 exacerbations were recorded during the treatment period, yielding an annual exacerbation rate of 1.03. The placebo grou p (ii = 30) had 94 exacerbations and an annual exacerbation rate of 1. 57. Thus, 34% fewer exacerbations were encountered during acyclovir tr eatment. This difference in exacerbation rate between the treatment gr oups was not significant (P = 0.083). However, this trend to a lower d isease activity in acyclovir-treated patients was supported in subsequ ent data analysis. If the patients were grouped according to exacerbat ion frequencies, i.e. into low (0-2), medium (3-5) and high (6-8) rate groups, the difference between acyclovir and placebo treatment was si gnificant (P = 0.017). Moreover, in a subgroup of the population with a duration of the disease of at least 2 years providing an exacerbatio n rate base-line before entry, individual differences in exacerbation rates were compared between the 2-year pre-study period and the study period in acyclovir-treated (it = 19) and placebo (ii = 20) patients a nd acyclovir-treated patients showed a significant reduction of exacer bations (P = 0.024). Otherwise, neurological parameters were essential ly unaffected by acyclovir treatment and there were no convincing sign s of reduced neurological deterioration in the acyclovir group. This s tudy indicates that acyclovir treatment might inhibit the triggering o f MS exacerbations and thus suggests that acyclovir-susceptible viruse s might be involved in the pathogenesis of MS. This possibility warran ts further investigation.