CHRONIC SYSTEMIC HIGH-DOSE RECOMBINANT INTERFERON ALFA-2A REDUCES EXACERBATION RATE, MRI SIGNS OF DISEASE-ACTIVITY, AND LYMPHOCYTE INTERFERON-GAMMA PRODUCTION IN RELAPSING-REMITTING MULTIPLE-SCLEROSIS

We report a randomized, double-blind, placebo-controlled pilot trial o f systemic high-dose recombinant interferon alfa-2a (rIFNA) in 20 pati ents with relapsing-remitting (RR) multiple sclerosis (MS). Patients r eceived 9 million IU rIFNA (n = 12) or placebo (n = 8) intramuscularly every other day for 6 months. Clinical exacerbations or new or enlarg ing lesions on serial MRI occurred in two of 12 rIFNA-treated and in s even of eight placebo-treated patients (p < 0.005). There was only one enlarging MRI lesion in the rIFNA group, whereas 27 new or enlarging lesions were present in the placebo group (p < 0.0 1). Baseline lympho cyte interferon gamma production of 19.10 +/- 7.12 IU/ml significantly decreased to 3.03 +/- 0.66 IU/ml (p < 0.04) in the rIFNA group, where as production was unchanged in the placebo group. The rIFNA was tolera ted without dropouts or serious side effects, but fever, malaise, fati gue (interfering with daily activities in two patients), and leukopeni a occurred frequently. Neuropsychological tests excluded neurotoxicity . High-dose systemic rIFNA might reduce clinical and MRI signs of dise ase activity in RR MS and should be investigated in larger trials.