title: 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.
abstract: We report a randomized, double-blind, placebo-controlled pilot trial of systemic high-dose recombinant interferon alfa-2a (rIFNA) in 20 patients with relapsing-remitting (RR) multiple sclerosis (MS). Patients received 9 million IU rIFNA (n = 12) or placebo (n = 8) intramuscularly every other day for 6 months. Clinical exacerbations or new or enlarging lesions on serial MRI occurred in two of 12 rIFNA-treated and in seven 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 < 0.01). Baseline lymphocyte 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, whereas production was unchanged in the placebo group. The rIFNA was tolerated without dropouts or serious side effects, but fever, malaise, fatigue (interfering with daily activities in two patients), and leukopenia occurred frequently. Neuropsychological tests excluded neurotoxicity. High-dose systemic rIFNA might reduce clinical and MRI signs of disease activity in RR MS and should be investigated in larger trials.
authors.affiliation: Clinica delle Malattie del Sistema Nervoso, Università di Torino, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Durelli
authors.forename: M R
authors.initials: MR
authors.lastname: Bongioanni
authors.forename: R
authors.initials: R
authors.lastname: Cavallo
authors.forename: B
authors.initials: B
authors.lastname: Ferrero
authors.forename: R
authors.initials: R
authors.lastname: Ferri
authors.forename: M F
authors.initials: MF
authors.lastname: Ferrio
authors.forename: G B
authors.initials: GB
authors.lastname: Bradac
authors.forename: A
authors.initials: A
authors.lastname: Riva
authors.forename: S
authors.initials: S
authors.lastname: Vai
authors.forename: M
authors.initials: M
authors.lastname: Geuna
mesh_terms: D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D007371:Interferon-gamma / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000276:immunology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D011994:Recombinant Proteins; D012008:Recurrence
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D007371:Interferon-gamma