Ingested IFN-alpha: results of a pilot study in relapsing-remitting MS.
OBJECTIVE
To investigate whether ingested human recombinant interferon-alpha2a (IFN-alpha2a) was safe and whether treatment reduces the number of gadolinium-enhanced lesions on serial MRI in patients with active relapsing-remitting MS (RRMS).


METHODS
Entry criteria included clinically definite RRMS and one or more gadolinium-enhanced lesions on a screening MRI.


RESULTS
Of 80 patients screened, 33 were eligible and 30 patients were enrolled for treatment. Patients were randomized (10 per group) to placebo, 10,000 or 30,000 IU IFN-alpha2a ingested on alternate days for 9 months. They were examined clinically and with monthly cerebral MRI. Sample size projections were based on the assumption of a parenteral IFN-like effect, a 90% reduction of enhancing lesions evident within 1 month of the initiation of treatment in the active treatment groups sustained during the 9-month study as the primary outcome variable.


RESULTS
There was no significant effect on enhancing lesions. However, post hoc analysis suggested a possible treatment effect in the 10,000 IU group. By direct monthly comparison of placebo and 10,000 IU group in treatment month 5, there were 73% (p < 0.05) fewer enhancements in the 10,000 IU group than in the placebo group. There was a decrease of tumor necrosis factor-alpha protein secretion at months 4 and 5. Relapses and adverse events were not different among the treatment groups. Ingested IFN-alpha2a did not induce systemic anti-IFN-alpha antibodies.


CONCLUSIONS
This trial showed no benefit based on the primary outcome measure. Because changes were detected in immune response and post hoc analysis suggested that a smaller dose could have an effect, IFN-alpha may deserve further study.
Brod
S A
SA
Department of Neurology, University of Texas-Houston, 77225, USA. Staley.A.Brod@uth.tmc.edu
Lindsey
J W
JW
Vriesendorp
F S
FS
Ahn
C
C
Henninger
E
E
Narayana
P A
PA
Wolinsky
J S
JS
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D001921:Brain / Q000187:drug effects / Q000473:pathology; D004311:Double-Blind Method; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D007370:Interferon Type I / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D017063:Outcome Assessment, Health Care; D010865:Pilot Projects; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007155:Immunologic Factors; D007370:Interferon Type I; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha