Ingested IFN-α

Abstract

Objective: To investigate whether ingested human recombinant interferon-α2a (IFN-α2a) 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-α2a 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-α protein secretion at months 4 and 5. Relapses and adverse events were not different among the treatment groups. Ingested IFN-α2a did not induce systemic anti-IFN-α 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-α may deserve further study.