Monthly corticosteroids decrease neutralizing antibodies to IFNβ1b: a randomized trial in multiple sclerosis

Abstract

Neutralizing antibodies (NAB) to interferon beta (IFNβ) occur in some multiple sclerosis (MS) patients, particularly during the first year of treatment. The presence of NAB may be associated with an attenuation of the therapeutic effect. The aim of this study was to compare the frequency of NAB occurrence in patients treated with IFNβ-1 b with that in patients treated with IFNβ-1 b combined with monthly pulses of intravenous methylprednisolone (MP).

One hundred and sixty-one patients with relapsing-remitting MS were randomized in two treatment arms: 8 MIU of IFNβ-1 b subcutaneously injected every other day either alone or in combination with 1000 mg of monthly intravenous MP.

NAB were evaluated at baseline and at months 3, 6, 9, 12 and 15 by the MxA assay in a specialized laboratory. Positivity was defined as a titer of ≥ 20 neutralizing units according to two different definitions: I) one or more non-consecutive positive samples, II) at least two consecutive positive samples.

NAB (definition I) were observed in 26.8 % of patients in the IFNβ-1 b alone arm and in 12.1 % of patients in the combination therapy arm (p=0.05 by the chi-square test), which corresponds to a relative reduction of 54.9 %, whereas according to definition II, these figures dropped to 22.5 % for the IFNβ–1 b alone arm, and 10.6 % for the combination therapy arm (relative reduction 52.9 %, p=0.10, NS). A higher probability of remaining in the NAB-free status was observed in patients treated with the combination therapy (p=0.031 for definition I and p=0.049 for definition II, by the Wilcoxon-Gehan test).

Methylprednisilone combined with IFNβ-1 b reduces the incidence of neutralizing bodies to interferon-β during the first year of treatment in MS patients.