title: Monthly corticosteroids decrease neutralizing antibodies to IFNbeta1 b: a randomized trial in multiple sclerosis.
abstract: Neutralizing antibodies (NAB) to interferon beta (IFNbeta) 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 IFNbeta-1 b with that in patients treated with IFNbeta-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 IFNbeta- 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 > or = 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 IFNbeta-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 IFNbeta-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.o49 for definition II, by the Wilcoxon-Gehan test). Methylprednisilone combined with IFNbeta-1 b reduces the incidence of neutralizing bodies to in terferon-beta during the first year of treatment in MS patients.
authors.affiliation: Department of Neurological Sciences, University La Sapienza, Rome, Italy. carlo.pozzilli@uniroma1.it
authors.forename: Carlo
authors.initials: C
authors.lastname: Pozzilli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Antonini
authors.forename: Francesca
authors.initials: F
authors.lastname: Bagnato
authors.forename: Caterina
authors.initials: C
authors.lastname: Mainero
authors.forename: Valentina
authors.initials: V
authors.lastname: Tomassini
authors.forename: Emanuela
authors.initials: E
authors.lastname: Onesti
authors.forename: Roberta
authors.initials: R
authors.lastname: Fantozzi
authors.forename: Simona
authors.initials: S
authors.lastname: Galgani
authors.forename: Patrizio
authors.initials: P
authors.lastname: Pasqualetti
authors.forename: Enrico
authors.initials: E
authors.lastname: Millefiorini
authors.forename: Maria
authors.initials: M
authors.lastname: Spadaro
authors.forename: Frank
authors.initials: F
authors.lastname: Dahlke
authors.forename: Claudio
authors.initials: C
authors.lastname: Gasperini
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000819:agonists*; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000009:adverse effects*; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D000906:Antibodies / Q000097:blood / Q000187:drug effects* / Q000276:immunology; D015536:Down-Regulation / Q000187:drug effects* / Q000276:immunology; D004334:Drug Administration Schedule; D004347:Drug Interactions / Q000502:physiology; D004359:Drug Therapy, Combination; D004361:Drug Tolerance / Q000502:physiology; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000009:adverse effects / Q000819:agonists*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D055502:Secondary Prevention; D013256:Steroids; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D000906:Antibodies; D013256:Steroids; D000068576:Interferon beta-1b; D016899:Interferon-beta; D000068556:Interferon beta-1a