Neutralizing antibodies reduce the efficacy of betaIFN during treatment of multiple sclerosis.

Abstract

OBJECTIVE:

To analyze the impact of neutralizing antibodies (NAbs) on the clinical efficacy of IFNbeta.

METHODS:

This was an open-label study involving 78 patients with multiple sclerosis treated with Betaferon 8 million IU (MIU) subcutaneously (SC) every other day (n = 20), Rebif 22 micro g SC 3 times weekly (n = 25), or Avonex 30 micro g IM once weekly (n = 33). Every 3 months, blood samples were collected and sera were analyzed for NAbs using an antiviral cytopathic effect assay. Patients were categorized according to their NAb status: NAb negative (NAb-); isolated NAb positive (NAb+), patients with > or =1 positive sample (titer > or = 20); and persistent NAb+, patients with > or =2 consecutive positive samples (titer > or = 20). Patients who were NAb- and persistent NAb+ were compared for relapse rate, time between first and second relapse, percentage of relapse-free patients, and percentage of patients who had a sustained progression of > or =1 point on the Expanded Disability Status Scale (EDSS).

RESULTS:

The incidence of persistent NAb+ patients was 35% for Betaferon, 20% for Rebif, and 3% for Avonex. During IFNbeta treatment, both NAb+ and NAb- patients showed a reduction in relapse rate; this reduction (25%) was not significant in NAb+ patients but was significant (67%; p < 0.0001) in NAb- patients. In addition, the mean relapse rate was higher (p = 0.039), mean time between first and second relapse was shorter (13 vs 21 months; p = 0.0064), and there was a trend suggesting that NAbs affected the probability of remaining relapse free (p = 0.08). A higher percentage of NAb+ patients versus NAb- patients had worsening of EDSS scores during follow-up (p = 0.013).

CONCLUSION:

Persistent NAbs significantly reduce the clinical efficacy of IFNbeta.

• Authors: S Malucchi, A Sala, F Gilli, R Bottero, A Di Sapio, M Capobianco, A Bertolotto
• Journal: Neurology (Neurology) Vol. 62 Issue 11 Pg. 2031-7 (Jun 08 2004) ISSN: 1526-632X [Electronic] United States
• PMID: 15184610 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Isoantibodies
• Interferon beta-1b
• Interferon-beta
• Interferon beta-1a

Topics

• Adolescent
• Adult
• Aged
• Antibody Specificity
• Antiviral Agents (immunology, pharmacology)
• Cell Line, Tumor
• Cytopathogenic Effect, Viral (drug effects)
• Disease Progression
• Disease-Free Survival
• Drug Resistance
• Encephalomyocarditis virus (drug effects, physiology)
• Female
• Follow-Up Studies
• Humans
• Incidence
• Interferon beta-1a
• Interferon beta-1b
• Interferon-beta (antagonists & inhibitors, immunology, pharmacology, therapeutic use)
• Isoantibodies (immunology)
• Life Tables
• Male
• Middle Aged
• Multiple Sclerosis, Relapsing-Remitting (drug therapy, immunology)
• Neutralization Tests
• Prospective Studies
• Severity of Illness Index
• Treatment Outcome