Is the treatment effect of IFN-beta restored after the disappearance of neutralizing antibodies?

Abstract

OBJECTIVE:

To establish whether multiple sclerosis (MS) patients, who have lost the therapeutic effect of interferon-beta (IFN-beta) owing to neutralizing antibodies (NAbs) and subsequently revert from a NAb-positive to a NAb-negative state under continued IFN-beta-1b therapy, regain clinical effect after reversion.

BACKGROUND:

Several studies have shown that a significant proportion of patients treated with IFN-beta develop NAbs that hamper or abolish the therapeutic effect of IFN-beta. However, some patients, who become NAb-positive under treatment with IFN-beta-1b, may revert to a NAb-negative state under continuous treatment.

METHODS:

We identified 40 patients from the Danish IFN protocol, who fulfilled the criteria: NAb-positive status for at least 12 months followed by reversion to NAb-negative state for at least 12 months. For comparison, we included 64 matching cases that had remained NAb-negative during an observation time of at least 36 months. The two groups were clinically and demographically alike. We measured NAb-neutralizing capacity using a clinically validated cytopathic effect assay. A blood sample with a neutralizing capacity of 20% or more was considered as NAb-positive. A patient was defined as NAb-positive after two consecutive blood tests separated by at least 6 months. Reversion to a NAb-negative state required at least two consecutive negative tests. To allow for the confounding effect of time we employed a mixed Poisson model.

RESULTS:

Patients who had been NAb-positive and reverted to a NAb-negative state regained treatment effect with the relapse rate as before the NAb-positive period adjusting for the effect of time, and the relapse rate was the same as in the permanently NAb-negative patients in corresponding time periods. The relapse rate ratio comparing the NAb-positive with the NAb-negative periods was 1.98 (95% confidence interval: 1.32-2.97).

CONCLUSION:

Under NAb-positive periods, the clinical effect of IFN-beta was abolished. When NAbs disappeared spontaneously under continued treatment, patients regained the full effect of INF-beta-1b therapy with no negative carry-over effect from the previous NAb-positive period.

• Authors: P S Sorensen, N Koch-Henriksen, E M Flachs, K Bendtzen
• Journal: Multiple sclerosis (Houndmills, Basingstoke, England) (Mult Scler) Vol. 14 Issue 6 Pg. 837-42 (Jul 2008) ISSN: 1352-4585 [Print] England
• PMID: 18505772 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Antibodies
• Interferon beta-1b
• Interferon-beta

Topics

• Adjuvants, Immunologic (administration & dosage)
• Adolescent
• Adult
• Antibodies (blood)
• Female
• Humans
• Interferon beta-1b
• Interferon-beta (administration & dosage, immunology)
• Male
• Middle Aged
• Multiple Sclerosis (drug therapy, immunology)
• Neutralization Tests
• Poisson Distribution
• Recurrence
• Treatment Outcome