THE INFLUENCE OF NEUTRALIZING ANTIBODIES TO INTERFERON-BETA ON PROGRESSION OF MULTIPLE SCLEROSIS

Abstract

Background: Neutralizing antibodies (NAbs) affect the effectiveness of interferon therapy in patients with multiple sclerosis; however, this influence cannot be considered as unequivocal. NAbs formation is determined by several factors, such as frequency and duration of administration, interferon-β (IFN-β) formulation and the patient's genotype. It has been found that NAb titers vary over time. Aim: To assess the levels of NAbs to IFN-β in patients with multiple sclerosis and to investigate their relationship to disease progression. Materials and methods: We analyzed serum samples from 83 multiple sclerosis patients after a long-term IFN-β-1b treatment; NAbs detection reaction was performed by assessment of their cytopathic effect. Results: NAbs were found in 63.9% (53 of 83) of patients with duration of IFN-β-1b treatment of 33.3±17.6 months. All NAb-positive patients were treated with highdose IFN-β. Patients with titers>800 LU (n=28) demonstrated a trend towards more advanced neurologic deficit on the Expanded Disability Status Scale (EDSS), compared to the patients with normal NAbs titers (0 to 20 LU, n=30) and intermediate titers (20 to 800 LU, n=25) (p>0.05). The exacerbation rate in the group with NAbs titers from 20 to 800 LU was insignificantly lower than that in the group with NAbs>800 and in the NAb-negative patients (p>0.05). Conclusion: Testing for NAbs may be a promising method for monitoring of IFN-β therapy in multiple sclerosis. There was a trend towards more pronounced neurological deficit in patients with high NAbs titers, but paradoxical data on a high rate of exacerbations in NAb-negative patients requires further study.

Keywords

• multiple sclerosis
• interferon-β
• neutralizing antibodies
• duration of treatment
• edss