Anti-interferon-beta antibodies in Polish multiple sclerosis patients: prevalence and clinical significance in a long-term prospective study.

AIM OF THE STUDY: To determine the prevalence of anti-interferon-ß binding (BAb) and neutralising antibodies (NAb), and to investigate whether NAb measured by luciferase-based cell assay can predict treatment response in multiple sclerosis (MS) patients treated with interferon-ß-1b (IFNß-1b). CLINICAL RATIONALE FOR THE STUDY: A subgroup of IFNß-treated MS patients develop NAb directed against the drug. The clinical significance remains controversial, which could be explained to some extent by technical difficulties in NAb detection and quantification. A simple, specific and reproducible test for NAb might help elucidate these uncertainties. MATERIALS AND METHODS: Sera from 101 consecutive MS patients initiating treatment with IFNß-1b were collected at baseline and during the first two years, and assessed for BAbNAb with a novel luciferase-based cell assay. Median clinical follow-up lasted 5.1 years. RESULTS: BAb were present in 97% and NAb in 88% of the study cohort. Unexpectedly, 92% of patients tested positive for Bab and 12.5% for NAb at baseline, before drug exposure. Patients with baseline NAb positivity were more likely to remain free of disease activity in the first three years of treatment. When baseline-positive cases were grouped together with those who remained NAb-negative, and the resulting group was compared to those who became positive after drug exposure, NAb positivity was associated with a higher risk of disease activity during the entire follow-up. Direct comparison of BAb/Nab-positive and BAb/Nab-negative patients only revealed an association of BAb positivity with more active disease after four years of treatment, while NAb failed to predict the outcome. CONCLUSIONS AND CLINICAL IMPLICATIONS: Antibodies developed after treatment initiation are associated with a worse outcome. Naturally- occurring antibodies appear to predict more benign disease. Their prevalence and specificity require further investigation.