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Background and Purpose Patients treated with interferon-beta (IFN-β) can develop neutralizingantibodies (NAbs) against IFN-β that can negatively affect the therapeutic response. This study assessed the prevalence of NAbs and the impact of NAb positivity on the therapeuticresponse to IFN-β in Korean patients with multiple sclerosis (MS). Methods This was a multicenter study involving 150 MS patients from 9 Korean medicalcenters who were treated with IFN-β for at least 6 months. Sera that had not been influencedby acute treatment were assessed for NAbs using a luciferase reporter gene assay. To evaluatethe association between persistent positivity for NAbs and disease activity, NAbs were tested at2 different time points in 75 of the 150 patients. Disease activity was defined as the presence ofclinical exacerbations and/or active MRI lesions during a 1-year follow-up after NAb positivitywas confirmed. Results NAbs were found in 39 of the 150 (26%) MS patients: 30 of the 85 (35%) who weretreated with subcutaneous IFN-β-1b, 9 of the 60 (15%) who were treated with subcutaneousIFN-β-1a, and 0 of the 5 (0%) who were treated with intramuscular IFN-β-1a. Thirty of the 39patients exhibiting NAb positivity were tested at different time points, and 20 of them exhibitedpersistent NAb positivity. Disease activity was observed more frequently in patients with persistentNAb positivity than in those with transient positivity or persistent negativity [16/20 (80%)vs. 4/55 (7%), respectively; p<0.001]. When disease activity was compared between patientswith persistent and transient NAb positivity, the difference was unchanged and remained statisticallysignificant [16/20 (80%) vs. 2/10 (20%), p=0.004]. Conclusions These results further support that persistent NAb positivity is associated withdisease activity in MS patients treated with IFN-β.

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