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Background and Objective: Our goal was to evaluate the relation between the presence of neutralizing antibodies (NABs) to interferon beta-1b in multiple sclerosis (MS) patients and the clinical evolution in the following years., Patients and Method: As we previously reported, we tested NABs in 68 patients treated with interferon beta-1b after 2 years of treatment. We prospectively followed this cohort every three months for a minimum period of 6 years collecting data about relapses, disability, secondary effects and dropouts., Results: During the 6 year follow-up period, the annualized relapse rate did not differ between patients with and patients without NABs. A sustained progression was observed in 33% of positive patients and in 38% of patients without NABs. No differences were found in the proportion of patients who reached an EDSS score of 6. Secondary effects were similar in both groups., Conclusions: Although our results do not vouch for a negative effect of the presence of NABs on the clinical evolution of MS patients treated with interferon beta, further longitudinal studies to clarify the real effect of the presence of NABs in these patients are still much needed.