Neutralizing antibodies explain the poor clinical response to Interferon beta in a small proportion of patients with Multiple Sclerosis: A retrospective study

Background: Neutralizing antibodies (NAbs) against Interferon beta (IFN beta) are reported to be associated with poor clinical response to therapy in multiple sclerosis (MS) patients. We aimed to quantify the contribution of NAbs to the sub-optimal response of IFN beta treatment. Methods: We studied the prevalence of NAbs in MS patients grouped according to their clinical response to IFN beta during the treatment period. Patients were classified as: group A, developing >= 1 relapse after the first 6 months of therapy; group B, exhibiting confirmed disability progression after the first 6 months of therapy, with or without superimposed relapses; group C, presenting a stable disease course during therapy. A cytopathic effect assay tested the presence of NAbs in a cohort of ambulatory MS patients treated with one of the available IFN beta formulations for at least one year. NAbs positivity was defined as NAbs titre >= 20 TRU. Results: Seventeen patients (12.1%) were NAbs positive. NAbs positivity correlated with poorer clinical response (p < 0.04). As expected, the prevalence of NAbs was significantly lower in Group C (2.1%) than in Group A (17.0%) and Group B (17.0%). However, in the groups of patients with a poor clinical response (A, B), NAbs positivity was found only in a small proportion of patients. Conclusion: The majority of patients with poor clinical response are NAbs negative suggesting that NAbs explains only partially the sub-optimal response to IFN beta.