Damiano Paolicelli1, A Manni2, A Iaffaldano2, V Di Lecce2, M D'Onghia2, P Iaffaldano2, M Trojano2. 1. Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari Aldo Moro, Policlinico, Piazza Giulio Cesare 11, 70124, Bari, Italy. damiano.paolicelli@uniba.it. 2. Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari Aldo Moro, Policlinico, Piazza Giulio Cesare 11, 70124, Bari, Italy.
Abstract
PURPOSE: During interferon-β (IFN-β) therapy, up to 45 % of patients may develop neutralizing antibodies (NAbs), associated with a decreased efficacy of the drug. We investigated in a real-life setting the impact of NAbs on magnetic resonance imaging (MRI) outcomes in a population of 567 IFN-β-treated relapsing-remitting (RR) multiple sclerosis (MS) patients up to 7 years. We also evaluated NAbs' role as a biomarker of the persistence of MRI disease activity. METHODS: Patients' sera were tested for NAbs' presence by cytopathic effect (CPE) assay every 6-12 months. MRI scans were performed every 12 months. Generalized hierarchical linear models accounting for within-patient correlation were used to analyze T1 gadolinium-enhancing and new T2 lesions. Moreover, further tests were carried out to assess the overall outcome difference from year 1 to year 7 according to NAb status and the possible interaction between NAb status and time of follow-up. RESULTS: Seventy-five patients (13.2 %) became NAb positive (NAb+) during the follow-up. Considering T1 gadolinium-enhancing (GD+) lesions, we observed a significantly higher incidence in NAb+ patients (52 %, p = 0.0091). Also for new T2 lesions, we found a higher incidence in NAb+ patients (50 %, p = 0.0075). The negative impact of NAbs on the MRI outcomes considered did not change during the follow-up. CONCLUSIONS: Our 7-year results show the negative effect of NAbs on MRI measures of disease activity and confirm their role as a surrogate marker of IFN-β treatment efficacy.
PURPOSE: During interferon-β (IFN-β) therapy, up to 45 % of patients may develop neutralizing antibodies (NAbs), associated with a decreased efficacy of the drug. We investigated in a real-life setting the impact of NAbs on magnetic resonance imaging (MRI) outcomes in a population of 567 IFN-β-treated relapsing-remitting (RR) multiple sclerosis (MS) patients up to 7 years. We also evaluated NAbs' role as a biomarker of the persistence of MRI disease activity. METHODS:Patients' sera were tested for NAbs' presence by cytopathic effect (CPE) assay every 6-12 months. MRI scans were performed every 12 months. Generalized hierarchical linear models accounting for within-patient correlation were used to analyze T1 gadolinium-enhancing and new T2 lesions. Moreover, further tests were carried out to assess the overall outcome difference from year 1 to year 7 according to NAb status and the possible interaction between NAb status and time of follow-up. RESULTS: Seventy-five patients (13.2 %) became NAb positive (NAb+) during the follow-up. Considering T1 gadolinium-enhancing (GD+) lesions, we observed a significantly higher incidence in NAb+ patients (52 %, p = 0.0091). Also for new T2 lesions, we found a higher incidence in NAb+ patients (50 %, p = 0.0075). The negative impact of NAbs on the MRI outcomes considered did not change during the follow-up. CONCLUSIONS: Our 7-year results show the negative effect of NAbs on MRI measures of disease activity and confirm their role as a surrogate marker of IFN-β treatment efficacy.
Entities:
Keywords:
Biomarkers; Interferon-β; MRI disease activity; Multiple sclerosis; Neutralizing antibodies; Real life
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