Damiano Baroncini1, Angelo Ghezzi2,3, Clara Guaschino2, Lucia Moiola4, Massimo Filippi5, Antonio Ianniello6, Carlo Pozzilli6, Roberta Lanzillo7, Vincenzo Brescia-Morra7, Monica Margoni8,9, Paolo Gallo8,9, Graziella Callari10, Luigi Grimaldi10, Giacomo Lus11, Massimiliano Calabrese12, Marta Simone13, Girolama Alessandra Marfia14, Sarah Rasia15, Daniela Cargnelutti16, Giancarlo Comi2,17, Mauro Zaffaroni2. 1. Multiple Sclerosis Center, Gallarate Hospital, ASST Valle Olona, Gallarate, VA, Italy. damianobaroncini@gmail.com. 2. Multiple Sclerosis Center, Gallarate Hospital, ASST Valle Olona, Gallarate, VA, Italy. 3. Dipartimento Di Scienze Della Salute, Università del Piemonte Orientale, Novara, Italy. 4. Multiple Sclerosis Center-Neurology Department, San Raffaele Hospital IRCCS, Milano, Italy. 5. Department of Neurology, Neurorehabilitation and Neurophysiology, MS Center, and Neuroimaging Research Unit, Vita-Salute San Raffaele University and San Raffaele Scientific Institute, Milan, Italy. 6. Department of Human Neurosciences, S.Andrea Multiple Sclerosis Center, Sapienza University, Rome, Italy. 7. Department of Neurosciences and Reproductive and Odontostomatological Sciences, University "Federico II", Naples, Italy. 8. Multiple Sclerosis Centre of the Veneto Region (CeSMuV), University Hospital of Padua, Padua, Italy. 9. Padova Neuroscience Centre (PNC), University of Padua, Padua, Italy. 10. Foundation Institute "G. Giglio", MS Center, Cefalù-Palermo, Italy. 11. Multiple Sclerosis Center, II Division of Neurology, Department of Clinical and Experimental Medicine, University of Campania "L. Vanvitelli", Naples, Italy. 12. Department of Neuroscience, Biomedicine and Movement, The Multiple Sclerosis Center of the University Hospital of Verona, Verona, Italy. 13. Child Neuropsychiatry Unit, Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro", Bari, Italy. 14. MS Clinical and Research Unit, Department of Systems Medicine, Tor Vergata University, Rome, Italy. 15. Multiple Sclerosis Center, ASST - Spedali Civili of Brescia, Montichiari, Brescia, Italy. 16. Neurology Unit, Udine University Hospital, Piazzale Santa Maria della Misericordia 15, 33100, Udine, Italy. 17. Casa Di Cura del Policlinico, Milan, Italy.
Abstract
BACKGROUND: Natalizumab (NAT) has a strong impact on disease activity of aggressive pediatric multiple sclerosis (MS), with no difference in safety profile compared to adult MS. However, available data are limited by short follow-up. Our aim was to report long-term follow-up data (up to 11 years) of a large Italian pediatric MS cohort treated with NAT. MATERIALS AND METHODS: We retrospectively collected data of pediatric MS patients treated with NAT included in a previous study and prospectively followed in Italian MS centers. We compared disease activity pre, during, and post-NAT and we performed survival analyses of time to evidence of disease activity (EDA) during NAT, time to reach EDA post-NAT, and time to NAT discontinuation. RESULTS: Ninety-two patients were included from 19 MS centers in Italy. At NAT initiation, cohort's characteristics were as follows: 55 females; 14.7 ± 2.4 (mean ± SD) years of age; 34 naïve to disease modifying therapies; 1-year pre-NAT annualized relapse rate (ARR): 2.2 ± 1.2; EDSS (median [IQR]): 2.5 [2.0-3.0]; gadolinium-enhancing lesions: 2 [1-5]; 41 JCV positives. During NAT treatment (61.9 ± 35.2 mean infusions), ARR lowered to 0.08 ± 0.23 (p < 0.001), EDSS score to 1.5 [1.0-2.5] at last infusion (p < 0.001), and 51% patients had EDA (21% after 6 months of rebaseline). No serious adverse events were reported. Forty-nine patients discontinued NAT, mainly due to PML concern; the majority (29/49) had disease reactivation in the subsequent 12 months, of which three with a clinical rebound. CONCLUSION: NAT treatment maintains its high efficacy for a long time in pediatric MS patients, with no new safety issues.
BACKGROUND: Natalizumab (NAT) has a strong impact on disease activity of aggressive pediatric multiple sclerosis (MS), with no difference in safety profile compared to adult MS. However, available data are limited by short follow-up. Our aim was to report long-term follow-up data (up to 11 years) of a large Italian pediatric MS cohort treated with NAT. MATERIALS AND METHODS: We retrospectively collected data of pediatric MS patients treated with NAT included in a previous study and prospectively followed in Italian MS centers. We compared disease activity pre, during, and post-NAT and we performed survival analyses of time to evidence of disease activity (EDA) during NAT, time to reach EDA post-NAT, and time to NAT discontinuation. RESULTS: Ninety-two patients were included from 19 MS centers in Italy. At NAT initiation, cohort's characteristics were as follows: 55 females; 14.7 ± 2.4 (mean ± SD) years of age; 34 naïve to disease modifying therapies; 1-year pre-NAT annualized relapse rate (ARR): 2.2 ± 1.2; EDSS (median [IQR]): 2.5 [2.0-3.0]; gadolinium-enhancing lesions: 2 [1-5]; 41 JCV positives. During NAT treatment (61.9 ± 35.2 mean infusions), ARR lowered to 0.08 ± 0.23 (p < 0.001), EDSS score to 1.5 [1.0-2.5] at last infusion (p < 0.001), and 51% patients had EDA (21% after 6 months of rebaseline). No serious adverse events were reported. Forty-nine patients discontinued NAT, mainly due to PML concern; the majority (29/49) had disease reactivation in the subsequent 12 months, of which three with a clinical rebound. CONCLUSION: NAT treatment maintains its high efficacy for a long time in pediatric MS patients, with no new safety issues.
Authors: L A Benson; B C Healy; M P Gorman; N F Baruch; T Gholipour; A Musallam; T Chitnis Journal: Mult Scler Relat Disord Date: 2013-07-12 Impact factor: 4.339
Authors: Natalie F Baruch; Ellen H O'Donnell; Bonnie I Glanz; Ralph H B Benedict; Alexander J Musallam; Brian C Healy; David Rintell; Tanuja Chitnis Journal: Mult Scler Date: 2015-06-03 Impact factor: 6.312
Authors: Laura Azzopardi; Sara A J Thompson; Katherine E Harding; Mark Cossburn; Neil Robertson; Alastair Compston; Alasdair J Coles; Joanne L Jones Journal: J Neurol Neurosurg Psychiatry Date: 2013-12-24 Impact factor: 10.154