BACKGROUND AND AIM: Natalizumab, used as therapy for multiple sclerosis (MS), has been associated with progressive multifocal leucoencephalopathy (PML), a potentially fatal disease caused by JC virus (JCV), which is not predictable by specific markers. This study evaluated whether JCV reactivation occurred in the urine and/or plasma in 42 MS patients treated with natalizumab over 18 months, and followed by a thorough monitoring programme. METHODS: 42 patients (F/M: 24/18, mean age 34.4±8.9 years) were followed-up by: urine and plasma JCV-DNA PCR assay, immune cell subsets analysis, clinical and MRI evaluation, quality of life, fatigue and mood assessment. RESULTS: JCV data. At baseline, 11/42 (26%) patients had JCV viruria, persistent at serial controls. One patient acquired viruria at month 1 and one patient at month 12. No patient had JCV viraemia at baseline; three patients acquired viraemic (one at month 6, one at month 13 (both transiently) and one at month 12 (persistently viraemic)). The prevalence of JCV in both urine and plasma did not change significantly from baseline to months 12 and 18. No patient had clinical or MRI evidence of PML. Immunological data. Circulating B cells showed greater expansion (300% increase in absolute number) since the first infusion. NK cell count doubled with no change in percentage while T cell count increased with a reduced percentage, reflecting a clear redistribution in the lymphocyte compartment. CD4+ and CD8+ T cells increased proportionally, with no change in their percentage. Clinical data. 27 patients (64%) were disease free after 1 year. A marked improvement in quality of life was reported by 72% of patients. CONCLUSIONS: No evidence of subclinical JCV reactivation was found in our natalizumab treated MS patients up to 18 months of therapy, notwithstanding the marked increase in circulating B cells observed. Moreover, the efficacy of natalizumab, its tolerability and the positive impact on quality of life were confirmed in this study.
BACKGROUND AND AIM: Natalizumab, used as therapy for multiple sclerosis (MS), has been associated with progressive multifocal leucoencephalopathy (PML), a potentially fatal disease caused by JC virus (JCV), which is not predictable by specific markers. This study evaluated whether JCV reactivation occurred in the urine and/or plasma in 42 MSpatients treated with natalizumab over 18 months, and followed by a thorough monitoring programme. METHODS: 42 patients (F/M: 24/18, mean age 34.4±8.9 years) were followed-up by: urine and plasma JCV-DNA PCR assay, immune cell subsets analysis, clinical and MRI evaluation, quality of life, fatigue and mood assessment. RESULTS:JCV data. At baseline, 11/42 (26%) patients had JCV viruria, persistent at serial controls. One patient acquired viruria at month 1 and one patient at month 12. No patient had JCV viraemia at baseline; three patients acquired viraemic (one at month 6, one at month 13 (both transiently) and one at month 12 (persistently viraemic)). The prevalence of JCV in both urine and plasma did not change significantly from baseline to months 12 and 18. No patient had clinical or MRI evidence of PML. Immunological data. Circulating B cells showed greater expansion (300% increase in absolute number) since the first infusion. NK cell count doubled with no change in percentage while T cell count increased with a reduced percentage, reflecting a clear redistribution in the lymphocyte compartment. CD4+ and CD8+ T cells increased proportionally, with no change in their percentage. Clinical data. 27 patients (64%) were disease free after 1 year. A marked improvement in quality of life was reported by 72% of patients. CONCLUSIONS: No evidence of subclinical JCV reactivation was found in our natalizumab treated MSpatients up to 18 months of therapy, notwithstanding the marked increase in circulating B cells observed. Moreover, the efficacy of natalizumab, its tolerability and the positive impact on quality of life were confirmed in this study.
Authors: Michael W Ferenczy; Leslie J Marshall; Christian D S Nelson; Walter J Atwood; Avindra Nath; Kamel Khalili; Eugene O Major Journal: Clin Microbiol Rev Date: 2012-07 Impact factor: 26.132
Authors: Jens Verheyen; Kseniya Maizus; Eugen Feist; Zebulon Tolman; Elena Knops; Jasemine Saech; Lydia Spengler; Tim Waterboer; Gerd R Burmester; Michael Pawlita; Herbert Pfister; Andrea Rubbert-Roth Journal: Med Microbiol Immunol Date: 2015-02-13 Impact factor: 3.402
Authors: Maria Inmaculada Dominguez-Mozo; Marta Garcia-Montojo; Virginia De Las Heras; Angel Garcia-Martinez; Ana María Arias-Leal; Ignacio Casanova; Rafael Arroyo; Roberto Alvarez-Lafuente Journal: J Neuroimmune Pharmacol Date: 2013-08-25 Impact factor: 4.147
Authors: Alice Laroni; Ilaria Gandoglia; Claudio Solaro; Giuseppe Ribizzi; Tiziana Tassinari; Matteo Pizzorno; Sergio Parodi; Giovanna Baldassarre; Maria Teresa Rilla; Simonetta Venturi; Elisabetta Capello; Maria Pia Sormani; Antonio Uccelli; Giovanni Luigi Mancardi Journal: BMC Neurol Date: 2014-05-12 Impact factor: 2.474