Abstract
Natalizumab is highly effective in reducing multiple sclerosis disease activity; however it carries a risk of progressive multifocal leukoencephalopathy, that represents the main reason of drug discontinuation. After natalizumab withdrawal, reactivation of disease is soon observed and, until now, it is not known which treatment strategy should be followed after natalizumab discontinuation. Aim of this study is to evaluate rituximab efficacy in controlling disease activity after natalizumab withdrawal. Ten relapsing-remitting multiple sclerosis patients treated with natalizumab stopped it for the high risk of progressive multifocal leukoencephalopathy and started rituximab after a wash out period of two months; Second cycle of rituximab was planned in case of CD19+ cells increase and/or disease reactivation; brain MRI was performed before starting rituximab and then at six and twelve months after it. All the patients showed disease stability during the wash out period. Radiological stability was observed at 6 and at 12 months in all the patients; during the follow up two patients had exacerbation of sensitive symptoms without evidence of brain MRI activity. This study gives evidence of rituximab efficacy in abolishing disease reactivation after natalizumab withdrawal.
Highlights
Natalizumab is highly effective in reducing multiple sclerosis disease activity; it carries a risk of progressive multifocal leukoencephalopathy, that represents the main reason of drug discontinuation
A brain MRI performed six months after rituximab infusions did not show contrast-enhancing lesions or an increase in the number of T2 lesions compared to the brain MRI that had been performed after the last natalizumab infusion
No patient experienced clinical rebound; two out of ten had a worsening of pre-existing sensitive symptoms: the first patient had an exacerbation of paresthesia in left limbs six months after rituximab, the second had exacerbation of paresthesia in left face nine months after rituximab; both patients were treated with intravenous steroids for 3 days; in both cases CD19 at the time of clinical relapse were detectable and II cycle of rituximab was administered; brain MRI in both cases showed disease stability
Summary
This is a preliminary study, conducted on a small number of patients, aiming at the evaluation of rituximab efficacy after natalizumab withdrawal. Whatever regimen is adopted and despite the lower risk of PML, we believe that the use of rituximab to prevent breakthrough disease after natalizumab should be restricted to the first month after its discontinuation. Despite the small number of patients this study has two strong points: 1) patients had similar disease features before natalizumab initiation with very active course, and high risk of disease reactivation after its interruption; brain MRI were performed at the same time points with the same scanner and same protocol; 2) it shows rituximab appears an efficacious strategy to manage natalizumab discontinuation; we think our experience needs to be shared. Author details 1University Hospital San Luigi Gonzaga, SCDO Neurologia 2- Regional Multiple Sclerosis Center, Regione Gonzole 10, 10043 Orbassano, Torino, Italy. 2Dipartimento di Biomedicina Sperimentale e di Neuroscienze Cliniche, Università di Palermo, Via del Vespro 129, 90127 Palermo, Italy. 3Department of Neuroscience and Mental Health, Health and Science City, University Hospital of Turin, MS Center, I Neurologic Clinic, Via Cherasco 15, 10126 Torino, Italy
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