Switching therapy from natalizumab to fingolimod in relapsing-remitting multiple sclerosis: Clinical and magnetic resonance imaging findings
Multiple Sclerosis Centre of Padova, University Hospital, Italy.Multiple Sclerosis (Impact Factor: 4.82). 11/2012; 18(11):1640-3. DOI: 10.1177/1352458512464282
Clinical and/or neuroimaging evidence of disease reactivation has been described in multiple sclerosis (MS) patients after a break from natalizumab. Whether fingolimod might be a therapeutic option following natalizumab needs to be evaluated. Twenty-two relapsing remitting MS patients having JC virus antibodies (JCVAb+) in serum were shifted from natalizumab to fingolimod after a three-month washout period. Neurological evaluation with the Expanded Disability Status Scale (EDSS) was performed monthly for a mean follow-up period of nine months. In 20/22 patients, brain magnetic resonance imaging (MRI) was obtained within one month after therapy initiation. Disease reactivation was observed in 11/22 (50%) patients: clinical relapses in six patients (four patients within the first month of therapy) and MRI activity in a further five patients (three patients within the first month of therapy). Clinical and/or MRI signs suggestive of disease rebound were observed in three patients. Our data indicate that fingolimod does not exert clinical activity quickly enough to stop MS reactivation after a break from natalizumab.
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- "The longer the patient waits to start FTY, the higher the chance of a relapse will be. A summary from a comprehensive review of the literature on the subject of relapses and disability (as assessed by the expanded disability scale score, EDSS), relating to the switch between NTZ and FTY, is presented in Table 1181920212223242526272829303132333435. Longer washout periods have consistently been correlated with higher risk of disease reactivation. "
ABSTRACT: Natalizumab is a therapeutic option for treating multiple sclerosis (MS) and is particularly efficacious for patients with highly active disease. A long washout period has been recommended between withdrawal of natalizumab and start of fingolimod (another option for treating MS). This long washout period has been associated with a significant increase in MS activity. In the present study, a group of 96 patients who were switched from natalizumab to fingolimod had short washout periods between drugs, or monthly corticosteroid pulse therapy if longer washout periods were recommended. This therapeutic approach led to the lowest reported relapse rate so far, among patients with MS switching from natalizumab to fingolimod (8.3%). No complications from short withdrawal were observed in this group of patients.
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- "It is interesting to note that, 21 months after her last natalizumab infusion, the patient has not developed any clinical or MRI findings suggesting re-appearance of MS activity. This is in contrast to several reports showing reactivation of MS within 15 months after the cessation of natalizumab treatment in 50% or more of cases  . "
ABSTRACT: A multiple sclerosis (MS) patient developed progressive multifocal leukoencephalopathy (PML) after 43months of natalizumab treatment. New clinical and magnetic resonance imaging (MRI) findings were initially misinterpreted as breakthrough MS disease activity and natalizumab treatment was replaced by rituximab treatment. The patient had a single infusion of rituximab 1000mg before a definite PML diagnosis was confirmed. Despite undetectable levels of B-cells, JC virus DNA became undetectable in the cerebrospinal fluid by quantitative polymerase chain reaction. The patient partially recovered without any clinical or MRI signs of new MS activity. These findings suggest that B-cell depletion in a non-immune compromised individual did not prevent the patient from clearing the JC virus infection. Copyright © 2015 Elsevier B.V. All rights reserved.
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- "The effect of fingolimod in preventing disease reactivation after natalizumab discontinuation has been evaluated by a number of small size observational studies (Rinaldi et al., 2012; Havla et al., 2013; Laroni et al., 2013; Sempere et al., 2013). Two of them (Havla et al., 2013; Laroni et al., 2013) suggested patients who switched to fingolimod within 6 months after natalizumab had reduced annualized relapse rates compared with those who remained untreated or who switched to intramuscular interferon beta (IFNb)-1a or glatiramer acetate, whereas two other studies (Rinaldi et al., 2012; Sempere et al., 2013) reported increased severe relapses in patients switching to fingolimod during the 3–4 months after natalizumab discontinuation. Two more recent and larger observational studies (Cohen et al., 2014; Jokubaitis et al., 2014) provided results in favour of disease activity stabilization in patients with an early switch to fingolimod after natalizumab. "
ABSTRACT: OBJECTIVES: to evaluate the effect of age, sex and onset symptoms on the risk of the second clinical attack in a cohort of pediatric patients with a clinically isolated syndrome suggestive of MS (pCIS). BACKGROUND: Pediatric onset occurs in 5-10[percnt] of Multiple Sclerosis (MS) patients. Due to its rare incidence limited epidemiological data are available. METHODS: Demographic and clinical data of a cohort of patients with pCIS and onset <= 15 years were extracted from the Italian iMedWeb registry and from the MSBase platform. A Cox-model adjusted for age at onset, sex and onset symptom(s) was performed to evaluate the time to a second clinical attack during the follow-up. Proportions of patients with different onset symptom(s) (optic, spinal, supratentorial, brainstem/cerebellum and multifocal) were calculated and compared between children (age at onset < 12 years) and adolescents (age at onset > 12) (chi-square test). RESULTS: a total of 1357 of pCIS patients with onset before 15 years was extracted. A shorter time to a second clinical attack was found in female pCIS (male vs female: HR= 0.82; p< 0.02) and in pCIS with an age at onset > 12 years (HR = 1.32; 95[percnt] CI: 1.13-1.54; p=0.0006). Brainstem onset was found to be more frequent in pCIS with an age at onset < 12 years in comparison to pCIS with an age at onset > 12 years (35.93 vs 26.43[percnt]; p=0.0019). CONCLUSIONS: the results indicate that the most significant factors influencing the time to reach a clinically definite MS diagnosis in pCIS are the female sex and an age at onset > 12 years. Moreover the results confirm that brainstem symptoms at onset are more frequent in children than in adolescents.
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