scholarly journals Disease Reactivation after Fingolimod Discontinuation in Pregnant Multiple Sclerosis Patients

2021 ◽  
Author(s):  
Assunta Bianco ◽  
Matteo Lucchini ◽  
Rocco Totaro ◽  
Roberta Fantozzi ◽  
Giovanna De Luca ◽  
...  
Keyword(s):  
Brain Magnetic Resonance Imaging ◽  
First Year ◽  
Resonance Imaging ◽  
Foetal Development ◽  
Specific Data ◽  
Disease Modifying Drugs ◽  
T2 Lesions ◽  
Unplanned Pregnancies ◽  
Disease Reactivation ◽  
Multiple Sclerosis Patients

AbstractRecent studies estimated an incidence of 4–25% of disease rebound after withdrawal of fingolimod (FTY) for any reason, but specific data on disease reactivation after FTY withdrawal due to pregnancy are limited. The aim of the study was to evaluate the frequency and predictors of disease reactivation in patients who stopped FTY for pregnancy. A multicentre retrospective cohort study was conducted in four Italian MS centres in 2013–2019. Both planned and unplanned pregnancies were included. The annualized relapse rate (ARR) was calculated before FTY treatment, during FTY treatment, during pregnancy and during the year after delivery. In total, 27 patients (mean age 29 years) were included. The ARR 1 year before FTY treatment was 1.3. Patients were exposed to FTY for a median of 2.9 years. The ARR was 0.04 during the last year before conception (p < 0.001 compared with the ARR before FTY treatment). Eleven patients became pregnant after a mean of 88 days following FTY discontinuation, whereas 16 patients stopped FTY after pregnancy confirmation. Relapses were observed in 22% of patients during pregnancy and in 44% in the postpartum period. ARR increased both during pregnancy (0.49; p = 0.027) and in the first year after delivery (0.67; p < 0.001) compared to the last year before pregnancy. Compared with radiological assessment before pregnancy, more patients showed new or enlarging T2 lesions (63% vs 30%; p = 0.02) and gadolinium-enhancing lesions (44% vs 0; p = 0.0001) on brain Magnetic Resonance Imaging. Relapses during pregnancy were the only significant predictor for postpartum relapses (OR 1.9, 95% CI 1.11–3.1). One case of spontaneous abortion and no cases of abnormal foetal development were observed. Despite adequate and prolonged control of disease activity, women who discontinue FTY because of pregnancy are at risk for disease reactivation. In patients who relapsed during pregnancy, the initiation of high-efficacy disease modifying drugs (DMDs) soon after delivery is advisable to prevent postpartum relapses.

scholarly journals Reducing return of disease activity in patients with relapsing multiple sclerosis transitioned from natalizumab to teriflunomide: 12-month interim results of teriflunomide therapy

2019 ◽  
Vol 5 (1) ◽  
pp. 205521731882461
Author(s):  
Stanley L Cohan ◽  
Keith Edwards ◽  
Lindsay Lucas ◽  
Tiffany Gervasi-Follmar ◽  
Judy O’Connor ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Brain Magnetic Resonance Imaging ◽  
T2 Lesions ◽  
Disability Status ◽  
The Mean ◽  
Multiple Sclerosis Patients ◽  
Mean Time ◽  
Relapsing Multiple Sclerosis

Background Natalizumab is an effective treatment for relapsing multiple sclerosis. Return of disease activity upon natalizumab discontinuance creates the need for follow-up therapeutic strategies. Objective To assess the efficacy of teriflunomide following natalizumab discontinuance in relapsing multiple sclerosis patients. Methods Clinically stable relapsing multiple sclerosis patients completing 12 or more consecutive months of natalizumab, testing positive for anti-John Cunningham virus antibody, started teriflunomide 14 mg/day, 28 ± 7 days after their final natalizumab infusion. Physical examination, Expanded Disability Status Scale, laboratory assessments, and brain magnetic resonance imaging were performed at screening and multiple follow-up visits. Results Fifty-five patients were enrolled in the study. The proportion of patients relapse-free was 0.94, restricted mean time to first gadolinium-enhancing lesion was 10.9 months and time to 3-month sustained disability worsening was 11.8 months. The mean number of new or enlarging T2 lesions per patient at 12 months was 0.42. Exploratory analyses revealed an annualized relapse rate of 0.08, and a proportion of patients with no evidence of disease activity of 0.68. Forty-seven patients (85.5%) reported adverse events, 95% of which were mild to moderate. Conclusions Teriflunomide therapy initiated without natalizumab washout resulted in a low rate of return of disease activity. Clinicians may consider this a worthwhile strategy when transitioning clinically stable patients off natalizumab to another therapy. ClinicalTrials.gov Identifier: NCT01970410

Alterations in serum MMP-8, MMP-9, IL-12p40 and IL-23 in multiple sclerosis patients treated with interferon-β1b

2010 ◽  
Vol 16 (7) ◽  
pp. 801-809 ◽  
Author(s):  
JS Alexander ◽  
MK Harris ◽  
SR Wells ◽  
G. Mills ◽  
K. Chalamidas ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Magnetic Resonance Imaging ◽  
First Year ◽  
Serial Measurement ◽  
Blood Brain Barrier Disruption ◽  
Matrix Metalloproteinase 1 ◽  
Relapsing Remitting ◽  
Th17 Cytokines ◽  
Brain Barrier Disruption ◽  
Multiple Sclerosis Patients

Background: Interferon-β1b (IFN-β1b), an effective treatment for multiple sclerosis (MS), lessens disease severity in MS patients. However, the mechanisms of its immunoregulatory and anti-inflammatory effects in MS remain only partially understood. Matrix metalloproteinases (MMP) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) are involved in blood brain barrier disruption and formation of MS lesions. Th1/Th17 cytokines e.g. interleukins IL-12p40, IL-17, and IL-23, are associated with MS disease activity and are significant players in pathogenesis of MS. Objective: During a 1-year prospective study, we serially measured serum MMP-8, MMP-9, TIMP-1, IL-12p40, IL-17, and IL-23 in 24 patients with relapsing—remitting MS. We compared the results to clinical course and to brain magnetic resonance imaging. IFN-β1b decreased serum MMP-8 and MMP-9 (not TIMP-1). Results: The sustained treatment with IFN-β1b attenuated the pro-inflammatory environment by significantly reducing the serum IL-12p40, IL-23, and showed a trend for decreasing IL-17. Decreased serum MMP-8, MMP-9, IL-12 and IL-23 levels were correlated with a decrease in the number of contrast-enhanced T2-weighted lesions. Conclusion: Early treatment of MS with IFN-β1b may stabilize clinical disease by attenuating levels of inflammatory cytokines and MMPs. Serial measurement of inflammatory mediators may serve as sensitive markers to gauge therapeutic responses to IFN-β1b during the first year of treatment.

Interferon beta failure predicted by EMA criteria or isolated MRI activity in multiple sclerosis

2013 ◽  
Vol 20 (5) ◽  
pp. 566-576 ◽  
Author(s):  
Luca Prosperini ◽  
Chiara Rosa Mancinelli ◽  
Laura De Giglio ◽  
Floriana De Angelis ◽  
Valeria Barletta ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Interferon Beta ◽  
European Medicines Agency ◽  
First Year ◽  
Resonance Imaging ◽  
T2 Lesions ◽  
Increased Risk ◽  
Magnetic Resonance Imaging Mri ◽  
One Year

Objective: The objective of this paper is to investigate four-year outcomes of interferon beta (IFNB)-treated patients with multiple sclerosis (MS) according to their clinical or magnetic resonance imaging (MRI) activity status at first year of treatment. Methods: A total of 370 patients with MS duration ≤5 years before IFNB start were followed-up for four years. The optimal threshold for one-year MRI activity that more accurately predicted subsequent relapses or disability worsening was identified. The risk of relapses and disability worsening after the first year was then estimated by propensity score (PS)-adjusted analyses in patients fulfilling European Medicines Agency (EMA) criteria for second-line escalation and in those with isolated MRI activity. Results: A total of 192 (51.9%) patients relapsed, and 66 (17.8%) worsened in disability from year 1 to 4 of follow-up. The more accurate threshold for one-year MRI activity was the occurrence of ≥1 enhancing or ≥2 new T2-lesions. An increased risk of relapses and disability worsening was found in either patients fulfilling EMA criteria (hazard ratio (HR) = 3.69, and HR = 6.02) and in those experiencing isolated MRI activity (HR = 3.15, and HR = 5.31) at first year of treatment, when compared with stable patients (all p values <0.001). Conclusion: The four-year outcomes of patients with isolated MRI activity did not differ from those fulfilling EMA criteria at first year of IFNB treatment.

scholarly journals Slowly expanding/evolving lesions as a magnetic resonance imaging marker of chronic active multiple sclerosis lesions

2018 ◽  
Vol 25 (14) ◽  
pp. 1915-1925 ◽  
Author(s):  
Colm Elliott ◽  
Jerry S Wolinsky ◽  
Stephen L Hauser ◽  
Ludwig Kappos ◽  
Frederik Barkhof ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Brain Mri ◽  
Brain Magnetic Resonance Imaging ◽  
Tissue Loss ◽  
Jacobian Determinant ◽  
Resonance Imaging ◽  
T2 Lesions ◽  
Magnetic Resonance Imaging Mri

Background: Chronic lesion activity driven by smoldering inflammation is a pathological hallmark of progressive forms of multiple sclerosis (MS). Objective: To develop a method for automatic detection of slowly expanding/evolving lesions (SELs) on conventional brain magnetic resonance imaging (MRI) and characterize such SELs in primary progressive MS (PPMS) and relapsing MS (RMS) populations. Methods: We defined SELs as contiguous regions of existing T2 lesions showing local expansion assessed by the Jacobian determinant of the deformation between reference and follow-up scans. SEL candidates were assigned a heuristic score based on concentricity and constancy of change in T2- and T1-weighted MRIs. SELs were examined in 1334 RMS patients and 555 PPMS patients. Results: Compared with RMS patients, PPMS patients had higher numbers of SELs ( p = 0.002) and higher T2 volumes of SELs ( p < 0.001). SELs were devoid of gadolinium enhancement. Compared with areas of T2 lesions not classified as SEL, SELs had significantly lower T1 intensity at baseline and larger decrease in T1 intensity over time. Conclusion: We suggest that SELs reflect chronic tissue loss in the absence of ongoing acute inflammation. SELs may represent a conventional brain MRI correlate of chronic active MS lesions and a candidate biomarker for smoldering inflammation in MS.

Switching therapy from natalizumab to fingolimod in relapsing–remitting multiple sclerosis: clinical and magnetic resonance imaging findings

2012 ◽  
Vol 18 (11) ◽  
pp. 1640-1643 ◽  
Author(s):  
F Rinaldi ◽  
D Seppi ◽  
M Calabrese ◽  
P Perini ◽  
P Gallo
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Jc Virus ◽  
Therapeutic Option ◽  
Brain Magnetic Resonance Imaging ◽  
Clinical Activity ◽  
Resonance Imaging ◽  
Relapsing Remitting ◽  
Disease Reactivation

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.

scholarly journals MOG-IgG associated optic neuritis is not multiple sclerosis

2017 ◽  
Vol 75 (10) ◽  
pp. 687-691 ◽  
Author(s):  
Bruna Klein da Costa ◽  
Giordani Rodrigues dos Passos ◽  
Jefferson Becker ◽  
Douglas Kazutoshi Sato
Keyword(s):  
Multiple Sclerosis ◽  
Optic Neuritis ◽  
Brain Magnetic Resonance Imaging ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Resonance Imaging ◽  
Male Ratio ◽  
T2 Lesions ◽  
Central Nervous System Disorders ◽  
A Cell ◽  
The Brain

ABSTRACT Autoantibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have been reported in patients with inflammatory central nervous system disorders including isolated optic neuritis (ON). We compared our MOG-IgG ON patients with multiple sclerosis (MS) patients presenting with ON. Methods and results: Among the total of 38 patients with optic neuropathies, six patients with isolated ON were MOG-IgG positive and eight patients with ON fulfilled the diagnostic criteria for MS. All MS patients were negative for MOG-IgG using a cell-based assay. When compared with the MS group, the MOG-IgG patients were older (mean 47 years), more frequently male (ratio 2:1) and had a higher frequency of bilateral and/or recurrent ON. The brain magnetic resonance imaging of all MOG-IgG positive patients was normal or had only unspecific white matter T2 lesions. Conclusion: These findings suggest that MOG-IgG is a biomarker of an inflammatory demyelinating CNS disease distinct from MS.

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