Abnormal inflammatory activity returns after natalizumab cessation in multiple sclerosis

Guéguen, Antoine; Roux, P. Le; Deschamps, Romain; Moulignier, Antoine; Bensa, Caroline; Savatovsky, Julien; Héran, F.; Gout, Olivier

doi:10.1136/jnnp-2014-307591

Cited by 43 publications

(51 citation statements)

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“…Across 11 studies, 2 reported no evidence of rebound 123,135 and 1 reported no evidence of immune reconstitution inflammatory syndrome. 128 The proportion of participants showing evidence of rebound ranged, in most of the studies, from 9% to 12%, 126,127,131,132,137 whereas other authors reported higher rebounds, including 14%, 136 21.2% 134 and 38.3%. 138 Relapse outcomes.…”

Section: Review Questionmentioning

confidence: 98%

“…After a full-text review and removal of duplicates, 19 studies met the eligibility criteria for this review. One study was an RCT; 120 12 were prospective cohort studies; [121][122][123][124][125][126][127][128][129][130][131][132] and six were retrospective cohorts. [133][134][135][136] In 15 studies, participants were receiving natalizumab before discontinuing treatment due to safety issues, whereas in one study, 127 participants were receiving fingolimod.…”

Section: Review Questionmentioning

confidence: 99%

“…121 Various studies reported an increase in the mean number of GAD lesions in all participants as a group during the pre-natalizumab period compared to that during the post-natalizumab period. 126,128,131,138 Quality assessment. The study quality was assessed with the 'Quality Assessment of Before-After (PrePost) Studies With No Control Group' tool developed by the National Heart, Lung, and Blood Institute and the Research Triangle Institute International.…”

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confidence: 99%

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ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

et al. 2018

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Background and scopeMultiple sclerosis (MS) is an inflammatory-demyelinating disease of the central nervous system (CNS) that is characterized by inflammation, demyelination and degenerative changes. MS usually begins around the age between 20 and 40 years and affects two to three times as many women as men; it also constitutes the most frequent cause of non-traumatic disability in the young adult population. 1 The incidence of MS varies across regions, with rates as high as 8 to 10 new cases per 100,000 in high latitudinal regions. 2,3 Current estimates suggest that over 700,000 people are affected in Europe, with over 2.5 million cases worldwide, 4 which represent a significant burden in terms of impact on quality of life, societal costs and personal expenses. 5,6 Most patients (85%-90%) have a relapsing course from onset that is characterized by relapses and remissions of neurological symptoms Methods: This guideline has been developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology and following the updated EAN recommendations. Clinical questions were formulated in Patients-Intervention-Comparator-Outcome (PICO) format and outcomes were prioritized. The quality of evidence was rated into four categories according to the risk of bias. The recommendations with assigned strength (strong and weak) were formulated based on the quality of evidence and the risk-benefit balance. Consensus between the panelists was reached by use of the modified nominal group technique. Results: A total of 10 questions were agreed, encompassing treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and treatment strategies in MS and pregnancy. The guideline takes into account all disease-modifying drugs approved by the European Medicine Agency (EMA) at the time of publication. A total of 21 recommendations were agreed by the guideline working group after three rounds of consensus. Conclusion:The present guideline will enable homogeneity of treatment decisions across Europe. associated with areas of CNS inflammation, and over the course of two decades, more than half of untreated patients transition to a phase of gradual worsening independent of acute attacks. 7,8 Progressive forms of MS can be present as the initial disease course (primary-progressive MS) in approximately 10%-15% of patients. 9,10 There is no curative treatment available for MS, and the current therapeutic strategy is aimed at reducing the risk of relapses and potentially disability progression. The treatment era for MS began in 1993, when the first interferon became available, and recent years have seen a large expansion in the therapeutic options for MS, with 11 disease-modifying therapies (DMTs) approved by the European Medicine Agency (EMA) in both injectable and oral formulations by the beginning of 2017. 11 The growing armamentarium of therapies brings new opportunities for individualized therapy where patients and providers must balance considerations around efficacy,...

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Section: Review Questionmentioning

confidence: 98%

Section: Review Questionmentioning

confidence: 99%

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confidence: 99%

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ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

et al. 2018

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“…Stüve et al 17 reported on a small group of patients (n = 23) followed with immunologic, clinical, and MRI evaluations during 14 months after discontinuation of NZ that the effect of NZ decreased over a 3- to 6-month period. Similarly, a North American study 18 based on 175 patients with MS treated with NZ for at least 1 year showed that gadolinium-enhancing lesions were first detected 3 months after the last NZ infusion, and authors 19 reported in a small group of patients (n = 32) a reactivation of disease activity between 3 and 9 months after NZ interruption, independently of an alternative treatment prescribed.…”

Section: Discussionmentioning

confidence: 95%

Risk of relapse after natalizumab withdrawal

Papeix

Vukusic

Casey

et al. 2016

Neurol Neuroimmunol Neuroinflamm

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Objective:To assess disease activity within 12 months after natalizumab (NZ) discontinuation in a large French postmarketing cohort.Methods:In France, patients exposed at least once to NZ were included in the TYSEDMUS observational and multicenter cohort, part of the French NZ Risk Management Plan. Clinical disease activity during the year following NZ discontinuation was assessed in this cohort. Time to first relapse after NZ stop was analyzed using Kaplan-Meier method and potentially associated factors were studied using a multivariate Cox model.Results:Out of the 4,055 patients with multiple sclerosis (MS) included in TYSEDMUS, 1,253 discontinued NZ and 715 of them had relevant data for our study. The probability of relapse within the year after NZ stop was estimated at 45% (95% confidence interval 0.41–0.49).Conclusions:This large and systematic survey of patients with MS after NZ withdrawal allows quantifying the risk of increased disease activity following treatment discontinuation. This study provides large-scale, multicenter, systematic data after NZ cessation in real-life settings.

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“…Due to the PML risk, natalizumab is often discontinued leading to MS disease reactivation [5] however, the ideal alternative treatment following natalizumab has not yet been identified [6][7][8]. Fingolimod (Gilenya, Novartis, Basel, Switzerland) is an option for these patients [1,3,[8][9][10][11][12] however, because of the still unknown impact on the immune system of the concomitant presence of these molecules, an interval is recommended between discontinuing natalizumab and starting fingolimod.…”

Section: Introductionmentioning

confidence: 99%

Natalizumab to Fingolimod Switching in Multiple Sclerosis: Results from a Â“Real WordÂ” Retrospective Analysis

Rasia¹,

Cordioli²,

Rossi³

et al. 2015

J Mult Scler

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JMSO, an open access journal Rasia et al., J Mult Scler (Foster City) AbstractFingolimod is an alternative for patients with multiple sclerosis who discontinue natalizumab because of leukoencephalopathy risk. However, the interruption of natalizumab might cause disease reactivation. We aimed to describe the disease course of patients switching to fingolimod after treatment with natalizumab or β-interferon, in a real-world setting, through a retrospective analysis of data in patients with multiple sclerosis that receiving fingolimod at a single centre in Italy. Ninety patients were divided into two groups: patients switching to fingolimod from natalizumab (n = 43, Group 1), and treatment naïve (n=5) plus patients switching from β-interferon (n = 42) (Group 2). In Group 1, the mean annualised relapse rate significantly increased from 0.36 at natalizumab discontinuation to 0.80 after natalizumab washout and 1.12 after the first 3 months of fingolimod, decreasing thereafter to 0.49 by the end of followup. In Group 2, the relapse rate significantly decreased from 1.16 to 0.47 at the end of follow-up. Relapses during natalizumab washout predicted increased disease activity during the first 3 months of fingolimod (p = 0.043). We conclude that fingolimod has a delayed effect in patients switching from natalizumab versus treatment-naïve patients or those switching from β-interferon. Worsening of disease activity during the washout period may be predictive of treatment failure.

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Abnormal inflammatory activity returns after natalizumab cessation in multiple sclerosis

Abstract: This study identifies rebound after NTZ cessation as an association of relapses and high MRI activity.

Cited by 43 publications

References 10 publications

ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

Risk of relapse after natalizumab withdrawal

Natalizumab to Fingolimod Switching in Multiple Sclerosis: Results from a Â“Real WordÂ” Retrospective Analysis

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