Severe disease reactivation in four patients with relapsing–remitting multiple sclerosis after fingolimod cessation

Berger, Benjamin; Baumgartner, Annette; Rauer, Sebastian; Mader, Irina; Luetzen, Niklas; Farenkopf, Ulrich; Stich, Oliver

doi:10.1016/j.jneuroim.2015.03.022

Cited by 67 publications

(61 citation statements)

References 19 publications

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“…In accordance with this, several case reports have described rebound events approximately 2–4 months after stopping FTY 43, 44, 45, 47, 50, 51, 53, 55. Overexpression of sphingosine‐1‐phosphate receptors in entrapped lymphocytes and massive egress of lymphocytes after FTY cessation, observed in animal models, seem to be plausible explanations for such an aggressive disease reactivation in some patients 2.…”

Section: Rebound After Withdrawal Of Fingolimodsupporting

confidence: 67%

“…Similarly, there are some case reports of exacerbation after discontinuation of FTY 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56. Patients with highly active disease before the start of treatment with FTY51 or who showed a good therapeutic response to FTY53 might be predisposed to severe rebound after withdrawal. A case of severe rebound of spinal cord MS activity after FTY withdrawal was also reported 49…”

Section: Rebound After Withdrawal Of Fingolimodmentioning

confidence: 97%

“…Berger et al reported that partial recovery was achieved after steroid pulse therapy followed by PLEX 51. However, most of the cases did not immediately respond to steroid 54.…”

Section: Rebound After Withdrawal Of Fingolimodmentioning

confidence: 99%

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Neurological safety of fingolimod: An updated review

Yoshii

Moriya

Ohnuki

et al. 2017

Clinical & Exp Neuroim

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Fingolimod (FTY) is the first oral medication approved for treatment of relapsing–remitting multiple sclerosis (RRMS). Its effectiveness and safety were confirmed in several phase III clinical trials, but proper evaluation of safety in the real patient population requires long‐term post‐marketing monitoring. Since the approval of FTY for RRMS in Japan in 2011, it has been administered to approximately 5000 MS patients, and there have been side‐effect reports from 1750 patients. Major events included infectious diseases, hepatobiliary disorders, nervous system disorders and cardiac disorders. In the present review, we focus especially on central nervous system adverse events. The topics covered are: (i) clinical utility of FTY; (ii) safety profile; (iii) post‐marketing adverse events in Japan; (iv) white matter (tumefactive) lesions; (v) rebound after FTY withdrawal; (vi) relationship between FTY and progressive multifocal leukoencephalopathy; (vii) FTY and progressive multifocal leukoencephalopathy‐related immune reconstitution inflammatory syndrome; and (viii) neuromyelitis optica and leukoencephalopathy.

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Section: Rebound After Withdrawal Of Fingolimodsupporting

confidence: 67%

Section: Rebound After Withdrawal Of Fingolimodmentioning

confidence: 97%

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Neurological safety of fingolimod: An updated review

Yoshii

Moriya

Ohnuki

et al. 2017

Clinical & Exp Neuroim

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“…Fingolimod rebound syndrome has been reported in a growing number of case series, [3][4][5][6][7][8][9][10][11][12][13][14][15][16] and there were three case series composed of a relatively large number of patients. 3,15,16 In the three studies, the prevalence of fingolimod rebound syndrome ranged from 5 to 53%, although the study whose prevalence was 53% included radiological exacerbation.…”

Section: Discussionmentioning

confidence: 99%

Debate on the treatment of multiple sclerosis: Experience from an intractable multiple sclerosis case with rebound syndrome after fingolimod cessation

Kuroda

Nishiyama

Matsumoto

et al. 2019

Clinical & Exp Neuroim

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Background Fingolimod is an effective disease-modifying drug for relapsing-remitting multiple sclerosis (RRMS), but drug discontinuation might cause rebound syndrome, defined as massive and prolonged exacerbation of MS. We report a case of intractable MS with rebound syndrome after fingolimod cessation. Case presentation A 54-year-old patient with RRMS had been disease activity-free for 9 years during fingolimod treatment. However, she discontinued fingolimod by her own decision out of concern for progressive multifocal leukoencephalopathy. Five weeks after drug cessation, she developed progressive weakness in the left leg. Expanded Disability Status Scale scores worsened from 2.0 to 6.0. Blood tests showed recovery of lymphocyte count (1000/mm 3 ) from the previous counts. Cerebrospinal fluid examination showed almost normal results, except for marked elevation of myelin basic protein (1420 pg/mL). Brain magnetic resonance imaging showed a massive lesion in the right frontal lobe with open-ring enhancement and a small enhancing lesion in the left parietal lobe. Based on diagnosis as exacerbation of RRMS, the patient was treated with intravenous methylprednisolone, followed by oral dimethyl fumarate. However, 5-month use of DMF could not remit the disease activity, leading to fingolimod reinitiation. Conclusions Rebound syndrome is an intractable complication of exit strategy for fingolimod-treated RRMS patients. To lower the risk for rebound syndrome, specific mechanisms of rebound syndrome are to be clarified. Furthermore, concise risk stratification for progressive multifocal leukoencephalopathy in fingolimod treatment is imperative. Taken together, the risk-benefit analysis for fingolimod treatment, including rebound syndrome as well as progressive multifocal leukoencephalopathy, is required to initiate the drug.

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“…In Europe, its use is indicated for aggressive forms of relapsingremitting MS. Data from clinical trials showed that annualized relapse rates (ARRs) were more than 50% lower in subjects taking oral fingolimod compared to subjects taking placebo [1,2]. Since 2012, several reports have described a 'rebound syndrome' after fingolimod discontinuation [3][4][5][6][7][8][9][10][11][12][13][14]. There is no shared definition of 'clinical rebound syndrome'; the most widely used definition is 'a disease reactivation which surpasses the pretreatment activity level', especially with regard to ARR [15,16].…”

Section: Introductionmentioning

confidence: 99%