Multiple sclerosis rebound after fingolimod discontinuation for lymphopenia

Mantia, L. La; Prone, Valentina; Marazzi, Maria Raffaella; Erminio, Cristina; Protti, Alessandra

doi:10.1007/s10072-014-1800-y

Cited by 26 publications

(22 citation statements)

References 9 publications

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“…Reported cases of unexpected increases in clinical and MRI activity after discontinuation of fingolimod began accumulating in 2012 [10,[25][26][27][28][29][30][31][32][33][34][35], with some including reports of tumefactive lesions on MRI [36][37][38][39][40]. While these cases exhibit a significant amount of clinical heterogeneity, a recently published case series has demonstrated three different MRI patterns of post-fingolimod rebound: tumefactive lesions, a punctated pattern with innumerable small T2 and gadolinium (Gd)enhancing lesions, and a pattern more typical of classical MS [40].…”

Section: Reports Of Disease Rebound After Fingolimod Discontinuationmentioning

confidence: 99%

Fingolimod Rebound: A Review of the Clinical Experience and Management Considerations

et al. 2019

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Because the treatment of multiple sclerosis (MS) may span decades, the need often arises to make changes to the treatment plan in order to accommodate changing circumstances. Switching drugs, or the discontinuation of immunomodulatory agents altogether, may leave patients vulnerable to relapse or disease progression. In some cases, severe MS disease activity is noted clinically and on MRI after treatment withdrawal. When this disease activity is disproportionate to the pattern observed prior to treatment initiation, patients are said to have experienced rebound. Of the US Food and Drug Administration (FDA)-approved agents to treat MS, the drugs most commonly implicated in rebound are natalizumab and fingolimod. In this review based on the reported cases and data from clinical trials, we characterize disease rebound after fingolimod cessation. We also outline fingolimod rebound management considerations, summarizing what evidence is available to help clinicians mitigate the risk of rebound, switch therapies, and treat rebound events when they occur. The commonly encountered situation of fingolimod discontinuation prior to pregnancy is also discussed.

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Section: Reports Of Disease Rebound After Fingolimod Discontinuationmentioning

confidence: 99%

Fingolimod Rebound: A Review of the Clinical Experience and Management Considerations

et al. 2019

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“…An analysis of >1800 patients who stopped NTZ therapy showed that relapse of disease activity was particularly evident in patients who had had highly active disease before NTZ therapy 42. 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.…”

Section: Rebound After Withdrawal Of Fingolimodmentioning

confidence: 99%

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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“…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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Multiple sclerosis rebound after fingolimod discontinuation for lymphopenia

Cited by 26 publications

References 9 publications

Fingolimod Rebound: A Review of the Clinical Experience and Management Considerations

Fingolimod Rebound: A Review of the Clinical Experience and Management Considerations

Neurological safety of fingolimod: An updated review

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

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