Disease reactivation following fingolimod withdrawal in multiple sclerosis: Two case reports

Forci, Benedetta; Mariottini, Alice; Mechi, Claudia; Massacesi, Luca; Repice, Anna Maria

doi:10.1016/j.msard.2017.05.003

Cited by 16 publications

(14 citation statements)

References 4 publications

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“…The patients in this group had many new or enlarged T2-weighted lesions with Gd enhancement and experienced greater clinical activity than before fingolimod initiation. In previous reports, most brain MR images of MS patients with an increased disease activity after fingolimod cessation showed multiple enhanced lesions, with a disease activity exceeding that observed prior to treatment with fingolimod ( 4 , 5 , 7 , 8 , 11 , 12 , 14 , 16 , 18 , 19 ). These MRI findings from earlier studies may be similar to the pattern observed in the group II cases in our study.…”

Section: Discussionmentioning

confidence: 87%

Disease Exacerbation after the Cessation of Fingolimod Treatment in Japanese Patients with Multiple Sclerosis

et al. 2018

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Objective In Japan, following the launch of dimethyl fumarate (DMF) after fingolimod as a disease-modifying drug in multiple sclerosis (MS), some patients switched from fingolimod to DMF. The aim of this study was to determine the follow-up status of MS patients who switched to DMF after fingolimod cessation. Methods Clinical and magnetic resonance imaging (MRI) data in 19 patients with MS who switched to DMF were collected for at least for 6 months after fingolimod cessation. Results Ten patients (52.6%) experienced clinical or MRI exacerbation after fingolimod cessation. The peripheral blood lymphocyte counts at the time of fingolimod cessation in those with disease exacerbation were significantly lower than in those without exacerbation. The patients with disease exacerbation were further classified into three groups based on MRI findings: those with some new T2-weighted lesions with or without gadolinium (Gd) enhancement (group I), those with more new and/or enlarged T2-weighted lesions with Gd enhancement compared to pre-fingolimod induction (group II), and those with multifocal tumefactive demyelinating lesions. In group II, the clinical disease activity, which was similar to that at fingolimod initiation in group I, was higher than the clinical disease activity observed before fingolimod initiation. Conversely, group III exhibited unexpected new MRI findings that were not evident before fingolimod initiation. Conclusion Cessation of fingolimod might precipitate rebound or reactivation of clinical disease in patients with MS, and careful follow-up is necessary for patients who discontinue fingolimod.

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Section: Discussionmentioning

confidence: 87%

Disease Exacerbation after the Cessation of Fingolimod Treatment in Japanese Patients with Multiple Sclerosis

et al. 2018

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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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“…It is worth noting that some of the clinical case studies that have described a rebound after fingolimod discontinuation [6][7][8][9]13], including the small cohort that was described by Hatcher et al [18], studied patients in whom fingolimod was discontinued due to a lack of efficacy. Given that these patients did not Figure 1 Representation of the annualized relapse rate (ARR) before, during and after fingolimod in three groups of patients: those without relapses after fingolimod discontinuation, those who experienced reactivation and those who experienced a rebound of the disease.…”

Section: Discussionmentioning

confidence: 99%

Clinical activity after fingolimod cessation: disease reactivation or rebound?

Frau

Sormani

Signori

et al. 2018

Euro J of Neurology

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Disease reactivation following fingolimod withdrawal in multiple sclerosis: Two case reports

Cited by 16 publications

References 4 publications

Disease Exacerbation after the Cessation of Fingolimod Treatment in Japanese Patients with Multiple Sclerosis

Disease Exacerbation after the Cessation of Fingolimod Treatment in Japanese Patients with Multiple Sclerosis

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

Clinical activity after fingolimod cessation: disease reactivation or rebound?

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