Rebound of Disease Activity After Withdrawal of Fingolimod (FTY720) Treatment

Havla, Joachim; Pellkofer, Hannah; Meinl, Ingrid; Gerdes, Lisa Ann; Hohlfeld, Reinhard; Kümpfel, Tania

doi:10.1001/archneurol.2011.1057

Cited by 102 publications

(63 citation statements)

References 11 publications

(8 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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%

“…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%

See 1 more Smart Citation

Neurological safety of fingolimod: An updated review

Yoshii

Moriya

Ohnuki

et al. 2017

Clinical & Exp Neuroim

View full text Add to dashboard Cite

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.

show abstract

Section: Rebound After Withdrawal Of Fingolimodsupporting

confidence: 67%

Section: Rebound After Withdrawal Of Fingolimodmentioning

confidence: 99%

Neurological safety of fingolimod: An updated review

Yoshii

Moriya

Ohnuki

et al. 2017

Clinical & Exp Neuroim

View full text Add to dashboard Cite

show abstract

“…The release of lymphocytes after withdrawal of FTY with rapid influx of lymphocytes into the CSF and reconstitution of the immune system has been discussed as reason for MS rebound [Havla et al 2012]. Additionally, whereas B cells in the periphery are strongly reduced they are untouched in the CSF upon treatment with FTY [Kowarik et al 2011].…”

Section: Discussionmentioning

confidence: 99%

Tumefactive multiple sclerosis lesions in two patients after cessation of fingolimod treatment

Faissner

Hoepner

Lukas

et al. 2015

Ther Adv Neurol Disord

View full text Add to dashboard Cite

Background: Fingolimod (FTY) is the first oral medication approved for multiple sclerosis therapy. Until now, little has been known about the effects of FTY withdrawal regarding disease activity and development of tumefactive demyelinating lesions (TDLs), as already described in patients who discontinue natalizumab. Methods: In this study we present the clinical and radiological findings of two patients who had a severe rebound after FTY withdrawal and compare these with patients identified by a PubMed data bank analysis using the search term 'fingolimod rebound'. In total, 10 patients, of whom three developed TDLs, are presented. Results: Patients suffering from TDLs were free of clinical and radiological signs of disease activity under FTY therapy (100% versus 57%, compared with patients without TDLs) and had rebounds after a mean of 14.6 weeks (standard deviation 11.5) [patients without TDLs 11.7 (standard deviation 3.4)]. Conclusion: We propose that a good therapeutic response to FTY might be predisposing for a severe rebound after withdrawal. Consequently, therapy switches should be planned carefully with a short therapy free interval.

show abstract

“…41 After discontinuation of some drugs, there may be a rapid return or even increase in disease activity compared to baseline, a "rebound effect" as reported for natalizumab, [42][43][44] but also in a single case report for fingolimod. 45 It is has not been rigorously proven that there is a rebound following discontinuation of natalizumab, however; the phenomenon may be represent a return to baseline disease activity following natalizumab cessation, similar to the increase in relapse rates observed following pregnancy. 46 47 There are no reports of recurrent disease activity exceeding pre-treatment baseline after discontinuation of interferon, glatiramer acetate or dimethyl-fumarate.…”

Section: Recurrent Disease Activitymentioning

confidence: 99%