Factors associated with fingolimod rebound: A single center real-life experience

Göncüoğlu, Cansu; Tuncer, Aslı; Bayraktar-Ekincioglu, Aygin; Cagan, Cansu Ayvacioglu; Acar-Ozen, Pinar; Çakan, Melike; Karabulut, Erdem; Karabudak, Rana

doi:10.1016/j.msard.2021.103278

Cited by 15 publications

(10 citation statements)

References 26 publications

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“…About one-third of our patients did not receive a subsequent DMT within 6 months after fingolimod discontinuation. Long wash-out (>4–8 weeks) is a risk factor for relapses following discontinuation of natalizumab15 and fingolimod 9 16. Severe rebound disease, sometimes resembling immune reconstitution syndrome, has been described as early as 3 weeks following fingolimod discontinuation9 17 18 including one fatal case 19…”

Section: Discussionmentioning

confidence: 99%

Rebound of clinical disease activity after fingolimod discontinuation? A nationwide cohort study of patients in Denmark

Framke

Pontieri²,

Bramow³

et al. 2022

J Neurol Neurosurg Psychiatry

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ObjectiveWe investigated whether clinical rebound occurred after fingolimod discontinuation in a complete population of patients with relapsing-remitting multiple sclerosis (RRMS) in Denmark. We further identified clinical and demographical factors associated with disease reactivation after fingolimod discontinuation.MethodsThe population comprised 992 RRMS patients treated with fingolimod for 6 months or more. We estimated annualised relapse rates (ARR) before, during and after treatment. We estimated overall ARRs and ARRs stratified by disease activity before discontinuation. We calculated the proportion of patients with a higher clinical disease activity after discontinuation than before treatment start. Finally, we analysed the association between variables at discontinuation and time to first relapse after discontinuation.ResultsThe ARR 3 months after discontinuation (ARR=0.56; 95% CI=0.47 to 0.66) was statistically significantly lower (p<0.01) than the ARR 1 year before treatment (ARR=0.74; 95% CI=0.69 to 0.80). Results were similar when repeating analyses in patients with and without disease activity before discontinuation. In total, 124 patients (12.5%) had clinical rebound. Of those, 36 had no disease breakthrough before discontinuation (3.6% of total population). On treatment disease activity (HR=1.98, p<0.01), lower age (HR=0.98, p=0.01) and female sex (HR=1.68, p=0.02) were associated with a higher relapse risk after discontinuation.ConclusionsBased on average ARR levels, there was no evidence of clinical rebound after fingolimod discontinuation. In total, 12.5% of patients had clinical rebound. Only 3.6%, however, had clinical rebound without disease activity before discontinuation. Disease activity before discontinuation, female sex and younger age were statistically significantly associated with a higher relapse risk after discontinuation.

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Section: Discussionmentioning

confidence: 99%

Rebound of clinical disease activity after fingolimod discontinuation? A nationwide cohort study of patients in Denmark

Framke

Pontieri²,

Bramow³

et al. 2022

J Neurol Neurosurg Psychiatry

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“…Moreover, the need for phosphorylation in other to act on the CNS S1PR 5 , which might be decreased within the CNS of people with more advanced disease, could explain its failure to prove efficacy in delaying disability progression in people with PPMS. More real-life data is needed to clarify if and what are the factors which are associated with rebound post-fingolimod, which were suggested by some [ 102 ] but not confirmed by others [ 103 ]. Siponimod is the only S1PR modulator to prove clinically significant efficacy in people with active SPMS, by reducing confirmed disability progression unrelated to relapses or magnetic resonance imaging activity, as well as the time until the need to use a wheelchair.…”

Section: Expert Opinionmentioning

confidence: 99%

An update on the use of sphingosine 1-phosphate receptor modulators for the treatment of relapsing multiple sclerosis

Dumitrescu

Παπαθανασίου

Coclitu

et al. 2023

Expert Opinion on Pharmacotherapy

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Introduction Multiple sclerosis (MS) is an immune-mediated disorder of the CNS manifested by recurrent attacks of neurological symptoms (related to focal inflammation) and gradual disability accrual (related to progressive neurodegeneration and neuroinflammation). Sphingosine-1-phosphate-receptor (S1PR) modulators are a class of oral disease-modifying therapies (DMTs) for relapsing MS. The first S1PR modulator developed and approved for MS was fingolimod, followed by siponimod, ozanimod, and ponesimod. All are S1P analogues with different S1PR-subtype selectivity. They restrain the S1P-dependent lymphocyte egress from lymph nodes by binding the lymphocytic S1P-subtype-1-receptor. Depending on their pharmacodynamics and pharmacokinetics, they can also interfere with other biological functions. Areas covered Our narrative review covers the PubMed English literature on S1PR modulators in MS until August 2022. We discuss their pharmacology, efficacy, safety profile, and risk management recommendations based on the results of phase II and III clinical trials. We briefly address their impact on the risk of infections and vaccines efficacy. Expert opinion S1PR modulators decrease relapse rate and may modestly delay disease progression in people with relapsing MS. Aside their established benefit, their place and timing within the long-term DMT strategy in MS, as well as their immunological effects in the new and evolving context of the post-COVID-19 pandemic and vaccination campaigns warrant further study.

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“…Despite the observations upon treatment cessation described above, no well-controlled data have yet shown a consistent increase of disease activity, or rebound activity, following discontinuation of anti-CD20 therapies or most HETs [37,41,42,74,75]. Rebound activity has been reported following discontinuation of sequestering therapies, such as fingolimod [98][99][100] and natalizumab [101][102][103]. However, rapid switch to an anti-CD20 treatment, such as ocrelizumab, may reduce this rebound risk [104].…”

Section: Hematologic Abnormalitiesmentioning

confidence: 99%

High-Efficacy Therapies for Treatment-Naïve Individuals with Relapsing–Remitting Multiple Sclerosis

et al. 2022

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There are > 18 distinct disease-modifying therapy (DMT) options covering 10 mechanisms of action currently approved by the US Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis (RRMS). Given the multitude of available treatment options, and recent international consensus guidelines offering differing recommendations, there is broad heterogeneity in how the DMTs are used in clinical practice. Choosing a DMT for newly diagnosed patients with MS is currently a topic of significant debate in MS care. Historically, an escalation approach to DMT was used for newly diagnosed patients with RRMS. However, the evidence for clinical benefits of early treatment with high-efficacy therapies (HETs) in this population is emerging. In this review, we provide an overview of the DMT options and MS treatment strategies, and discuss the clinical benefits of HETs (including ofatumumab, ocrelizumab, natalizumab, alemtuzumab, and cladribine) in the early stages of MS, along with safety concerns associated with these DMTs. By minimizing the accumulation of neurological damage early in the disease course, early treatment with HETs may enhance long-term clinical outcomes over the lifetime of the patient.

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Factors associated with fingolimod rebound: A single center real-life experience

Cited by 15 publications

References 26 publications

Rebound of clinical disease activity after fingolimod discontinuation? A nationwide cohort study of patients in Denmark

Rebound of clinical disease activity after fingolimod discontinuation? A nationwide cohort study of patients in Denmark

An update on the use of sphingosine 1-phosphate receptor modulators for the treatment of relapsing multiple sclerosis

High-Efficacy Therapies for Treatment-Naïve Individuals with Relapsing–Remitting Multiple Sclerosis

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