Clinical activity after Fingolimod cessation: disease reactivation or rebound?

Frau, Jessica

doi:10.26226/morressier.59a3e8b7d462b8028d895667

Cited by 13 publications

(26 citation statements)

References 16 publications

(21 reference statements)

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“…Notably, 3/8 of these patients had breakthrough disease activity while on fingolimod. In a cohort with stable disease on fingolimod (relapse-free for at least 6 months), baseline ARR was not found to be risk factor for rebound [8]. Nevertheless, it is advisable to be vigilant for severe relapses after stopping treatment in a patient who had breakthrough disease on fingolimod, even if such a situation might not represent true disease rebound.…”

Section: Risk Factors For Reboundmentioning

confidence: 94%

“…They hypothesize that the withdrawal of fingolimod resulted in astrocytic overexpression of S1P1 and a downstream inflammatory response, possibly mediated by NF-jB activation and release of inflammatory cytokines and nitric oxide. Overall, however, when compared to natalizumab, fingolimod rebound is relatively less well characterized [8], and it has been argued that severe relapses after fingolimod cessation constitute expected reactivation of disease rather than true rebound [7].…”

Section: Reports Of Disease Rebound After Fingolimod Discontinuationmentioning

confidence: 99%

“…In one center, 5/46 patients (10.9%) who discontinued fingolimod had a severe relapse within 4 months [42]. Another group analyzed patients who stopped fingolimod after a relapse-free interval of at least 6 months and noted that 10/100 patients had severe disease reactivation [8]. Out of these 10 patients, five were considered to have true rebound, as investigators noted that the relapse activity was more severe than the patients' prefingolimod baseline.…”

Section: Reports Of Disease Rebound After Fingolimod Discontinuationmentioning

confidence: 99%

“…While the lack of available follow-up data in a majority of these patients has been criticized as a weakness [8], this data is the only published comparison of patients who discontinued fingolimod to an untreated, matched patient population. Although the lack of extended follow-up time likely results in overall underestimated severe relapse rates in both placebo and fingolimod discontinuation groups compared to other cohorts (Table 1), availability of patient data at 7 months after study drug discontinuation was the same for placebo and fingolimod groups [46].…”

Section: Reports Of Disease Rebound After Fingolimod Discontinuationmentioning

confidence: 99%

“…Reasons for treatment changes include adverse effects, treatment failure, disease progression, comorbidities, life cycle events such as pregnancy and lactation, and evolving patient preferences. Severe disease reactivation after the withdrawal of DMT that exceeds a patient's pre-DMT baseline is considered a rebound event, although there is no consensus definition of severe disease reactivation [6][7][8]. As fulminant MS rebound events resembling immune reconstitution inflammatory syndrome (IRIS) have been reported with the withdrawal of treatment in MS [9,10], it is important for the clinician to be aware of the circumstances when patients are at risk for severe disease reactivation.…”

Section: Introduction To Rebound In Multiple Sclerosismentioning

confidence: 99%

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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: Risk Factors For Reboundmentioning

confidence: 94%

Section: Reports Of Disease Rebound After Fingolimod Discontinuationmentioning

confidence: 99%

Section: Reports Of Disease Rebound After Fingolimod Discontinuationmentioning

confidence: 99%

Section: Reports Of Disease Rebound After Fingolimod Discontinuationmentioning

confidence: 99%

Section: Introduction To Rebound In Multiple Sclerosismentioning

confidence: 99%

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

et al. 2019

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Abuse and dependence potential of sphingosine-1-phosphate (S1P) receptor modulators used in the treatment of multiple sclerosis: a review of literature and public data

Schoedel¹,

Kolly

Gardin

et al. 2021

Psychopharmacology

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Abuse and misuse of prescription drugs remains an ongoing concern in the USA and worldwide; thus, all centrally active new drugs must be assessed for abuse and dependence potential. Sphingosine-1-phosphate (S1P) receptor modulators are used primarily in the treatment of multiple sclerosis. Among the new S1P receptor modulators, siponimod, ozanimod, and ponesimod have recently been approved in the USA, European Union (EU), and other countries. This review of literature and other public data has been undertaken to assess the potential for abuse of S1P receptor modulators, including ozanimod, siponimod, ponesimod, and fingolimod, as well as several similar compounds in development. The S1P receptor modulators have not shown chemical or pharmacological similarity to known drugs of abuse; have not shown abuse or dependence potential in animal models for subjective effects, reinforcement, or physical dependence; and do not have adverse event profiles demonstrating effects of interest to individuals who abuse drugs (such as sedative, stimulant, mood-elevating, or hallucinogenic effects). In addition, no reports of actual abuse, misuse, or dependence were identified in the scientific literature for fingolimod, which has been on the market since 2010 (USA) and 2011 (EU). Overall, the data suggest that S1P receptor modulators are not associated with significant potential for abuse or dependence, consistent with their unscheduled status in the USA and internationally.

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Preoperative Management of Medications for Neurologic Diseases

Oprea

Keshock

O’Glasser

et al. 2022

Mayo Clinic Proceedings

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Neurologic diseases are prevalent in patients undergoing invasive procedures; yet, no societal guidelines exist as to best practice in management of perioperative medications prescribed to treat these disorders. The Society for Perioperative Assessment and Quality Improvement tasked experts in internal medicine, anesthesiology, perioperative medicine, and neurology to provide evidence-based recommendations for preoperative management of these medications. The aim of this review is not only to provide consensus recommendations for preoperative management of patients on medications for neurologic disorders, but also to serve as an educational guide to perioperative clinicians. While, in general, medications for neurologic disorders should be continued preoperatively, an individualized approach may be needed in certain situations (eg, holding anticonvulsants on day of surgery if electroencephalographic mapping is planned during epilepsy surgery). Pertinent interactions with commonly used drugs in anesthesia practice, as well as considerations for targeted laboratory testing or perioperative drug substitutions, are addressed as well.

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Clinical activity after Fingolimod cessation: disease reactivation or rebound?

Cited by 13 publications

References 16 publications

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

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

Abuse and dependence potential of sphingosine-1-phosphate (S1P) receptor modulators used in the treatment of multiple sclerosis: a review of literature and public data

Preoperative Management of Medications for Neurologic Diseases

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