Long-term safety and real-world effectiveness of fingolimod in relapsing multiple sclerosis

Druart, Charlotte; Sankari, Souraya El; Pesch, Vincent Van

doi:10.2147/prom.s122401

Cited by 28 publications

(23 citation statements)

References 48 publications

(62 reference statements)

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“…Patients with pre-existing cardiac abnormalities, such as conduction block or ischemic heart disease, or those taking medications that interfere with cardiac rhythm and conduction are advised to have a cardiology consultation if clinically indicated (92). Slight and mostly transient hypertension after initial doses of fingolimod also was observed in the FREEDOMS extension study, however, if it did not resolve, it remained stable over the treatment course (91, 98). Increased frequency of basal-cell carcinoma was reported in patients on long-term fingolimod therapy (91).…”

Section: Fingolimodmentioning

confidence: 84%

Immunological Aspects of Approved MS Therapeutics

et al. 2019

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Multiple sclerosis (MS) is the most common neurological immune-mediated disease leading to disability in young adults. The outcome of the disease is unpredictable, and over time, neurological disabilities accumulate. Interferon beta-1b was the first drug to be approved in the 1990s for relapsing-remitting MS to modulate the course of the disease. Over the past two decades, the treatment landscape has changed tremendously. Currently, more than a dozen drugs representing 1 substances with different mechanisms of action have been approved (interferon beta preparations, glatiramer acetate, fingolimod, siponimod, mitoxantrone, teriflunomide, dimethyl fumarate, cladribine, alemtuzumab, ocrelizumab, and natalizumab). Ocrelizumab was the first medication to be approved for primary progressive MS. The objective of this review is to present the modes of action of these drugs and their effects on the immunopathogenesis of MS. Each agent's clinical development and potential side effects are discussed.

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Section: Fingolimodmentioning

confidence: 84%

Immunological Aspects of Approved MS Therapeutics

et al. 2019

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“…Fingolimod (FTY720) is a food and drug administration (FDA)-approved drug for the treatment of multiple sclerosis (MS) in humans since 2011 and has evolved in recent years as the first-line oral medication for relapsing MS in clinical practice [ 5 ]. In target tissue, it can be converted to fingolimod phosphate, which is a potent modulator of sphingosine-1-phosphate receptors (S1PR 1–5 ); [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory Treatment with FTY720 Starting after Onset of Symptoms Reverses Synaptic Deficits in an AD Mouse Model

Kartalou

Salgueiro-Pereira

Endres

et al. 2020

IJMS

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Therapeutic approaches providing effective medication for Alzheimer’s disease (AD) patients after disease onset are urgently needed. Previous studies in AD mouse models suggested that physical exercise or changed lifestyle can delay AD-related synaptic and memory dysfunctions when treatment started in juvenile animals long before onset of disease symptoms, while a pharmacological treatment that can reverse synaptic and memory deficits in AD mice was thus far not identified. Repurposing food and drug administration (FDA)-approved drugs for treatment of AD is a promising way to reduce the time to bring such medication into clinical practice. The sphingosine-1 phosphate analog fingolimod (FTY720) was approved recently for treatment of multiple sclerosis patients. Here, we addressed whether fingolimod rescues AD-related synaptic deficits and memory dysfunction in an amyloid precursor protein/presenilin-1 (APP/PS1) AD mouse model when medication starts after onset of symptoms (at five months). Male mice received intraperitoneal injections of fingolimod for one to two months starting at five to six months. This treatment rescued spine density as well as long-term potentiation in hippocampal cornu ammonis-1 (CA1) pyramidal neurons, that were both impaired in untreated APP/PS1 animals at six to seven months of age. Immunohistochemical analysis with markers of microgliosis (ionized calcium-binding adapter molecule 1; Iba1) and astrogliosis (glial fibrillary acid protein; GFAP) revealed that our fingolimod treatment regime strongly down regulated neuroinflammation in the hippocampus and neocortex of this AD model. These effects were accompanied by a moderate reduction of Aβ accumulation in hippocampus and neocortex. Our results suggest that fingolimod, when applied after onset of disease symptoms in an APP/PS1 mouse model, rescues synaptic pathology that is believed to underlie memory deficits in AD mice, and that this beneficial effect is mediated via anti-neuroinflammatory actions of the drug on microglia and astrocytes.

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“…4 Interferons and glatiramer acetate are considered first-line treatment in patients with clinical isolated syndrome not fulfilling criteria for MS and patients with mild-moderate relapsing-remitting MS. 5 Other DMDs, such as natalizumab, fingolimod, and alemtuzumab, are recommended for patients with insufficient response to first-line treatments or those with high disease activity. [6][7][8][9][10] Although the newer drugs are highly efficacious, use of these DMDs requires careful patient monitoring, due to a higher risk of severe adverse events. 4,5 For instance, natalizumab and fingolimod have been associated with progressive multifocal leukoencephalopathy (PML), 11,12 a demyelinating and potentially fatal disease of the central nervous system.…”

Section: Introductionmentioning

confidence: 99%

<p>Drug-use patterns and severe adverse events with disease-modifying drugs in patients with multiple sclerosis: a cohort study based on German claims data</p>

Simbrich¹,

Thibaut²,

Khil³

et al. 2019

NDT

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Purpose: To describe drug-use patterns in patients with multiple sclerosis (MS) using disease-modifying drugs (DMDs) and to estimate the incidence of severe adverse events (SAEs) of treatment. Methods: We conducted a cohort study within the German Pharmacoepidemiological Research Database between January 1, 2006 and December 31, 2013. MS patients on DMDs were described in terms of clinical characteristics and drug-use patterns. Next, we assessed the incidence of AEs in new users of fingolimod, natalizumab, glatiramer acetate, and IFNβ 1a. Results: Among approximately 11 million insured members of German Statutory Health Insurance, the DMD-user cohort comprised 15,377 patients with MS, with a mean age of 39.6 years and 68% females. Nearly half of all DMD users had a diagnosis of depression, with prevalence ranging from 40.1% for IFNβ 1a to 62.3% for immunoglobulins. The overall rate of MS relapses per patient and year was 0.34 (95% CI 0.33-0.34). During an average follow-up of 1,650 days, the majority (42.4%) of MS patients were adherent to DMD treatment ("continuous single users"), followed by patients interrupting treatment (39.5%, "interrupters"). Switch of DMD treatment (11.9%) was less frequent, and only 5.6% discontinued treatment. Treatment discontinuation was most common in users of natalizumab (7.5%) and IFNβ 1b (7.0%). The most frequent SAE was hospitalization for depression, followed by any infectious disease and any malignancy. The incidence rate of all adverse events did not significantly differ across different DMDs. Conclusion: Treatment discontinuation with DMDs and treatment switch were rare. Causes of rather frequent DMD-treatment interruption have to be evaluated in further studies based on primary data collection. Active safety monitoring of new DMDs based on claims data requires large data sets to detect rare AEs and availability of up-to-date data.

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Long-term safety and real-world effectiveness of fingolimod in relapsing multiple sclerosis

Cited by 28 publications

References 48 publications

Immunological Aspects of Approved MS Therapeutics

Immunological Aspects of Approved MS Therapeutics

Anti-Inflammatory Treatment with FTY720 Starting after Onset of Symptoms Reverses Synaptic Deficits in an AD Mouse Model

<p>Drug-use patterns and severe adverse events with disease-modifying drugs in patients with multiple sclerosis: a cohort study based on German claims data</p>

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