The real-life experience with cardiovascular complications in the first dose of fingolimod for multiple sclerosis

Fragoso, Yára Dadalti; Arruda, Christian Cardoso; Arruda, Walter Oleschko; Brooks, Joseph Bruno Bidin; Damasceno, Alfredo; Damasceno, Carlos Augusto de Albuquerque; Finkelsztejn, Alessandro; Finkelsztejn, Juliana; Gama, Paulo Diniz da; Giacomo, Maria Cristina B.; Gomes, Sidney; Gonçalves, Marcus Vinícius Magno; Matta, André Palma da Cunha; Morais, Marilia Manprim de; Oliveira, Enedina Maria Lobato de; Ribeiro, Yuna; Sato, Henry Koiti; Tauil, Carlos Bernardo

doi:10.1590/0004-282x20140102

Cited by 14 publications

(13 citation statements)

References 9 publications

(13 reference statements)

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“…All 3 participating sites capably facilitated the FDO procedure. Our data, which are in line with the phase 3 trial data [ 3 , 4 ] and other FDO related real-world observational studies [ 6 , 7 ], show that despite strict FDO guidelines in Switzerland, initiation of fingolimod therapy can also take place in clinical settings (MS centre, day clinic, private practice) outside of University Hospitals with a reasonable workload. They also support the safety and feasibility of FDO as well as the good tolerability profile of fingolimod in these real-world clinical settings, as shown by rates of adverse events and drop-outs comparable to those published previously [ 3 , 4 ], supporting the fact that fingolimod can safely be used in MS centres, day clinics and private practices.…”

Section: Discussionsupporting

confidence: 87%

A Swiss real world best practice experience in three different clinical settings of the 6 hour fingolimod first dose observation procedure

Ramseier

Roth²,

Czapliński³

2015

BMC Pharmacol Toxicol

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BackgroundThe Swiss label of oral fingolimod (0.5 mg once daily) requires a 6-hour first dose observation (FDO) including an ECG prior to and 6 hours after the first intake but in comparison to other countries such as Austria, Australia and Canada there are no restrictions regarding the clinical settings of the FDO procedure in Switzerland. We present here our real-world experience of the 6 hour FDO procedure in three different clinical settings, following fingolimod treatment initiation. This is the first report on the FDO of fingolimod in these real-world clinical settings in Swiss patients with multiple sclerosis (MS).MethodsThis was a retrospective, multi-clinic, observational study of 136 patients with relapsing-remitting multiple sclerosis. Summary statistics have been used to present the data.ResultsOnly two patients (<1.5% [2/136]) experienced symptoms after the first dose of fingolimod. Atrioventricular conduction abnormalities were reported in 3% (4/136) of patients, which resolved spontaneously within 24 hours of treatment initiation. During the average 6.8 months follow-up, 96% (131/136) of the patients remained on therapyConclusionsThese findings support the safety and feasibility of FDO and tolerability of fingolimod in real-world clinical settings.

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Section: Discussionsupporting

confidence: 87%

A Swiss real world best practice experience in three different clinical settings of the 6 hour fingolimod first dose observation procedure

Ramseier

Roth²,

Czapliński³

2015

BMC Pharmacol Toxicol

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“…A US study (n = 317) reported that adverse events during first-dose observation were self-limited and included symptomatic bradycardia (n = 3), chest tightness (n = 2) and hypertension (n = 1) [97]. In a Brazilian study (n = 180), five patients had high BP and four had right or left branch block before medication; they were kept under observation for longer than 6 h and did not develop complications [98]. Two patients had sinus tachycardia and two had sinus bradycardia at the first ECG registration; they did not develop complications.…”

Section: Fingolimodmentioning

confidence: 99%

“…Two patients had sinus tachycardia and two had sinus bradycardia at the first ECG registration; they did not develop complications. Twelve (6.7%) other patients were kept under medical observation for longer than 6 h due to symptomatic bradycardia; 3 (1.7%) of them needed intensive care unit treatment for right branch block or second-degree AV block [98]. Another retrospective study (n = 212) considered the long-term cardiac safety of fingolimod.…”

Section: Fingolimodmentioning

confidence: 99%

Cardiac Autonomic Dysfunction in Multiple Sclerosis: A Systematic Review of Current Knowledge and Impact of Immunotherapies

Findling

Hauer

Pezawas

et al. 2020

JCM

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Cardiac autonomic dysfunction (CAD) has been reported in patients with multiple sclerosis (MS). This systematic review summarizes the evidence for the types and prevalence of CAD in MS patients, as well as its association with MS type, disease characteristics, fatigue and immunotherapies used to treat MS. The analysis revealed that CAD is correlated with pathophysiological processes of MS, can trigger serious cardiovascular complications that may reduce life expectancy, and may have implications for treatment with immunotherapies, especially fingolimod. Numerous mainly small case-control or cohort studies have reported various measures of CAD (particularly heart rate variation) in MS patients, showing higher rates of abnormality versus controls. A smaller number of studies have reported on cardiac autonomic symptoms in MS, including orthostatic intolerance/dizziness in around 50% of patients. CAD also appears to be associated with disease duration and to be more common in progressive than relapsing-remitting MS. However, although a substantial evidence base suggests that assessing CAD in people with MS may be important, standardised methods to evaluate CAD in these patients have not yet been established. In addition, no studies have yet looked at whether treating CAD can reduce the burden of MS symptoms, disease activity or the rate of progression.

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“…Extended monitoring due to prolonged bradycardia was required in three patients; however, none of the patients developed symptomatic bradycardia [ 16 ]. In a retrospective chart review of first-dose experience from several Brazilian clinics ( n = 180 RRMS patients), 99.4% of patients continued fingolimod treatment after the initial dose, and extended monitoring due to symptomatic bradycardia was required for 12 patients (6.7%) [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Safety and Tolerability of Fingolimod in Latin American Patients with Relapsing-Remitting Multiple Sclerosis: The Open-Label FIRST LATAM Study

Ordoñez-Boschetti¹,

Rey

Cruz³

et al. 2015

Adv Ther

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IntroductionFingolimod 0.5 mg is an orally active sphingosine 1-phosphate receptor modulator approved for use in adults with relapsing multiple sclerosis (MS). The efficacy and safety profile of fingolimod has been well characterized in a large clinical development program. Here, we report the safety and tolerability of fingolimod in relapsing-remitting MS (RRMS) patients from Latin America.MethodsA total of 162 patients with RRMS, predominantly from Latin American countries (138/162), were enrolled in this 16-week, single treatment arm, open-label, multi-center study. Unlike the phase III pivotal studies, this study permitted enrollment of patients with controlled diabetes, certain cardiac and pulmonary conditions, older age, and higher baseline Expanded Disability Status Scale. All patients were monitored clinically for a minimum of 6 hours after the first dose. Safety and tolerability assessments were based on adverse events, clinically notable laboratory abnormalities, vital signs, ophthalmic examinations, and electrocardiograms.ResultsOverall, the safety and tolerability profile was consistent with that reported previously in phase 3 studies and the FIRST study. Adverse events (AEs) were predominantly mild (n = 49, 35.5%) or moderate (n = 27, 19.6%). Three patients (2.2%) discontinued fingolimod due to AEs. Infections were reported in 33 patients (23.9%) and were predominantly mild in nature (n = 28, 20.3%). Increases in alanine aminotransferase enzymes of ≥3, ≥5 and ≥10 upper limit of normal were reported in five (3.7%), three (2.2%) and one (0.7%) patients, respectively. Hypertension cases (n = 3; 2.2%) did not result in treatment discontinuation and were controlled with antihypertensive therapy. Following first-dose administration, the majority of patients (90.6%) were discharged at 6 h. During the first-dose monitoring, 5 cases of bradycardia were reported; none required extended monitoring or treatment for symptomatic bradycardia.ConclusionThe first dose of fingolimod 0.5 mg was well tolerated in RRMS patients from Latin America. The overall safety profile was clinically manageable and consistent with previous fingolimod studies.FundingNovartis.Trial registration: ClinicalTrials.gov #NCT01497262.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-015-0224-2) contains supplementary material, which is available to authorized users.

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The real-life experience with cardiovascular complications in the first dose of fingolimod for multiple sclerosis

Cited by 14 publications

References 9 publications

A Swiss real world best practice experience in three different clinical settings of the 6 hour fingolimod first dose observation procedure

A Swiss real world best practice experience in three different clinical settings of the 6 hour fingolimod first dose observation procedure

Cardiac Autonomic Dysfunction in Multiple Sclerosis: A Systematic Review of Current Knowledge and Impact of Immunotherapies

Safety and Tolerability of Fingolimod in Latin American Patients with Relapsing-Remitting Multiple Sclerosis: The Open-Label FIRST LATAM Study

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