Safety Of Fingolimod In Patients Research Articles

Safety of fingolimod in patients with relapsing remitting multiple sclerosis: A descriptive analysis of data from the EudraVigilance database

The most prevalent disease course of Multiple Sclerosis (MS) is relapsing remitting multiple sclerosis (RRMS). Fingolimod (Gilenya®) was the first oral disease-modifying therapy to RRMS. Patients affected by MS require long-term treatment, making the ongoing evaluation of the safety profile of fingolimod imperative. The aim of this study was to analyze the post-marketing pharmacovigilance data of fingolimod in Europe.Data of 12-year period (1 January 2011–19 June 2023) were obtained from EudraVigilance, and a descriptive analysis using drug-reaction pairs was performed.A total of 22,957 reports were collected. The most reported adverse events (AEs) were related to nervous system disorders SOC (multiple sclerosis relapse n = 2271; 3.51%, headache n = 921; 1.42%, central nervous system lesion n = 893; 1,38%, dizziness 769; 1,19%, hypoaesthesia 487; 0.75% and multiple sclerosis 449; 0.69%), followed by investigations (lymphocyte count decreased n = 1648; 2.55%, white blood cell count decreased n = 833; 1.29%), blood and lymphatic system disorder (lymphopenia n = 1146; 1.77%), and general disorders and administration site condition (fatigue n = 1106; 1.71%, gait disturbance 564; 0.87%). A percentage of 23.00% of serious adverse events (SAEs), among the most reported were multiple sclerosis relapse (n = 2271; 15.27%), macular oedema (n = 793; 5.33%), bradycardia (n = 678; 4.56%), leukopenia (n = 533; 3.58%), and multiple sclerosis (n = 449; 3.02%).Most of AEs were non-serious, some SAEs related to cardiac, ophthalmic and infectious disorders emerged: their prevalence, along with the alignment of reported AEs with existing literature, supports the overall safety of fingolimod. Considering the rare and long-term ADRs that may arise in patients chronically treated for MS, continuous pharmacovigilance remains essential.

Real-world effectiveness and safety of fingolimod in patients with multiple\xa0sclerosis in the Czech Republic: results from core and extension parts of the GOLEMS study up to 48\xa0months

BackgroundFingolimod, an oral sphingosine 1-phosphate receptor immunomodulator, is approved in Europe for people with multiple sclerosis (pwMS) with highly active disease despite a full and adequate course of treatment with ≥ 1 disease-modifying therapy or patients with rapidly evolving severe relapsing–remitting MS. GOLEMS, a national, multicenter, non-interventional, single-arm, real-world study showed a favorable benefit–risk profile of 12-month treatment with fingolimod in pwMS in the Czech Republic. Here, we evaluated the long-term effectiveness and safety of fingolimod and its impact on disability progression and work capability for up to 48 months in pwMS.MethodsThe endpoints assessed were the incidence and severity of MS relapses in fingolimod-treated patients and the proportion of relapse-free patients up to 48 months of fingolimod treatment, change from baseline in the Expanded Disability Status Scale (EDSS) score, and change from baseline in work capability assessment. Efficacy outcomes were analyzed in the completed and efficacy sets, and safety was evaluated in all the enrolled patients.ResultsOf 240 enrolled patients, 237 were included into efficacy set. Patients with a minimum of a 12-month observation period in the core study who continued fingolimod treatment, were eligible to participate in the extension phase. Of 211 patients enrolled in extension study, 155 were evaluated in the completed set. Based on analysis of 48-month period of fingolimod treatment, 95/237 patients (40.1%) in the efficacy set, 54/155 (34.8%) in the completed set were free of relapses. The majority of relapses reported were moderate in intensity. Mean EDSS score remained stable throughout 48-month study period (Baseline, 3.4; Month 48, 3.6). No trend was observed in changes in work capability assessment or number of missed days of work. Of 240 enrolled patients, 147 (61.3%) had ≥ 1 treatment-emergent adverse event (AE) and 20 (8.3%) reported serious AEs. In total, 45 patients (18.8%) permanently discontinued treatment because of AEs related to study drug; two patients reported pregnancy after treatment initiation and subsequently discontinued the treatment; no deaths were reported.ConclusionGOLEMS study demonstrated the sustained effectiveness and manageable safety profile of fingolimod under real-world conditions over 48 months in patients with MS.Trial registrationNot applicable.

Safety of Fingolimod in Patients with Multiple Sclerosis Switched from Natalizumab: Results from TRANSITION-A 2-Year, Multicenter, Observational, Cohort Study.

Multiple sclerosis (MS) patients receiving natalizumab and who are at risk of developing progressive multifocal leukoencephalopathy (PML) often switch to other high-efficacy disease-modifying therapies including fingolimod as a risk mitigation strategy, which could impact treatment safety and effectiveness. The TRANSITION study aimed to evaluate the safety of fingolimod over two years in patients with MS after switching from natalizumab in a real-world setting. The safety and effectiveness were assessed by monitoring serious and other adverse events (SAEs, AEs). We assessed effectiveness by recording relapses, Expanded Disability Status Scale (EDSS) scores, and MRI activity. Of 637 patients enrolled, 505 completed the study (mean age, 42 years). Overall, 72.8% and 12.7% experienced AEs and SAEs respectively. The most common AEs were fatigue, headache, and urinary tract infection; no cases of PML were observed. Fingolimod treatment resulted in low disease activity. Patients with ≤8 weeks washout period had a markedly lower risk of relapses (4.5%) than those with >8 weeks (51.4%). In patients switching from natalizumab to fingolimod, no new safety signals with overall low relapse activity were observed in patients with washout latencies of ≤8 weeks before fingolimod initiation. Fingolimod was found to be safe and effective in patients transitioning from natalizumab.

Real-world retrospective study of effectiveness and safety of FINgOlimod in relapsing remitting multiple sclerosis in the Middle East and North Africa (FINOMENA)

ObjectivesEvidence on the effectiveness and safety of fingolimod in real-world clinical practice in the Middle East and North African (MENA) region is limited. This study aimed to evaluate the effectiveness and safety of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) in real-world setting in the MENA region. Patients and methodsRRMS patients who had been treated with fingolimod for at least 12 months were retrospectively identified from the databases of 34 centers across the MENA region. Study outcomes included the annualized relapse rate (ARR), relapse-free rate (RFR), time to first and second relapses, mean change in Expanded Disability Status Scale (EDSS), proportion of patients with Magnetic Resonance Imaging (MRI) activity and no evidence of disease activity (NEDA)-3, retention of patients on treatment, as well as all safety measures. ResultsA total of 806 patients were included: 66.34 % female; mean age 32.97 ± 9.62 years; mean disease duration 4.92 ± 4.66 years; mean fingolimod use 37.2 ± 16.7 months. Most patients had received previous disease-modifying therapy (79.65 %). Compared to the year preceding fingolimod initiation, RFR improved (33.00%–86.35%; p < 0.001), ARR decreased (0.84 ± 0.73 to 0.16 ± 0.45; p = 0.005), EDSS decreased (2.69 ± 1.74–2.01 ± 1.66; p < 0.001), and the proportion of patients with Gadolinium-enhancing T1 lesions decreased (57.84 % to 12.93 %; p < 0.001), after 12 months of fingolimod treatment. NEDA-3 was achieved in 41.3 % of patients. Median time to first and second relapses was not reached since 86.35 % and 98.39 % of patients had not experienced relapses for the first time and second time, respectively. Eight-hundred one (99.38 %) patients continued fingolimod treatment beyond 12 months. One-hundred thirty patients (16.13 %) experienced adverse events, mainly lymphopenia (5.46 %) and leukopenia (2.11 %), while 13 patients (1.61 %) experienced serious adverse events. ConclusionThis study confirms the effectiveness and safety profile of fingolimod in real-world setting in the Middle East and North African (MENA) region.

REALMS study: real-world effectiveness and safety of fingolimod in patients with relapsing-remitting multiple sclerosis in Portugal

BackgroundFingolimod, an oral sphingosine 1-phosphate receptor modulator, is approved by EMA for relapsing-remitting multiple sclerosis (RRMS).ObjectivesTo assess the effectiveness and safety of fingolimod in patients with RRMS in real-world clinical practice in Portugal.MethodsRetrospective, multicentre, non-interventional study, reporting 3 years follow-up of data collected from October 2015 to July 2016. Sociodemographic data and previous treatments at baseline and data regarding disease evolution, including number of relapses, annualised relapse rates (ARR) and Expanded Disability Status Scale (EDSS), were collected.ResultsTwo-hundred and seventy-five participants were enrolled in the REALMS study. Results showed that the main reason to switch to fingolimod was failure of previous treatment (56.7%) and only 3.6% were naïve patients. In the total population, there was a significant decrease in ARR of 64.6% in the first year of treatment, 79.7% in the second year and 82.3% in the third year, compared with baseline. More than 67.0% of patients had no relapses during the 3 years after switching to fingolimod. EDSS remained stable throughout the study.ConclusionsTherapy with fingolimod showed a sustained effectiveness and safety over the 3 years, particularly on patients switched from first-line drugs (BRACE). No new safety issues were reported.

The efficacy and safety of fingolimod in patients with relapsing multiple sclerosis: A meta-analysis.

The aim of the present meta-analysis was to evaluate the efficacy and safety of fingolimod in patients with relapsing multiple sclerosis (RMS). PubMed, Embase, the Cochrane Library and ClinicalTrials.gov were searched for relevant studies. Two authors independently selected the studies, assessed the risk of bias, and extracted the data. The meta-analysis was performed in RevMan 5.3 provided by the Cochrane Collaboration. Ten studies met the inclusion criteria. In patients with RMS, fingolimod demonstrated a significantly lower annualized relapse rate (0.5 mg/d: mean difference [95% confidence interval] = -0.22 [-0.29 to -0.14]; 1.25 mg/d: -0.26 [-0.36 to -0.16]; 5 mg/d: -0.41 [-0.72 to -0.10]) than placebo. Fingolimod also exhibited a favorable performance on other magnetic resonance imaging outcomes and improved the quality of life in patients. No significant difference was noted in the prevalence of adverse events between the fingolimod treatment group and the placebo/disease-modifying therapy groups. Fingolimod may offer benefits for RMS patients and presents an acceptable safety profile.

Real-World Effectiveness and Safety of Fingolimod in Patients With Relapsing Remitting Multiple Sclerosis: A Prospective Analysis in Buenos Aires, Argentina.

The aim of this prospective observational postmarketing study was to evaluate fingolimod effectiveness in a real-world setting in Buenos Aires, Argentina. Relapsing remitting multiple sclerosis patients who had been prescribed fingolimod owing to treatment failure and had at least greater than or equal to 24 months of follow-up were included during August 2013 and June 2018. Three-monthly clinical evaluations and 12-monthly magnetic resonance were performed. Demographic and clinical variables were described as well as the safety and the effectiveness outcomes that included the proportion of patients free from clinical relapses, from disability progression, from new or enlarging T2 or T1 gadolinium-enhancing lesions on annual magnetic resonance imaging, and from any disease activity during the follow-up. A total of 97 patients were included (68% female [n = 66]; mean ± SD age, 30 ± 10.5 years; mean ± SD disease duration, 6.5 ± 3.1 years; mean ± SD Expanded Disability Status Scale, 3.5 ± 1; mean ± SD fingolimod use, 30 ± 13 months [range, 18-56 months]). One hundred percent (97) used previous disease-modifying therapy, mainly interferons (87%; n = 84). Fourteen patients (14.4%) discontinued/withdrew fingolimod (10 owing to disease activity and 4 owing to tolerance and personal decisions). Eighty-two percent were free from clinical relapses, and 85% were free from disability progression; 75% of patients remained free from new or newly enlarging T2 lesions, and 78% of patients were free from gadolinium enhancing lesions. The proportion of patients free from any disease activity was 54%. The effectiveness of fingolimod in a newly real-world setting was consistent with information provided from phase III clinical trials.

Effectiveness and Safety of Fingolimod in Patients Switching from Dimethy Fumarate, Teriflunomide, and Daclizumab in Daily Clinical Routine: Interim Results from PANGAEA 2.0 (P3.2-075)

Effectiveness and Safety of Fingolimod in Patients Switching from Dimethy Fumarate, Teriflunomide, and Daclizumab in Daily Clinical Routine: Interim Results from PANGAEA 2.0 (P3.2-075)

Real World Retrospective Study of Effectiveness and Safety of Fingolimod in Relapsing Remitting Multiple Sclerosis in the Middle East and North Africa (FINOMENA)

Background: This study aimed to evaluate the effectiveness and safety of fingolimod in patients with RRMS in real-world setting in the mena region.

Efficacy and Safety of Fingolimod in Patients with Multiple Sclerosis

Background: In 2010, Fingolimod was the first oral disease modifying therapy approved for treatment of patients with relapsing multiple sclerosis.

Real-world experience of fingolimod in patients with multiple sclerosis (MS Fine): An observational study in the UK.

BackgroundFingolimod is approved for the treatment of highly active relapsing–remitting multiple sclerosis in Europe. There is limited information on its effectiveness and safety in clinical practice within the UK.ObjectiveTo evaluate retrospectively the effectiveness and safety of fingolimod in patients with relapsing–remitting multiple sclerosis who were prescribed fingolimod by UK neurologists within the National Health Service.MethodsThis was a multicentre, observational study conducted in the UK. Patients were initiated on fingolimod 0.5 mg 12 months before inclusion in the study. Key efficacy outcomes included annualised relapse rate and the proportion of patients free from relapses, disability progression and clinical and radiological disease activity at 12 months following fingolimod initiation. Resource utilisation and safety outcomes were also assessed.ResultsIn 12 months of treatment with fingolimod, the mean annualised relapse rate was reduced by 79%, the majority of patients were free from relapses (83.7%). Based on limited data, most patients were free from disability progression and clinical and radiological disease activity. More than 90% of patients continued on fingolimod. Lymphocyte count reductions and liver enzyme increases were observed.ConclusionFingolimod was effective in reducing the disease activity in relapsing–remitting multiple sclerosis patients requiring an escalation from first-line therapies who were prescribed fingolimod in clinical practice in the UK.

Intracerebral lymphoproliferative disorder in an MS patient treated with fingolimod.

Fingolimod, an oral sphingosine 1-phosphate (S1P) receptor modulator, is an effective oral immune therapy for treatment of relapsing-remitting MS (RRMS).1 Development of solid malignancies was observed in large randomized phase-3 trials examining the efficacy and safety of fingolimod in patients with RRMS.1 In this article, we present a patient who developed a primary central nervous system T-cell lymphoproliferative disorder during fingolimod treatment. The authors thank May H. Han for her critical reading of the article.

Effectiveness, safety and health-related quality of life of multiple sclerosis patients treated with fingolimod: results from a 12-month, real-world, observational PERFORMS study in the Middle East

BackgroundEvidence on the use of fingolimod in real-world clinical practice and data on patient-reported health-related quality of life (HRQoL) in countries such as the Middle East are sparse. The Prospective Evaluation of Treatment with Fingolimod for Multiple Sclerosis (PERFORMS) study assessed HRQoL and effectiveness and safety of fingolimod in patients with relapsing-remitting multiples sclerosis (RRMS), primarily in Middle Eastern countries.MethodsThis 12-month, observational, multicentre, prospective, real-world study was conducted in patients with RRMS who initiated fingolimod or another approved disease-modifying treatment (DMT) within 4 weeks before study entry. Patients were enrolled in a 2:1 ratio to obtain more data in fingolimod and parallel in other DMTs cohort by physicians during routine medical care. Key study outcomes included HRQoL assessed using MS International QoL (MusiQoL), MS relapses and disability. Safety was assessed throughout the study period. Due to the observational nature of the study, no neuroimaging assessments were mandated and central reading was not performed.ResultsOf 249 enrolled patients, 247 were included in the analysis (fingolimod cohort 172; other DMTs cohort 75). Overall, the mean age of patients was 36.5 years, 64.4% were women and ~90% were Caucasians. At baseline, mean MS duration since diagnosis was 7.2 years in the fingolimod and 4.8 years in the other DMTs cohorts. Overall, mean changes in MusiQoL index scores were −2.1 in the fingolimod cohort and −0.7 in the other DMTs cohort at Month 12, but improvement was not significant vs. baseline in both cohorts. Proportion of relapse-free patients increased significantly during the study vs. 0–12 months before the study in the fingolimod cohort (80.2% vs. 24.4%; p < 0.0001). Proportion of patients free from disability progression was 86.5% in the fingolimod cohort. The incidences of AEs were 59.9% and 50.6% in the fingolimod and other DMTs cohorts, respectively. First-dose monitoring of fingolimod observed no cases of symptomatic bradyarrhythmia. Three cases of bradycardia were reported in the fingolimod cohort: one after the first dose and two during the study. No cases of macular oedema were observed during the study.ConclusionsFingolimod treatment maintained QoL over 12 months and was effective in reducing relapse rate and disability progression. No new safety findings were observed in this real-world observational study in Middle Eastern countries.

The real-world effectiveness and safety of fingolimod in relapsing-remitting multiple sclerosis patients: An observational study.

Fingolimod approval was based mainly on two clinical trials, FREEDOMS and TRANSFORMS, which demonstrated the efficacy and safety of fingolimod in patients with multiple sclerosis (MS). We present an observational study that validates these trials findings in a real-world setting, whereby the effectiveness and safety of fingolimod was assessed in Seville’s’ (Spain) clinical practice.This retrospective study in MS patients assessed effectiveness (relapses, EDSS, gadolinium-enhancing T1 and new/enlarged T2-weighted lesions): total cohort (n = 249) and stratified according to prior treatment (glatiramer acetate/interferon beta-1 [immunomodulator], natalizumab, naïve), gender, basal EDSS score, basal Gd+ lesions, ARR prior to treatment, age at treatment initiation and number of prior treatments. A multivariante model was used to assess the ARR with baseline characteristics. The safety profile (adverse events [AEs]) was also described.Fingolimod reduced the annualized relapse rate (ARR) by 75%, 67% and 85% in the total cohort, patients previously treated with immunomodulatory and naïve patients (p<0.0001 all cases). However, patients previously treated with natalizumab kept a constant ARR. The ARR results and the consequent increase in the proportion of relapse-free patients were independent of the age at treatment initiation, number of prior treatments, gender and basal Gd+ lesions. Although fingolimod was effective regardless the basal EDSS score and ARR prior to fingolimod treatment, better outcomes were observed in patients with basal EDSS score <3 (0.2 vs. 0.4; p = 0.0244) and ARR ≥ 2 prior to fingolimod treatment (p = 0.0338). Only the basal EDSS score was association with ARR in the first 24 months of fingolimod treatment in the multivariante model (p = 0.0439). The cumulative probability of disability progression was 20% (month-24) in the total cohort, and was independent from prior treatment, age at treatment initiation, number of prior treatments, gender, basal EDSS score, basal Gd+ lesions and ARR prior to treatment.The real-world fingolimod benefits observed in this study seem to be similar than those observed in previous clinical trials.

Fingolimod: efectividad y seguridad en la práctica clínica habitual. Estudio observacional, retrospectivo y multicéntrico en Galicia

Introduction. The effectiveness and safety of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) have been proven in clinical trials. Yet,due to their limitations,it is important to know how it behaves under everyday clinical practice conditions. Hence,the aim of this study is to evaluate the effectiveness and safety of fingolimod after 12 months’ usage in clinical practice in Galicia. Patients and methods. We conducted a retrospective,multi-centre study (n = 8) of patients with RRMS who were treated with one or more doses of fingolimod,0.5 mg/day. Effectiveness was assessed -annualised relapse rate (ARR),changes in the score on the Expanded Disability Status Scale (EDSS),percentage of patients free from relapses,free from progression of disability and free from activity in resonance-for the total number of patients and according to previous treatment. Safety was assessed based on the percentage of patients who withdrew and presented adverse side effects. Results. After 12 months’ use,fingolimod reduced the ARR by 87% (1.7 to 0.23; p < 0.0001) and,consequently,81% of patients were free from relapses. The score was reduced by 9%. In all,91% of patients were free from progression of disability and 72% were free from resonance activity. No signs of disease activity were found in 43% of the patients. Most of the benefits of fingolimod differed depending on previous treatment. About a third of the patients reported adverse side effects,but only 2% of them withdrew for this reason. Conclusions. In clinical practice,most of the results on the effectiveness of the clinical trials conducted with fingolimod were observed during the first 12 months of treatment. A better safety profile was observed than that reported in the clinical trials.

Fingolimod for relapsing multiple sclerosis: an update

Importance of the field: Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the CNS. There is a large unmet need for new disease-modifying therapies with improved convenience, safety and efficacy. Fingolimod is an oral sphingosine-1-phosphase (S1P) receptor modulator under clinical investigation for the treatment of relapsing-remitting and primary progressive MS.Areas covered in this review: This review provides an update on the mechanism of action, pharmacological properties and efficacy and safety of fingolimod in patients with relapsing MS, with a particular emphasis on clinical trials.What the reader will gain: The reader will gain a comprehensive overview of the mechanism of action of fingolimod, particularly how the drug inhibits lymphocyte egress from secondary lymphoid organs by modulation of S1P receptors, and its pharmacokinetic and pharmacodynamic properties. Results from Phase II studies and pivotal Phase III trials of fingolimod for relapsing MS are discussed in depth.Take home message: Randomized clinical trials have demonstrated the superior efficacy of fingolimod in reducing relapse rates and MRI measures of disease activity, as compared with placebo and intramuscular IFN-β-1a. Fingolimod also lowered the risk of disability progression compared with placebo. Adverse events included bradycardia and atrioventricular block, respiratory and herpesvirus infections, increased liver enzyme levels, hypertension and macular edema. Fingolimod 0.5 mg seems to provide the best risk–benefit ratio.