Fingolimod In Relapsing-remitting Multiple Sclerosis Research Articles

Final results of the PANGAEA 2.0 study: Treatment benefits of fingolimod for active RRMS patients switching from other DMTs (P6-3.009)

<h3>Objective:</h3> The aim of the PANGAEA 2.0 study was to investigate the efficacy and long-term benefits (3 years) of fingolimod in relapsing-remitting multiple sclerosis (RRMS) patients with disease activity switching from other disease-modifying therapies (DMTs). <h3>Background:</h3> In the treatment of RRMS, individualized sequential therapies can be used to optimize the outcome. It is, however, necessary to understand the efficacy and overall impact of sequential switching. <h3>Design/Methods:</h3> The non-interventional, real-world evidence study included 2,579 disease-active RRMS-patients treated with fingolimod at 240 neurological practices and clinics in Germany out of which 966 completed the study. The patients, who were either untreated or treated with an approved DMT other than fingolimod before study start, were observed for 3 years. To obtain insight into the effectiveness of changing to fingolimod, subgroup analyses were based on the patients’ last therapy before switching: oral DMT (oDMT; dimethyl fumarate, teriflunomide), injectable DMT (iDMT; interferons, glatiramer acetate), natalizumab, other DMTs and treatment-naive. <h3>Results:</h3> At baseline, the patient population was mostly female (71.1%) and patients were on average 39.2 (±10.8) years old. The majority of patients had received only 1 treatment prior to study start. In total, 1,138 patients had received an iDMT as last therapy before receiving fingolimod. On average, patients presented with an EDSS of 2.4±1.5 at study start. Over 3 years, the mean EDSS total score remained on a relatively stable level in the subgroups iDMT (EDSS: 2.4±1.6) and oDMT (EDSS: 2.6±1.5). The EDSS increased slightly in the group who was previously on natalizumab treatment (EDSS: 3.3±1.6) along with a slight increase in FSMC. The mean SDMT remained on a stable level in all subgroups. <h3>Conclusions:</h3> PANGAEA 2.0 brings us real-world insights into the effectiveness of fingolimod in disease-active RRMS-patients. The results show that the disease burden remained relatively stable during 3 years on fingolimod, regardless of the previous therapy. <b>Disclosure:</b> Dr. Weiss has received personal compensation for serving as an employee of Novartis Pharma GmbH. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS Celgene. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Roche. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Novartis. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Ziemssen has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sanofi. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for BMS Celgene. Dr. Ziemssen has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Ziemssen has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for TEVA. The institution of Dr. Ziemssen has received research support from Biogen. The institution of Dr. Ziemssen has received research support from Novartis. The institution of Dr. Ziemssen has received research support from Merck. The institution of Dr. Ziemssen has received research support from Sanofi. The institution of Dr. Ziemssen has received research support from Celgene.

EE415 Cost Utility Analysis of Ocrelizumab Versus Fingolimod in Relapsing Remitting Multiple Sclerosis Patients in Egypt from Payor Perspective

The aim of this study is to compare cost utility of Ocrelizimuab versus Fingolimod in relapsing-remitting multiple sclerosis (RRMS) from Ministry of Health payor perspective in Egypt.

Different Doses of Fingolimod in Relapsing-Remitting Multiple Sclerosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: The efficacy and safety of fingolimod for relapsing-remitting multiple sclerosis (RRMS) had been well verified in several large randomized controlled trials (RCTs) during the past decade. However, there are fewer systematic comparisons of different doses of fingolimod and whether the dose of 0.5 mg/d is the optimal one still remains to be solved. Objective: The objective of this systematic review was to evaluate the efficacy and safety of the four existing doses of fingolimod in the treatment of RRMS, especially the dose of 0.5 mg/d. Methods: MEDLINE, EMBASE, Cochrane Library, and clinicaltrials.gov were searched for RCTs which were performed to evaluate different doses of fingolimod and the corresponding control (placebo or DMTs) up to October 2020. Review Manager 5.3 software was used to assess the data. The risk ratio (RR) and mean difference (MD) was analyzed and calculated with a random effect model. Results: We pooled 7184 patients from 11 RCTs. Fingolimod 0.5 mg/d was superior to control group in all eight efficacy outcomes including annualized relapse rate (ARR) (MD −0.22, 95%CI −0.29 to −0.14, p < 0.00001) but surprisingly showed a higher risk of basal-cell carcinoma (RR 4.40, 95%CI 1.58 to 12.24, p = 0.004). Although 1.25 mg/d is more than twice the dose of 0.5 mg/d, the effect size was almost similar between them. Dose of 5 mg/d obtained an unsatisfactory efficacy while showing a greater risk of adverse events than other three doses (RR 1.17, 95%CI 1.05 to 1.30, p = 0.003). Additionally, fingolimod 0.25 mg/d not only showed a better performance in delaying the disease progress of magnetic resonance imaging (MRI), but also achieved a certain degree of patient treatment satisfaction. Conclusion: At present, 0.5 mg/d remains to be the optimal dose of fingolimod for RRMS patients but trials of a lower dose are still of great clinical significance and should be paid more attentions.

Long-term comparative analysis of no evidence of disease activity (NEDA-3) status between multiple sclerosis patients treated with natalizumab and fingolimod for up to 4 years

BackgroundComparative effectiveness of natalizumab and fingolimod over a follow-up longer than 2 years has been not addressed yet.ObjectivesTo compare the effect on no evidence of disease activity (NEDA-3) in relapsing-remitting multiple sclerosis (RRMS) patients treated with natalizumab or fingolimod for at least 4 years.MethodsWe included RRMS patients switched from first-line agents to natalizumab or fingolimod. Patients were propensity score (PS)-matched on a 1-to-1 basis. Percentages of patients reaching NEDA-3 status at 2 and 4 years of follow-up were compared using the chi-square test. The risk of not achieving NEDA-3 at 4 years was explored in matched samples by Cox regression models.ResultsWe evaluated 174 PS-matched patients. Patients receiving natalizumab reached a NEDA-3 status at 2 and 4 years more frequently than those exposed to fingolimod (63% vs 44%, p=0.037; 45.7% vs 25.8%, p=0.015, respectively). Patients receiving natalizumab were at a significant lower risk of not achieving the NEDA-3 status at 4 years compared to those exposed to fingolimod (hazard ratio (95% confidence interval): 0.54 (0.36–0.80), p=0.002).ConclusionsAlthough both medications were effective in patients non-responding to first-line agents, natalizumab seems to be superior to fingolimod in RRMS in obtaining NEDA-3 status at 4 years.

Descriptive Analysis of Real-World Data on Fingolimod Long-Term Treatment of Young Adult RRMS Patients

Background: Fingolimod (Gilenya®) is approved for adult and pediatric patients with highly active relapsing–remitting multiple sclerosis (RRMS).Objectives: The objective was to describe the effectiveness of fingolimod in young adults compared to older patients in clinical practice.Methods: PANGAEA is the largest prospective, multi-center, non-interventional, long-term study evaluating fingolimod in RRMS. We descriptively analyzed demographics, MS characteristics, and severity in two subgroups of young adults (≤20 and >20 to ≤30 years) and older patients (>30 years).Results: Young adults had lower Expanded Disability Status Scale (EDSS) scores compared to older patients (1.8 and 2.3 vs. 3.2) at baseline. The mean EDSS scores remained stable over 5 years in all subgroups. Young adults had higher annual relapse rates (2.0 and 1.7 vs. 1.4) at study entry, which were reduced by approximately 80% in all subgroups over 5 years. The proportion of patients with no clinical disease activity in year 4 was 52.6 and 73.4 vs. 66.9% in patients ≤20, >20 to ≤30 years and >30 years, respectively. The symbol digit modalities test score increased by 15.25 ± 8.3 and 8.3 ± 11.3 (mean ± SD) from baseline in patients >20 to ≤30 and >30 years.Conclusions: Real-world evidence suggests a long-term treatment benefit of fingolimod in young RRMS patients.

Effects of Natalizumab and Fingolimod on Clinical, Cognitive, and Magnetic Resonance Imaging Measures in Multiple Sclerosis.

Studies comparing the effects of natalizumab and fingolimod in relapsing-remitting multiple sclerosis (RRMS) are limited. We aimed to compare natalizumab and fingolimod effects on clinical, neuropsychological, and MRI measures in RRMS patients after 2years of treatment. RRMS patients starting natalizumab (n = 30) or fingolimod (n = 25) underwent neurologic, neuropsychological, and brain MRI assessments at baseline, month (M) 6, M12, and M24. Volumes of lesions, brain, gray matter (GM), white matter (WM), and deep GM were measured. Fifteen healthy controls (HC) were also scanned at baseline and M24. Treatment groups were matched for baseline variables. At M24 versus baseline, both drugs reduced the relapse rate (p value < 0.001), stabilized disability, and improved cognitive function (fingolimod: p value = 0.03; natalizumab: p value = 0.01), without between-group differences. The natalizumab group had a higher proportion of freedom from MRI activity (67% vs 36%, p value = 0.02) and no evidence of disease activity-3 (NEDA-3) (57% vs 28%, p value = 0.04). At M24 vs M6, brain (- 0.35%, p value = 0.002 [fingolimod]; - 0.42%, p value < 0.001 [natalizumab]), GM (- 0.62%, p value < 0.001 [fingolimod]; - 0.64%, p value < 0.001 [natalizumab]), and WM (- 0.98%, p value < 0.001 [fingolimod]; - 0.99%, p value < 0.001 [natalizumab]) atrophy progressed at higher rates than in HC, but similarly between treatment groups, whereas only the natalizumab group showed deep GM atrophy (- 0.79%, p value = 0.02) (p value vs fingolimod not significant). In both groups, atrophy progression was correlated with lesion accumulation (r from - 0.49 to - 0.36, p values from 0.013 to 0.05), whereas no correlation was found between clinical and MRI changes. Natalizumab and fingolimod reduce disease activity and improve cognition in RRMS. Natalizumab seems superior to limit lesion accumulation, whereas both drugs similarly modify atrophy progression.

The real-world effectiveness of natalizumab and fingolimod in relapsing-remitting multiple sclerosis. An Italian multicentre study

BackgroundBoth natalizumab and fingolimod are highly effective in the treatment of relapsing-remitting MS (RRMS). In the absence of head-to-head trials, some observational studies have compared their efficacy with conflicting results. ObjectivesTo investigate the efficacy of natalizumab and fingolimod in a cohort of RRMS patients in an observational, retrospective study. MethodsWe included all consecutive RRMS patients who started natalizumab or fingolimod in three MS centres with a follow-up to 24 months and analysed clinical and brain MRI data after propensity score (PS) matching. ResultsAfter 1:1 PS-matching, we retained 102 patients in both groups, with similar baseline features. After 24 months, although both drugs resulted highly effective, patients treated with natalizumab had a lower relapse risk (HR 0.59 CI 95% 0.35–1.00, p = 0.048) and higher time to first relapse. MRI-combined-unique-activity was found in 31.8% of natalizumab vs 43.2% of fingolimod treated patients (p = 0.28). We found a higher proportion of patients with confirmed regression of disability (19.2 vs 6.7%, p = 0.03) and 2-year no evidence of disease activity (NEDA-3, 39.0% vs 22.0%, p = 0.04) in the natalizumab group. ConclusionsBoth drugs were highly effective in our cohort. Natalizumab proved superior in inducing regression of disability and 2-year-NEDA-3.

Efficacy and safety of alemtuzumab versus fingolimod in RRMS after natalizumab cessation

Natalizumab (NTZ) was the first approved monoclonal antibody for the treatment of relapsing-remitting multiple sclerosis (RRMS). Despite proven and sustained efficacy, its use is limited by the risk of progressive multifocal leukoencephalopathy (PML). Moreover, some patients show ongoing disease activity under NTZ, requiring a switch to another disease-modifying treatment (DMT). However, evidence regarding the optimal DMT for treatment of active RRMS after NTZ-cessation is still scarce. To evaluate efficacy and safety outcomes of ALEM vs FTY treatment after cessation of NTZ. We retrospectively identified patients at 12 German neurology centers and analyzed risks for disease activity, adverse events, disability progression, and treatment discontinuation. 195 patients were identified and 144 underwent final analysis (FTY: 101; ALEM: 42). The hazard ratio for clinical relapses was 2.24 favoring ALEM (95% CI 1.12-4.50; p = 0.015). The hazard ratio for adverse events was 7.78 (95% CI 1.04-57.95; p = 0.006) and 2.41 for MRI progression (95% CI 1.26-4.60; p = 0.004). The odds ratio for disability progression after 12months was 4.84 (95% CI 1.74-13.47, p = 0.003). Differences remained after adjusting for possible confounders (e.g., age, sex, baseline disability, NTZ treatment duration, washout time). Our findings indicated particular advantages of ALEM compared to FTY in patients stopping NTZ.

057 Real world evidence (RWE) on long-term persistence of fingolimod in relapsing-remitting multiple sclerosis (RRMS) in australia

IntroductionThis study aimed to examine and compare patient persistence of fingolimod to all reimbursed disease modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) in Australia.MethodThe Pharmaceutical Benefits Scheme (PBS) 10% sample supplied by the Department of Human Services was used in this study. Eligible patients must have received a script for a reimbursed DMT for RRMS between September 2011 and February 2016. Patient demographics were summarised using mean and standard deviation or frequency percentage. Persistence was defined as a patient that remained on a DMT with a gap in scripts of no longer than 4 months. Individual patients could be included multiple times if they initiated a new DMT during the study period. Persistence was derived using the Kaplan-Meier method and hazard ratios (HR). Persistence to individual treatments was then compared to the average persistence observed across all treatments; p-values were based on the log-rank test.Results720 unique patients were eligible for the study, contributing 1827 observations that for analysis (2.5 new initiations/patient). Overall the median persistence (MP) to therapy was 29.6 months with 67.7% of patients remaining on therapy for 12 months. The only DMT with significantly better persistence compared to the overall average was fingolimod (HR 0.65 (95%CI 0.57–0.73; p&lt;0.001). Patients had an MP of 60 months on fingolimod with 79.5% of patients persistent at 12 months. Patients were significantly less persistent to interferon Beta-1a, interferon Beta-1b, glatiramer acetate and dimethyl fumarate (hazard ratios above 1.27 (p values all≤0.001) whilst the remaining DMTs, teriflunomide and natalizumab, showed no significant difference from the average persistence.ConclusionIn this analysis of PBS sample data, patients were most persistent to fingolimod treatment amongst all DMTs.

Real World Evidence (RWE) on Long-Term Persistence of Fingolimod in Relapsing-Remitting Multiple Sclerosis (RRMS) in Australia

Real World Evidence (RWE) on Long-Term Persistence of Fingolimod in Relapsing-Remitting Multiple Sclerosis (RRMS) in Australia

Cardiac Safety Profile of First Dose of Fingolimod for Relapsing-Remitting Multiple Sclerosis in Real-World Settings: Data from a German Prospective Multi-Center Observational Study.

IntroductionFingolimod was the first oral therapy approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Due to its action on cardiac sphingosine 1-phosphate receptors, fingolimod is leading to a transient decrease in heart rate (HR) and the occurrence of rare and asymptomatic self-limited atrioventricular (AV) blocks. This German non-interventional clinical study aimed to assess the cardiac safety profile in RRMS patients during at least 6 h after the initial treatment or restart after interruption of fingolimod in real-world settings.MethodsThe GoCARD study (German National Health Authorities, BfArM, CFTY720DDE18, NIS334) was a prospective, multi-center non-interventional study which was conducted in neurological and other medical practices or hospitals, qualified to routinely assess electrocardiogram (ECG) findings. Data were collected through interviews, clinical evaluations (notably ECGs), and laboratory tests. Medical history, vital signs, and a 12-lead ECG were assessed before fingolimod administration. After the first dose, a 6 h ECG was performed and vital signs (blood pressure and HR) were measured hourly. The occurrence of bradycardia (HR ≤45 beats per minute [BPM]), AV blocks (2nd degree Mobitz type I or higher), and corrected QT interval (QTc) intervals was also documented.ResultsMore than 95% of physicians adhered to the cardiac monitoring recommendations. The observation of 217 patients in 42 study centers showed that while 35.9% of the patients had any cardiac risk profile, none of them experienced a bradycardia during the 6 h post-dose observation. Overall, only 1.8% of all patients displayed bradycardia (HR ≤45 BPM) during 6 h after treatment initiation. Moreover, in this cohort, none of the patients showed a new or persistent onset AV block (2nd degree Mobitz type I or higher) or QTc ≥500 ms.ConclusionAltogether, these data confirm that the first-dose observation after fingolimod initiation is usually uneventful (even in patients with pre-existing cardiovascular risk factors of this cohort) and that the rarely observed events remained asymptomatic and self-limited.FundingNovartis Pharma GmbH, Nürnberg, Germany.

Glioblastoma following treatment with fingolimod for relapsing-remitting multiple sclerosis

Glioblastoma is an uncommon and aggressive primary brain tumor with incidence of 3 per 100,000 annually. We report a 50-year-old woman diagnosed with glioblastoma within threeyears of induction of fingolimod therapy for relapsing-remitting multiple sclerosis. Fingolimod, an immunomodulating agent used in the treatment of relapsing-remitting multiple sclerosis, has also been suggested to impart a cardioprotective role in heart failure and arrhythmia via activation of P21-activated kinase-1 (Pak1). In the brain, Pak1 activation has been shown to correlate with decreased survival time amongst patients with glioblastoma. A molecular mechanism underlying a link between fingolimod use and glioblastoma development may involve activation of Pak1. To our knowledge, this is the first report of a potential association between fingolimod use and glioblastoma development.

Efficacy of Natalizumab and Fingolimod in Relapsing Remitting Multiple Sclerosis in Real World Clinical Setting

Objective: The aim of this study was to compare the efficacy of natalizumab and fingolimod in relapsing-remitting multiple sclerosis patients in real-world clinical setting. Methods: We enrolled 391 patients starting either natalizumab or fingolimod for relapsing-remitting multiple sclerosis, referred to four multiple sclerosis centers between March 2007 and July 2013. Cumulative proportion of patients free from any disease activity, as defined by freedom from relapse, Expanded Disability Status Scale (EDSS) progression, new or newly enlarging T2 lesions, and gadolinium enhancing lesions at magnetic resonance imaging (MRI) was assessed at 12-month follow-up. Results: Out of 391 patients, 197 were treated with natalizumab and 194 with fingolimod. The cumulative proportion of patients free from any disease activity was 72.0% in the natalizumab and 59.1% in the fingolimod group (P=0.014). This proportion was lower in fingolimod patients with prior natalizumab exposure compared to those without (51.7% vs. 61.8%; P=0.008). Moreover, the cumulative proportion of patients free from new MRI lesions was 87.5% in the natalizumab vs. 70.0% in the fingolimod group (P<0.001); the cumulative proportion of patients free from clinical relapse was 82.5% in the natalizumab vs. 81.3% in the fingolimod group (P=0.739); 93.5% of patients on natalizumab were free from EDSS progression compared to 89.6% of patients on fingolimod (P=0.186). Conclusions: Results from 1-year follow-up of treatment suggest higher efficacy of natalizumab compared to fingolimod in terms of proportion of patients free from any disease activity.

Second-Line Therapy with Fingolimod for Relapsing-Remitting Multiple Sclerosis in Clinical Practice: The Effect of Previous Exposure to Natalizumab

Background: To evaluate efficacy and safety of fingolimod for relapsing-remitting multiple sclerosis, particularly in patients previously exposed to natalizumab. Method: Prospective observational single-centre second-line cohort study. Results: Among 71 patients treated with fingolimod 0.5 mg/day for a mean duration of 21.75 w 12.60 months, the annualized relapse rate was 0.66 (C.I. 95% 0.27-1.05) with a significant difference between 26 patients with prior natalizumab exposure (1.15; C.I. 95% 0.12-2.17) and 45 not exposed (0.38; C.I. 95% 0.18-0.57; p = 0.002). In a multivariate negative regression model, only previous exposure to natalizumab (p = 0.049) and duration of fingolimod treatment (p < 0.001) significantly correlated with the annualized relapse rate. Previous exposure to natalizumab (p = 0.028) and duration of treatment with fingolimod (p < 0.001) were confirmed by restricting the analysis to the first 12 months of treatment with fingolimod, but were no longer statistically significant by analysing only patients (n = 51) with at least 12 months of treatment with fingolimod (0.32; C.I. 95% 0.08-0.55 vs. 0.22; C.I. 95% 0.11-0.32; p = NS). No differences were observed in neuroradiological outcomes and disability progression in patients exposed to natalizumab and not exposed. The rate of discontinuation due to adverse events was 11.3%, with no differences between the two groups. Conclusions: Our study confirms efficacy and side effects of fingolimod in a second-line clinical practice cohort. Prior natalizumab exposure and duration of treatment with fingolimod are independent predictors of annualized relapse rate during the first 12 months of treatment with fingolimod, but not in the long-term, and may be influenced by the 3 months washout period between the two drugs. i 2014 S. Karger AG, Basel

Effects of fingolimod in relapsing-remitting multiple sclerosis

Fingolimod, a sphingosine-1-phosphate receptor modulator, was the first oral drug to be approved for treatment of relapsing-remitting multiple sclerosis. Its approval was based on findings from the placebo-controlled FREEDOMS study of fingolimod 0·5 mg or 1·25 mg daily1 and those from a comparative trial of fingolimod versus interferon β-1a (30 μg weekly) given intramuscularly (TRANSFORMS),2 which both showed superiority of fingolimod. Because of safety issues, mainly cardiac symptoms associated with the first administration of fingolimod and two fatal cases of herpes virus infections, both occurring in patients treated with 1·25 mg, only 0·5 mg daily was approved, fingolimod was granted only second-line approval in the European Union, and the US Food and Drug Administration issued specific recommendations for monitoring patients and contraindications for use in some patients.

Long-Term Efficacy and Safety of Fingolimod (FTY720) in Relapsing-Remitting Multiple Sclerosis (RRMS): Results from the Extension of the Phase III FREEDOMS Study (S41.004)

Objective: To report long-term efficacy and safety of fingolimod in RRMS, from the phase III FREEDOMS study extension. Background RRMS patients randomized to oral, once-daily(o.d), fingolimod (0.5mg or 1.25mg) in the 2-year, double-blind, FREEDOMS core study, demonstrated a significant improvement in clinical and MRI endpoints versus placebo (PBO)-treated patients. We present here end of study (EOS) results from the extension phase of upto 4 years treatment. Design/Methods: In the extension, patients either continued on the core phase dose (continuous-fingolimod), or were re-randomized (1:1) from placebo to fingolimod (1.25 or 0.5mg/o.d) (PBO-fingolimod). All patients received open-label 0.5mg following a decision to discontinue the fingolimod 1.25mg/day treatment arm from all MS studies. Results: 1033/1272 (81.2%) patients enrolled in FREEDOMS completed the 24M core, and 773/920 (84%) patients enrolled in the extension (60.7% of initially randomized) completed the study. Common reasons for discontinuations were withdrawal of consent (7.2%) and adverse events (AE) (3.4%). Annualized relapse rates (ARR) decreased in the switch/PBO-fingolimod group during the extension phase (PBO-1.25mg, 0.22; PBO- 0.5mg, 0.19) versus the core (ARR= 0.4; p Conclusions: Patients who switched from placebo to fingolimod showed significant improvements in clinical and MRI outcomes (including brain atrophy). Continuous fingolimod treatment was associated with sustained low clinical and MRI disease activity and was well-tolerated. Supported by: Novartis Pharma AG, Basel, Switzerland. Disclosure: Dr. Kappos has received research support from Acorda Therapeutics, Actelion, Allozyne, BaroFold, Inc., Bayer Pharmaceuticals Corporation, Bayhill Therapeutics, Biogen Idec, Boehringer Ingelheim Pharmaceuticals, Inc, Elan Corporation, Genmab, GlaxoSmithKline, Inc., Glenmark Pharma, Merck Serono, MediciNova, Novartis, Sanofi-Aventis Pharmaceuticals, Santhera Pharmaceuticals, Shire, Roche Diagnostics, Teva Neuroscience, UCB Pharma, Pfizer Inc, Swiss MS Society, Swiss National Research Foundation, European Union, Gianni Rubatto Foundation, Novartis and Roche Research Foundations. Dr. Radue has received personal compensation for activities with AIM, Biogen Idec, and Novartis as a consultant.Dr. Radue has received research support from Actelion, Bayer Schering, Biogen Idec, Merck Serono, and Novartis. Dr. O9Connor has received personal compensation for activities with Abbott Labratories, Inc., Bayer Pharmaceuticals Corporation, Biogen Idec, BioMS, Cognosci, Daiichi Pharmaceuticals Corporation, Serono, Inc., Genentech, Inc., Genmab, Novartis, Roche Diagnostics Corporation, Sanofi-Aventis Pharmaceuticals, Inc., Teva Neuroscience, Warburg Pincus and Wyeth Pharmaceuticals as a consultant. Dr. O9Connor has received research support from Abbott Labratories, Bayer Pharmaceuticals Corporation, Biogen Idec, BioMS, Cognosci, Daiichi Pharmaceutical Corporation, Serono, Inc., Genentech, Inc., Genmab, Novartis, Roche Diagnostics Corporation, Sanofi-Aventis Pharmaceuticals, Teva Neuroscience, Warburg Pincus and Wyeth Pharmaceuticals. Dr. Polman has received personal compensation for activities with Biogen Idec, Schering AG, Teva Neuroscience, EMD Serono, Novartis, GlaxoSmithKline, Inc., UCB Pharma, AstraZeneca Pharmaceuticals, Roche Diagnostics and Antisense Therapeutics as a consultant or speaker.Dr. Polman has received research support from Biogen Idec, Schering AG, GlaxoSmithKline, Inc., Novartis, EMD Serono and Teva Neuroscience. Dr. Hohlfeld has received personal compensation for activities with Schering AG, Merck-Serono, Biogen Idec, Teva Neuroscience, Boehringer Ingelheim Pharmaceuticals, Inc.,Novartis, Sanofi-Aventis Pharmaceuticals, Inc. as a consultant and/or speaker. Dr. Hohlfeld has received personal compensation in an editorial capacity for International MS Journal.Dr. Hohlfeld has received research support from Schering AG, Merck-Serono, Biogen Idec, Teva Neuroscience, Norvartis. Dr. Calabresi has received personal compensation for activities with Teva, Biogen Idec, Novartis, Genzyme, Johnson & Johnson, and Vertex. Dr. Calabresi has received research support from Biogen Idec, Teva, EMD Serono, Vertex, Genentech, Abbott, and Bayer. Dr. Selmaj has received personal compensation for activities with Genzyme, Ono, and Biogen Idec. Dr. Agoropoulou has received personal compensation for activities with Novartis Pharma AG as an employee. Dr. Jin has received personal compensation for activities with Novartis Pharma AG. Dr. Zhang-Auberson has received personal compensation for activities with Novartis as an employee. Dr. Francis has received personal compensation for activities with Novartis as an employee. Dr. Francis holds stock and/or stock options in Novartis, which sponsored research in which Dr. Francis was involved as an investigator.

Evidence-based assessment of potential use of fingolimod in treatment of relapsing multiple sclerosis

Multiple sclerosis is an autoimmune inflammatory demyelinating disease of the central nervous system and represents one of the most common causes of chronic neurologic disability in young adults. All the current disease-modifying drugs are administered parenterally, and can be associated with varying degrees of injection site or infusion-related reactions. Together with other side effects, the parenteral route of administration is one of the key factors affecting adherence to therapy in multiple sclerosis. Fingolimod (FTY720) is an immunomodulator that acts on sphingosine 1-phosphate (S1P) receptors and is the first oral drug approved by the US Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis. Downmodulation of S1P receptor type 1 (S1P1) slows the egress of lymphocytes from lymph nodes and recirculation to the central nervous system, reduces astrogliosis, and inhibits angiogenesis during chronic neuroinflammation. Fingolimod also regulates the migration of B cells and dendritic cells, and enhances endothelial barrier function. Results from Phase II and III clinical trials provide robust evidence of the efficacy of fingolimod in relapsing-remitting multiple sclerosis. While some caution should be exercised in terms of safety issues, the introduction of fingolimod represents a great advance in the treatment of relapsing-remitting multiple sclerosis. The pharmacologic data on fingolimod and its efficacy and safety in multiple sclerosis are reviewed in this paper.