&lt;p&gt;Review Of The Safety, Efficacy And Tolerability Of Fingolimod In The Treatment Of Pediatric Patients With Relapsing-Remitting Forms Of Multiple Sclerosis (RRMS)&lt;/p&gt;

Feng, Jenny; Rensel, Mary

doi:10.2147/phmt.s220817

Cited by 11 publications

(8 citation statements)

References 26 publications

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“…Overall, the results of this retrospective registry study are consistent with previous studies of natalizumab 13,[22][23][24][25][26][27][28][29][30] and fingolimod in patients with POMS, and therefore entirely expected. 21,[42][43][44][45][46] The results are also generally consistent with comparative studies of natalizumab and fingolimod in adult patients with MS, in concordance with the general agreement that pediatric-and adult-onset MS have similar underlying pathophysiology 14 and that outcomes for patients <18 years are not fundamentally different than those for patients >18 years, although data supporting this point are limited.…”

Section: (Which Was Not Certified By Peer Review)supporting

confidence: 80%

Comparative effectiveness of natalizumab and fingolimod and injectable therapies in patients with pediatric multiple sclerosis: A registry-based retrospective cohort study

Spelman

Simoneau²,

Hyde

et al. 2022

Preprint

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Background and Objectives: Patients with pediatric-onset multiple sclerosis (POMS) typically experience higher levels of inflammation with more frequent relapses and reach irreversible disability at a younger age than adult-onset patients. There have been few randomized placebo-controlled clinical trials of multiple sclerosis (MS) disease-modifying therapies (DMTs) in patients with POMS, and most available data are based on observational studies of off-label use of DMTs approved for adults. We assessed the effectiveness of natalizumab compared with fingolimod using injectable platform therapies as a reference in pediatric patients in the global MSBase registry. Methods: This retrospective study included patients with POMS who initiated treatment with an injectable DMT, natalizumab, or fingolimod between January 1, 2006, and May 3, 2021 (N=1218). The primary outcome was the time to first relapse from index therapy initiation. Secondary study outcomes included annualized relapse rate; proportions of relapse-free patients at 1, 2, and 5 years post baseline; time to treatment discontinuation; and times to 24-week confirmed disability worsening and confirmed disability improvement. Results: Patients treated with fingolimod had a significantly lower risk of relapse than patients treated with injectable DMT (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.29-0.83; P=0.008). After adjustment for prior DMT experience in the unmatched sample, patients treated with natalizumab had a significantly lower risk of relapse than patients treated either with injectable DMT (HR, 0.15; 95% CI, 0.07-0.31; P<0.001) or fingolimod (HR, 0.37; 95% CI, 0.14-1.00; P=0.049). The adjusted secondary study outcomes were generally consistent with the primary outcome or with previous observations. The findings in the inverse probability treatment weighting–adjusted patient populations were confirmed in multiple sensitivity analyses. Discussion: Our results suggest that natalizumab and fingolimod have broadly equivalent therapeutic efficacies in patients with POMS, consistent with previous studies of natalizumab and fingolimod in adult-onset patients and POMS. However, analyses of relapse outcomes suggest natalizumab is superior to fingolimod in the control of relapses in this population with high rates of new inflammatory activity. Classification of Evidence: This study provides Class III evidence that natalizumab may provide better disease control than fingolimod in patients with POMS.

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Section: (Which Was Not Certified By Peer Review)supporting

confidence: 80%

Comparative effectiveness of natalizumab and fingolimod and injectable therapies in patients with pediatric multiple sclerosis: A registry-based retrospective cohort study

Spelman

Simoneau²,

Hyde

et al. 2022

Preprint

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“…9 As a result, there is a shortage of approved treatment options for POMS, and therapies licensed for use in adults, including interferon β, dimethyl fumarate (DMF), fingolimod, glatiramer acetate, natalizumab, and teriflunomide, have been used off label. However, licensed therapies for pediatric patients are now emerging, with fingolimod approved in 2018 by the US Food and Drug Administration and the European Medicines Agency for patients with multiple sclerosis (MS) aged 10 to 17 years, 10 while teriflunomide was approved by the European Medicines Agency in 2021 for use in patients with relapsing-remitting MS (RRMS) aged 10 to 17 years. 9,11 DMF is an oral DMT approved for adults with relapsing forms of MS.…”

Section: Introductionmentioning

confidence: 99%

Effect of Dimethyl Fumarate vs Interferon β-1a in Patients With Pediatric-Onset Multiple Sclerosis

et al. 2022

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ImportanceWith few approved multiple sclerosis therapies in the pediatric population, there is a need for further approved treatment options. Limited data exist for dimethyl fumarate (DMF) treatment in pediatric-onset multiple sclerosis (POMS).ObjectiveTo compare the efficacy, safety, and tolerability of DMF vs intramuscular interferon β-1a (IFNβ-1a) in POMS.Design, Setting, and ParticipantsThe CONNECT study was an active-controlled, open-label, rater-blinded 96-week randomized clinical trial in patients with POMS aged 10 to less than 18 years treated between August 2014 and November 2020. Data were analyzed from January through October 2021.InterventionsPatients were randomized to DMF or IFNβ-1a.Main Outcomes and MeasuresThe primary end point was the proportion of patients free of new or newly enlarging (N or NE) T2 hyperintense lesions at week 96 among trial completers. Secondary end points included number of N or NE T2 lesions, proportion of patients free of relapse, annualized relapse rate (ARR), and safety. The estimated proportion of participants who were relapse free up to week 96 was calculated based on the Kaplan-Meier method. Adjusted ARR was obtained from a negative binomial regression adjusted for baseline relapse rate, baseline Expanded Disability Status Scale (EDSS) score, and age group.ResultsAmong 150 patients with POMS in the intention-to-treat (ITT) population (median [range] age, 15 [10-17] years; 101 [67.3%] female patients), 78 individuals received DMF and 72 individuals received IFNβ-1a. At week 96, the proportion of patients with no N or NE T2 hyperintense lesions among 103 trial completers was 16.1% (95% CI, 8.0%-27.7%) for DMF vs 4.9% (95% CI, 0.6%-16.5%) for IFNβ-1a, and in a sensitivity analysis among the ITT population, the proportions were 10 patients receiving DMF (12.8%) vs 2 patients receiving IFNβ-1a (2.8%). The estimated proportion of patients who remained relapse free at week 96 was 66.2% for DMF vs 52.3% for IFNβ-1a. Adjusted ARR (95% CI) at week 96 was 0.24 (95% CI, 0.15-0.39) for DMF vs 0.53 (95% CI, 0.33-0.84) for IFNβ-1a; the rate ratio for DMF vs IFNβ-1a was 0.46 (95% CI, 0.26-0.80; P = .006). The number of treatment-emergent adverse events (TEAEs; 74 patients [94.9%] vs 69 patients [95.8%]), serious TEAEs (18 patients [23.1%] vs 21 patients [29.2%]), and treatment discontinuations due to TEAEs (5 patients [6.4%] vs 8 patients [11.1%]) was similar for DMF vs IFNβ-1a.Conclusions and RelevanceThis study found that more pediatric patients with POMS treated with DMF were free of new or newly enlarging T2 lesions and that the adjusted ARR was lower among these patients compared with those treated with interferon β-1a. DMF was well tolerated.Trial RegistrationClinicalTrials.gov Identifier: NCT02283853

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“…Rituximab is not approved by the US Food and Drug Administration for the treatment of patients with MS, but has been studied in small trials of pediatric patients, showing it to be safe and effective ( 21 ). Fingolimod is the only MS therapy currently approved by both the US Food and Drug Administration and the European Medicines Agency for use in pediatric patients 10–17 years of age ( 22 ) on the basis of the positive outcome of a randomized controlled trial ( 23 ).…”

Section: Introductionmentioning

confidence: 99%

Delayed-Release Dimethyl Fumarate Safety and Efficacy in Pediatric Patients With Relapsing-Remitting Multiple Sclerosis

Alroughani

Huppke

Mazurkiewicz‐Bełdzińska³

et al. 2021

Front. Neurol.

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Background: Pediatric multiple sclerosis (MS) is rare: only 1.5–5% of MS cases are diagnosed before 18 years of age, and data on disease-modifying therapies (DMTs) for pediatric MS are limited. The CONNECTED study assessed the long-term safety and efficacy of treatment with delayed-release dimethyl fumarate (DMF), an oral MS DMT, in pediatric patients with MS.Methods: CONNECTED is the 96-week extension to FOCUS, a 24-week phase 2 study of patients aged 13–17 years; participants received DMF 240 mg twice daily. Endpoints included (primary) incidence of adverse events (AEs), serious AEs, and DMF discontinuations due to an AE, and (secondary) T2 hyperintense lesion incidence by magnetic resonance imaging and annualized relapse rate (ARR).Results: Twenty participants [median (range) age, 17 (14–18) years; 65% female] who completed FOCUS enrolled into CONNECTED; 17 (85%) completed CONNECTED. Eighteen participants (90%) experienced AEs: the most frequent was flushing (25%). None experienced infections or fever related to low lymphocyte counts. Three participants experienced four serious AEs; none led to DMF discontinuation. Twelve of 17 participants (71%) had no new/newly enlarged T2 lesions from weeks 16–24, two (12%) had one, and one each (6%) had two, three, or five or more lesions [median (range), 0 (0–6)]. Over the full 120-week treatment period, ARR was 0.2, an 84.5% relative reduction (n = 20; 95% confidence interval: 66.8–92.8; p < 0.0001) vs. the year before DMF initiation.Conclusions: The long-term safety and efficacy observed in CONNECTED was consistent with adults, suggesting pediatric and adolescent patients with MS might benefit from DMF treatment.

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<p>Review Of The Safety, Efficacy And Tolerability Of Fingolimod In The Treatment Of Pediatric Patients With Relapsing-Remitting Forms Of Multiple Sclerosis (RRMS)</p>

Cited by 11 publications

References 26 publications

Comparative effectiveness of natalizumab and fingolimod and injectable therapies in patients with pediatric multiple sclerosis: A registry-based retrospective cohort study

Comparative effectiveness of natalizumab and fingolimod and injectable therapies in patients with pediatric multiple sclerosis: A registry-based retrospective cohort study

Effect of Dimethyl Fumarate vs Interferon β-1a in Patients With Pediatric-Onset Multiple Sclerosis

Delayed-Release Dimethyl Fumarate Safety and Efficacy in Pediatric Patients With Relapsing-Remitting Multiple Sclerosis

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