Delayed-Release Dimethyl Fumarate Safety and Efficacy in Pediatric Patients With Relapsing-Remitting Multiple Sclerosis
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...
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| Published in | Frontiers in neurology Vol. 11; p. 606418 |
|---|---|
| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
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Frontiers Media S.A
04.01.2021
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| Abstract | 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. |
|---|---|
| AbstractList | 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. 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.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. 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. 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). 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 ( = 20; 95% confidence interval: 66.8-92.8; < 0.0001) vs. the year before DMF initiation. 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. 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. |
| Author | Mazurkiewicz-Beldzinska, Maria Valis, Martin Alroughani, Raed Blaschek, Astrid Aaen, Gregory Beynon, Vanessa Pultz, Joe Huppke, Peter Peng, Xiaomei |
| AuthorAffiliation | 4 Department of Pediatric Neurology and Developmental Medicine, Hauner Children's Hospital, University of Munich , Munich , Germany 1 Dasman Diabetes Institute, Dasman, Kuwait and Amiri Hospital , Sharq , Kuwait 7 Biogen , Cambridge, MA , United States 6 Loma Linda University Children's Health , Loma Linda, CA , United States 5 Neurologicka klinika, Fakultni nemocnice Hradec Kralove , Hradec Kralove , Czechia 3 Klinika Neurologii Rozwojowej, Uniwersyteckie Centrum Kliniczne , Gdansk , Poland 2 Department of Pediatrics and Pediatric Neurology, University Medical Center Göttingen , Göttingen , Germany |
| AuthorAffiliation_xml | – name: 2 Department of Pediatrics and Pediatric Neurology, University Medical Center Göttingen , Göttingen , Germany – name: 6 Loma Linda University Children's Health , Loma Linda, CA , United States – name: 5 Neurologicka klinika, Fakultni nemocnice Hradec Kralove , Hradec Kralove , Czechia – name: 1 Dasman Diabetes Institute, Dasman, Kuwait and Amiri Hospital , Sharq , Kuwait – name: 3 Klinika Neurologii Rozwojowej, Uniwersyteckie Centrum Kliniczne , Gdansk , Poland – name: 4 Department of Pediatric Neurology and Developmental Medicine, Hauner Children's Hospital, University of Munich , Munich , Germany – name: 7 Biogen , Cambridge, MA , United States |
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| CitedBy_id | crossref_primary_10_1007_s40263_021_00887_w crossref_primary_10_1016_j_braindev_2021_12_010 crossref_primary_10_46563_2686_8997_2023_4_1_43_51 crossref_primary_10_1080_17512433_2025_2481868 crossref_primary_10_3389_fneur_2023_1207617 crossref_primary_10_1007_s40120_023_00565_7 crossref_primary_10_3390_ph15060753 crossref_primary_10_3390_sclerosis2020007 crossref_primary_10_1177_13524585241295554 crossref_primary_10_1001_jamanetworkopen_2022_30439 crossref_primary_10_3390_children12030259 crossref_primary_10_1177_17562864231177196 crossref_primary_10_1007_s40272_024_00675_1 crossref_primary_10_3390_ctn7010002 crossref_primary_10_1007_s40120_024_00633_6 crossref_primary_10_1007_s40267_022_00938_2 crossref_primary_10_17925_USN_2022_18_1_42 crossref_primary_10_1177_17562864231180734 crossref_primary_10_3389_fneur_2021_676095 crossref_primary_10_1007_s10072_022_06431_y crossref_primary_10_1016_j_clim_2022_108947 crossref_primary_10_1016_j_ijbiomac_2024_134908 |
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| Copyright | Copyright © 2021 Alroughani, Huppke, Mazurkiewicz-Beldzinska, Blaschek, Valis, Aaen, Pultz, Peng and Beynon. Copyright © 2021 Alroughani, Huppke, Mazurkiewicz-Beldzinska, Blaschek, Valis, Aaen, Pultz, Peng and Beynon. 2021 Alroughani, Huppke, Mazurkiewicz-Beldzinska, Blaschek, Valis, Aaen, Pultz, Peng and Beynon |
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| Keywords | pharmacokinetics dimethyl fumarate safety efficacy pediatric relapsing-remitting multiple sclerosis |
| Language | English |
| License | Copyright © 2021 Alroughani, Huppke, Mazurkiewicz-Beldzinska, Blaschek, Valis, Aaen, Pultz, Peng and Beynon. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Brahim Tabarki Melaiki, University of Sousse, Tunisia Reviewed by: Marcello Moccia, University of Naples Federico II, Italy; Renata Paolilo, Universidade de São Paulo, Brazil This article was submitted to Pediatric Neurology, a section of the journal Frontiers in Neurology |
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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... 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... 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... 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... |
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| Title | Delayed-Release Dimethyl Fumarate Safety and Efficacy in Pediatric Patients With Relapsing-Remitting Multiple Sclerosis |
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