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Effect of Dimethyl Fumarate vs Interferon β-1a in Patients With Pediatric-Onset Multiple Sclerosis: The CONNECT
Patrick Vermersch1, Matthew Scaramozza2, Seth Levin2
1University Lille, Inserm, Centre Hospitalier Universitaire de Lille, Fédératif Hospitalo-Universitaire Precise, Lille, France.
Insights
Dimethyl fumarate (DMF) demonstrated greater efficacy than interferon beta-1a in reducing new T2 lesions and annualized relapse rates in pediatric multiple sclerosis patients. DMF was well-tolerated, offering a needed treatment option for this population.
Area of Science:
- Neurology
- Pediatric Neurology
- Immunology
Background:
- Limited approved multiple sclerosis therapies exist for pediatric patients.
- Pediatric-onset multiple sclerosis (POMS) requires effective and safe treatment options.
- Dimethyl fumarate (DMF) has limited data in POMS.
Purpose of the Study:
- To compare the efficacy, safety, and tolerability of DMF versus intramuscular interferon beta-1a (IFNβ-1a) in POMS.
- Evaluate lesion burden and relapse rates in pediatric MS patients treated with DMF or IFNβ-1a.
Main Methods:
- A 96-week, active-controlled, open-label, rater-blinded randomized clinical trial (CONNECT study).
- 150 patients (aged 10 to <18 years) with POMS were randomized to DMF or IFNβ-1a.
- Primary endpoint: proportion of patients free of new or newly enlarging T2 hyperintense lesions at week 96.
Main Results:
- More patients on DMF were free of new/enlarging T2 lesions (16.1% vs 4.9% in completers).
- DMF showed a lower adjusted annualized relapse rate (ARR) (0.24 vs 0.53).
- Treatment-emergent adverse events and discontinuations were similar between DMF and IFNβ-1a groups.
Conclusions:
- DMF is more effective than IFNβ-1a in reducing MRI lesion activity in POMS.
- DMF demonstrates a favorable safety and tolerability profile in pediatric MS patients.
- DMF represents a valuable therapeutic option for POMS.
Importance:
With 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).
Objective:
To compare the efficacy, safety, and tolerability of DMF vs intramuscular interferon β-1a (IFNβ-1a) in POMS.
Design, Setting, And Participants:
The 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.
Interventions:
Patients were randomized to DMF or IFNβ-1a.
Main Outcomes And Measures:
The 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.
Results:
Among 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 Relevance:
This 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 Registration:
ClinicalTrials.gov Identifier: NCT02283853.
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