Therapy of highly active pediatric multiple sclerosis

Huppke, Peter; Huppke, Brenda; Ellenberger, David; Rostásy, Kevin; Hummel, Hannah; Stark, Wiebke; Brück, Wolfgang; Gärtner, Jutta

doi:10.1177/1352458517732843

Cited by 67 publications

(53 citation statements)

References 19 publications

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“…A recent German study reported that 41.6% of patients with paediatric-onset multiple sclerosis fulfilled criteria for highly active disease. 32 There was no correlation between disease activity and sex or age at presentation. Lesion load at first MRI and disease activity in the first year can be suggestive of a highly active disease, and thus aid patient selection for the most effective therapies.…”

Section: Clinical Features and Disease Course: Does The Age Matter?mentioning

confidence: 88%

“…When age at onset was treated as a continuous variable, it reversely correlated with relapse rate. A recent German study reported that 41.6% of patients with paediatric‐onset multiple sclerosis fulfilled criteria for highly active disease . There was no correlation between disease activity and sex or age at presentation.…”

Section: Clinical Features and Disease Course: Does The Age Matter?mentioning

confidence: 99%

“…Another study compared paediatric patients with multiple sclerosis treated in 2005 with those treated in 2015. The results showed the relapse rate had reduced by 46% and the Expanded Disability Status Scale score by 44% . Of note, 44% of the 2015 group received second‐line therapy.…”

Section: Managementmentioning

confidence: 99%

“…In case of treatment failure, especially when clinical relapses have occurred and/or are increased in number, second‐line therapy may be considered. As paediatric‐onset multiple sclerosis is an active disease, up to 60% will require escalation to more effective therapy . In a recent randomized controlled trial comparing fingolimod with interferon‐ β 1a, fingolimod was associated with a lower rate of relapse and less accumulation of lesions on MRI over a 2‐year period; however, even on effective treatment (i.e.…”

Section: Managementmentioning

confidence: 99%

“…As paediatric-onset multiple sclerosis is an active disease, up to 60% will require escalation to more effective therapy. 32 In a recent randomized controlled trial comparing fingolimod with interferon-b1a, fingolimod was associated with a lower rate of relapse and less accumulation of lesions on MRI over a 2-year period; however, even on effective treatment (i.e. fingolimod), children continue to present with relapses and new MRI lesions.…”

Section: Environmental and Genetic Risk Factors: The Complex Interplaymentioning

confidence: 99%

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Paediatric multiple sclerosis: a new era in diagnosis and treatment

Duignan

Brownlee

Wassmer

et al. 2019

Develop Med Child Neuro

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Multiple sclerosis is a chronic immune‐mediated demyelinating disease of the central nervous system. The diagnosis of multiple sclerosis in children, as in adults, requires evidence of dissemination of inflammatory activity in more than one location in the central nervous system (dissemination in space) and recurrent disease over time (dissemination in time). The identification of myelin oligodendrocyte glycoprotein antibodies (MOG‐Ab) and aquaporin‐A antibodies (AQP4‐Ab), and the subsequent discovery of their pathogenic mechanisms, have led to a shift in the classification of relapsing demyelinating syndromes. This is reflected in the 2017 revised criteria for the diagnosis of multiple sclerosis, which emphasizes the exclusion of multiple sclerosis mimics and aims to enable earlier diagnosis and thus treatment initiation. The long‐term efficacy of individual therapies initiated in children with multiple sclerosis is hard to evaluate, owing to the small numbers of patients who have the disease, the relatively high number of patients who switch therapy, and the need for long follow‐up studies. Nevertheless, an improvement in prognosis with a globally reduced annual relapse rate in children with multiple sclerosis is now observed compared with the pretreatment era, indicating a possible long‐term effect of therapies. Given the higher relapse rate in children compared with adults, and the impact multiple sclerosis has on cognition in the developing brain, there is a question whether rapid escalation or potent agents should be used in children, while the short‐ and long‐term safety profiles of these drugs are being established. With the results of the first randomized controlled trial of fingolimod versus interferon‐β1a in paediatric multiple sclerosis published in 2018 and several clinical trials underway, there is hope for further progress in the field of paediatric multiple sclerosis. What this paper adds Early and accurate diagnosis of multiple sclerosis is crucial. The discovery of antibody‐mediated demyelination has changed the diagnosis and management of relapsing demyelination syndromes. Traditional escalation therapy is being challenged by induction therapy.

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Section: Clinical Features and Disease Course: Does The Age Matter?mentioning

confidence: 88%

Section: Clinical Features and Disease Course: Does The Age Matter?mentioning

confidence: 99%

Section: Managementmentioning

confidence: 99%

Section: Managementmentioning

confidence: 99%

Section: Environmental and Genetic Risk Factors: The Complex Interplaymentioning

confidence: 99%

See 3 more Smart Citations

Paediatric multiple sclerosis: a new era in diagnosis and treatment

Duignan

Brownlee

Wassmer

et al. 2019

Develop Med Child Neuro

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Risk of Persistent Disability in Patients With Pediatric-Onset Multiple Sclerosis

Baroncini¹,

Simone

Iaffaldano

et al. 2021

JAMA Neurol

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for the Italian MS registry IMPORTANCE Availability of new disease-modifying therapies (DMTs) and changes of therapeutic paradigms have led to a general improvement of multiple sclerosis (MS) prognosis in adults. It is still unclear whether this improvement also involves patients with pediatric-onset MS (POMS), whose early management is more challenging. OBJECTIVE To evaluate changes in the prognosis of POMS over time in association with changes in therapeutic and managing standards. DESIGN, SETTING, AND PARTICIPANTS Retrospective, multicenter, observational study. Data were extracted and collected in May 2019 from the Italian MS Registry, a digital database including more than 59 000 patients. Inclusion criteria were MS onset before age 18 years, diagnosis before January 2014, and disease duration of at least 3 years. Exclusion criteria were primary progressive MS, Expanded Disability Status Scale (EDSS) score of at least 8 one year after onset, unavailability of diagnosis date, and less than 2 EDSS score evaluations. Eligible patients were 4704 patients with POMS. According to these criteria, we enrolled 3198 patients, excluding 1506. EXPOSURES We compared time to reach disability milestones by epoch of MS diagnosis (<1993 , 1993-1999, 2000-2006, and 2007-2013), adjusting for possible confounders linked to EDSS evaluations and clinical disease activity. We then analyzed the difference among the 4 diagnosis epochs regarding demographic characteristics, clinical disease activity at onset, and DMTs management.MAIN OUTCOMES AND MEASURES Disability milestones were EDSS score 4.0 and 6.0, confirmed in the following clinical evaluation and in the last available visit. RESULTSWe enrolled 3198 patients with POMS (mean age at onset, 15.2 years; 69% female; median time to diagnosis, 3.2 years; annualized relapse rate in first 1 and 3 years, 1.3 and 0.6, respectively), with a mean (SD) follow-up of 21.8 (11.7) years. Median survival times to reach EDSS score of 4.0 and 6.0 were 31.7 and 40.5 years. The cumulative risk of reaching disability milestones gradually decreased over time, both for EDSS score of 4.0 (hazard ratio [HR],

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Highly Effective Therapies as First-Line Treatment for Pediatric-Onset Multiple Sclerosis

Benallegue,

Rollot,

Wiertlewski

et al. 2024

JAMA Neurol

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ImportanceModerately effective therapies (METs) have been the main treatment in pediatric-onset multiple sclerosis (POMS) for years. Despite the expanding use of highly effective therapies (HETs), treatment strategies for POMS still lack consensus.ObjectiveTo assess the real-world association of HET as an index treatment compared with MET with disease activity.Design, Setting, and ParticipantsThis was a retrospective cohort study conducted from January 1, 2010, to December 8, 2022, until the last recorded visit. The median follow-up was 5.8 years. A total of 36 French MS centers participated in the Observatoire Français de la Sclérose en Plaques (OFSEP) cohort. Of the total participants in OFSEP, only treatment-naive children with relapsing-remitting POMS who received a first HET or MET before adulthood and at least 1 follow-up clinical visit were included in the study. All eligible participants were included in the study, and none declined to participate.ExposureHET or MET at treatment initiation.Main Outcomes and MeasuresThe primary outcome was the time to first relapse after treatment. Secondary outcomes were annualized relapse rate (ARR), magnetic resonance imaging (MRI) activity, time to Expanded Disability Status Scale (EDSS) progression, tertiary education attainment, and treatment safety/tolerability. An adapted statistical method was used to model the logarithm of event rate by penalized splines of time, allowing adjustment for effects of covariates that is sensitive to nonlinearity and interactions.ResultsOf the 3841 children (5.2% of 74 367 total participants in OFSEP), 530 patients (mean [SD] age, 16.0 [1.8] years; 364 female [68.7%]) were included in the study. In study patients, both treatment strategies were associated with a reduced risk of first relapse within the first 2 years. HET dampened disease activity with a 54% reduction in first relapse risk (adjusted hazard ratio [HR], 0.46; 95% CI, 0.31-0.67; P &lt; .001) sustained over 5 years, confirmed on MRI activity (adjusted odds ratio [OR], 0.34; 95% CI, 0.18-0.66; P = .001), and with a better tolerability pattern than MET. The risk of discontinuation at 2 years was 6 times higher with MET (HR, 5.97; 95% CI, 2.92-12.20). The primary reasons for treatment discontinuation were lack of efficacy and intolerance. Index treatment was not associated with EDSS progression or tertiary education attainment (adjusted OR, 0.51; 95% CI, 0.24-1.10; P = .09).Conclusions and RelevanceResults of this cohort study suggest that compared with MET, initial HET in POMS was associated with a reduction in the risk of first relapse with an optimal outcome within the first 2 years and was associated with a lower rate of treatment switching and a better midterm tolerance in children. These findings suggest prioritizing initial HET in POMS, although long-term safety studies are needed.

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Therapy of highly active pediatric multiple sclerosis

Cited by 67 publications

References 19 publications

Paediatric multiple sclerosis: a new era in diagnosis and treatment

Paediatric multiple sclerosis: a new era in diagnosis and treatment

Risk of Persistent Disability in Patients With Pediatric-Onset Multiple Sclerosis

Highly Effective Therapies as First-Line Treatment for Pediatric-Onset Multiple Sclerosis

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