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Long-Term Treatment Strategies of Pediatric Multiple Sclerosis, Including the use of Disease Modifying Therapies.

ABSTRACT: Multiple sclerosis (MS) presenting in the pediatric years can lead to landmark disability levels younger in life than adult onset MS and so therefore early and effective treatment remains paramount for long-term outcomes. The goals of MS therapeutics in adults have widened to address multiple mechanisms: anti-inflammatory, neuroprotective, and myelin repair, yet the optimal paradigm for MS therapies in the pediatric population is not known. Pediatric onset MS add complexities due to the ongoing development of the central nervous system and the immune system. Clinical trials have led to an increasing number of pharmaceutical therapies for adult onset MS (AOMS), one POMS randomized controlled trial is completed and other trials are ongoing, yet due to the low prevalence of POMS, the dynamic landscape and risk management of the MS disease modifying therapies (DMT) it remains more difficult to complete trials in POMS. There is consensus that controlled clinical trials leading to appropriate and safe therapies for POMS are important for a multitude of reasons that include unique pediatric pharmacokinetics, short and long-term safety, developmental issues, clinical benefits, and regulatory approval. This review will focus on new treatment goals, paradigm, strategies, monitoring, compliance, and products in the long-term treatment of POMS. The discussion will focus on these new concepts and the published data related to DMT use in POMS. This review provides significant insight into new concepts of treatment goals and current approaches to enhance the lives of the POMS patients now and in the future.

SUBMITTER: Rensel M

PROVIDER: S-EPMC6617229 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Long-Term Treatment Strategies of Pediatric Multiple Sclerosis, Including the use of Disease Modifying Therapies.

Rensel Mary M

Children (Basel, Switzerland) 20190531 6

Multiple sclerosis (MS) presenting in the pediatric years can lead to landmark disability levels younger in life than adult onset MS and so therefore early and effective treatment remains paramount for long-term outcomes. The goals of MS therapeutics in adults have widened to address multiple mechanisms: anti-inflammatory, neuroprotective, and myelin repair, yet the optimal paradigm for MS therapies in the pediatric population is not known. Pediatric onset MS add complexities due to the ongoing ...[more]

PMID: 31159312

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Project description:BackgroundAlthough relapsing-remitting multiple sclerosis (RRMS) has a chronic course, little information is known about the comparison between the disease-modifying therapies (DMT) for long-term outcomes. We aimed to conduct a systematic review of randomized clinical trial (RCT) extension and observational studies to examine the efficacy and safety of all available DMT for RRMS, compare the evidence with that derived from mid-term studies, and investigate whether the published long-term data are robust and reliable enough to inform clinical decision-making concerning RRMS treatment.MethodPubMed, Scopus, and manual searches were performed until October 2019. The clinical outcomes of long- and mid-term studies were compared. ROBINS-I was used to assess the methodological qualities of the long-term studies. PROSPERO number CRD42019123361.ResultsNineteen long-term studies (9,018 participants) were included in the systematic review. All studies presented serious or critical risks of bias that were mainly due to confounding, selection, and missing data biases. The annualised relapse rates (ARR) observed in the long-term studies are lower (better) than those from the mid-term studies for most treatments. The main reason for this ARR decrease could be a selection bias for good responders in the long-term studies, since many studies show a loss of patients between the mid- and long-term phases. The safety profiles depend on the study, follow-up, report, and outcome (i.e., discontinuation or number of patients with at least one serious adverse event).ConclusionThe currently available long-term data for patients with RRMS exhibit serious or critical risks of bias that preclude robust comparisons between long-term studies. High quality comparative observational studies with long-term follow-ups or RCT extensions with intention-to-treat analyses are needed to support clinical and regulatory practice. Until reliable long-term evidence is available, neurologists should continue to base their conduct on mid-term studies, patient`s experience and, most importantly, patient`s needs and predictor factors, according to personalized medicine.

Project description:BackgroundDisease-modifying therapies (DMTs) for multiple sclerosis (MS) target immunity and have the potential to increase the risk of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and alter its clinical course. We assessed these risks in patients with MS (PwMS).ObjectiveThe objective of this study was to describe the overall risk of coronavirus disease 2019 (COVID-19) infection, severe disease course, and potential population-level predictors of COVID-19 infection in PwMS, and to provide a context using a cohort of patients with systemic lupus erythematosus (SLE). In addition, the association of different MS DMTs with the incidence and clinical course of COVID-19 was evaluated. Safety data from the Biogen Global Safety Database are also presented on reported cases of COVID-19 in patients treated with Biogen MS therapies.MethodsThe IBM® Explorys electronic health record database of > 72,000,000 patients from US healthcare networks identified patients with MS or SLE, with and without polymerase chain reaction-confirmed COVID-19. COVID-19 cumulative incidence, hospitalization, and deaths among DMT classes were compared using logistic regression (adjusted for age, sex, body mass index, comorbidities, and race/ethnicity). As a secondary data source to assess safety data, COVID-19 reports for Biogen MS therapies were extracted and described from Biogen's Global Safety Database.Results30,478 PwMS with an open DMT prescription were identified within Explorys; 344 were COVID-19 positive. The most significant risk factors for acquiring COVID-19 were comorbidity score ≥ 1, body mass index ≥ 30, and Black/African ancestry. Similar risk factors were also identified for patients with SLE. Patients with MS were less likely to develop COVID-19 when treated with interferons (0.61%) and glatiramer acetate (0.51%), vs all other MS DMTs (both p < 0.001); anti-CD20 therapy was associated with the highest risk (3.45%; p < 0.0001). In the Biogen Global Safety Database, we identified 1217 patients who were COVID-19 positive treated with intramuscular interferon beta-1a, peginterferon beta-1a, natalizumab, dimethyl fumarate, diroximel fumarate, or fampridine.ConclusionsComorbidities, obesity, and Black/African ancestry, but not age, were associated with a higher risk of SARS-CoV-2 infection in PwMS. Interferons and glatiramer acetate were associated with a reduced COVID-19 risk, whereas anti-CD20 therapies were associated with an increased risk, within the treated MS cohort. COVID-19 safety reports for patients receiving Biogen MS therapies were consistent with the Explorys database and MS literature, illustrating the replicability and power of this approach.

Project description:ImportanceCognitive impairment in multiple sclerosis (MS) can lead to reduced quality of life, social functioning, and employment. Few studies have investigated cognitive outcomes among patients with pediatric-onset MS (POMS) over the long term.ObjectiveTo compare long-term information-processing efficiency between patients with POMS and adult-onset MS (AOMS).Design, setting, and participantsThis population-based longitudinal cohort study accessed the Swedish MS Registry (SMSreg), which collates information from all 64 neurology clinics in Sweden. Registered cases with definite MS in the SMSreg with an onset before April 15, 2018, and at least 2 Symbol Digit Modalities Test (SDMT) scores recorded were included. Only persons aged 18 to 55 years and with duration of disease of less than 30 years at the time of SDMT administration were included, to ensure comparable ranges between patients with POMS and AOMS. Of 8247 persons with an SDMT recorded in the SMSreg, 5704 met inclusion criteria, 300 (5.3%) of whom had POMS. Data were collected from April 1, 2006, through April 15, 2018 and analyzed from April through August 2018.ExposuresPediatric-onset MS (onset <18 years of age) vs AOMS (onset ≥18 years of age).Main outcomes and measuresInformation-processing efficiency measured every 6 or 12 months by the SDMT. Linear mixed-effects models were used to compare all available SDMT scores between patients with POMS and those with AOMS. Persons with cognitive impairment (ever vs never) were identified using regression-based norms and compared between POMS and AOMS groups using logistic regression.ResultsOf the 5704 participants, 4015 were female (70.4%), and 5569 had a relapsing-onset disease course (97.6%). Most participants were exposed to a disease-modifying therapy (DMT) during follow-up (98.8%). Median age at baseline for the POMS group was 25.6 years (interquartile range, 21.0-31.7 years) and for the AOMS group, 38.3 years (interquartile range, 31.4-45.2 years). A total of 46 429 unique SDMT scores were analyzed. After adjustment for sex, age, disease duration, disease course, total number of SDMTs completed, oral or visual SDMT form, and DMT exposure, the SDMT score for patients with POMS was significantly lower than that of patients with AOMS (β coefficient, -3.59 [95% CI, -5.56 to -1.54]). The SDMT score for patients with POMS declined faster than that of patients with AOMS (β coefficient, -0.30 [95% CI, -0.42 tp -0.17]). The odds of cognitive impairment were also significantly elevated in the POMS group (odds ratio, 1.44; 95% CI, 1.06-1.98).Conclusions and relevanceIn adulthood, patients with POMS demonstrated a more rapid reduction in information-processing efficiency over time and were more likely to experience cognitive impairment than patients with AOMS, independent of age or disease duration. Further investigation is required to understand the mechanisms by which early MS onset influences cognitive outcomes.

Dataset Information

Long-Term Treatment Strategies of Pediatric Multiple Sclerosis, Including the use of Disease Modifying Therapies.

Publications

Long-Term Treatment Strategies of Pediatric Multiple Sclerosis, Including the use of Disease Modifying Therapies.

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