Once upon a time there was a boy. He lived in a well-to-do neighborhood, had everything that he needed, his parents loved him and everything was possible. One day whilst playing football his leg gave way and he could no longer walk like his mates. This was the start of his journey into MS and adulthood.
Age matters in MS. Pediatric MS typically refers to the development of MS before 18 years of age. For many years owing to study specific requirements and the ethical dilemmas of conducting clinical trials in children, drug development in the pediatric population could only be termed mediocre at best. MS is no different in this whilst highly active treatments have been available in adults for more than two decades, the only licensed therapies in children were injectables (demonstrated to have ~30% relapse rate reduction in adults). This was the case until 2018 when fingolimod became the first highly active DMT to be approved in children and adolescents over the age of >10 years.
Tysabri, alemtuzumab or ocrelizumab on the other hand aren’t. Tysabri’s label reads as follows: “The safety and efficacy of TYSABRI in children and adolescents up to 18 years have not been established. No recommendation on a posology (countable pharmacology) can be made.” One would need to brave the evidence free zone and utilize the medication off-label. ‘Off-label’ simply refers to the use of a medication in a way different to that described in its license. The data collected is not as robust as a randomized controlled study, but falls under the jurisdiction of real world data collected in practice. One of the main issues is the potential for selection bias (not getting the full picture by selecting individuals that are included and not randomly) with this type of data, but not everyone has the money or resources to run a clinical trial.
However, in so far as natalizumab is concerned below is a publication from a very small study of 21 patients in Portugal (see below for the abstract). Following natalizumab, the relapse rate dropped from 1.31 events/person/year to 0.04 after 24 months. NEDA-3 (no evidence of clinical or MRI activity) was 100% at 12 months and 75% at 24 months, whilst the disability score decreased from 1.66 to 1.39 on average (see figure below). The only serious adverse event was the development of pneumonia whilst being treated. By no means there have been larger studies than this, the largest including 100 patients from Italy, which showed similar outcomes.
With enough users off-label use becomes acceptable for daily practice, but at some point someone will have to do that randomized controlled study.
Mult Scler Relat Disord. 2021 Feb 24;51:102865. doi: 10.1016/j.msard.2021.102865. Online ahead of print.
TyPed study: Natalizumab for the treatment of pediatric-onset multiple sclerosis in Portugal
Background: A significant proportion of pediatric-onset multiple sclerosis (POMS) patients do not respond to first-line disease-modifying therapies. Clinical trials showed that natalizumab is effective and safe in adults, but there are limited clinical trial data for children. Natalizumab is currently prescribed off-label for POMS. We aimed to characterize the effectiveness, safety and tolerability of natalizumab in all POMS cases treated in Portugal (from 2007 to 2018).
Methods: Data from clinical records were retrospectively collected for all POMS cases treated with natalizumab in Portugal.
Results: Twenty-one patients were included, 14 (67%) of which were female. The median age at POMS diagnosis was 13 years old. The median duration of treatment with natalizumab was 2 years and 3 months. Median Expanded Disability Status Scale score decreased from 1.5 to 1.0 after 24 months. The Annualized Relapse Rate decreased from 1.31 events/patient/year before treatment with natalizumab to 0 after 12 months of treatment and to 0.04 after 24 months. No gadolinium-enhancing lesions or new or enlarged T2 hyperintense lesions were observed in 8/8 patients (100%) after 12 months, and 4/5 (80%) after 24 months. There was one possible serious adverse event, which did not require dose adjustment. Five patients discontinued treatment due to positive anti-JCV (JC virus) antibody JC serostatus.
Conclusion: Natalizumab may be an effective and safe disease-modifying therapy for POMS. Our results are in line with data published for the adult population, as well as with similar observational studies in pediatric populations in other regions.