Multiple sclerosis (MS) with onset before the age of 18 years is characterised by higher relapse rates and more severe MRI evidence of inflammation compared to adult-onset MS. Only persons older than 18 years have been included in randomised placebo-controlled trials; however, previous observational studies have shown that early initiation of disease-modifying therapy (DMT) may be beneficial for children with MS. No official international treatment guidelines are available for paediatric-onset MS (POMS), and there is limited evidence of DMT in children with MS.
The aim of this study was to describe DMT in POMS in Denmark from 1996, when DMT became available, until data were sourced in May 2017.
We conducted a nationwide population-based cohort study using prospectively collected real-world data derived from the Danish Multiple Sclerosis Registry. We identified a cohort of 195 children diagnosed with MS before 18 years of age. Since recording of all patients treated with DMT is mandatory in Denmark, the cohort is considered effectively complete.
Out of 195 patients, 123 (63%) started DMT before turning 18 years of age. The group of treated patients had a mean age at diagnosis of 14.9 years and a mean age at treatment initiation of 15.9 years (median: 16 years; range: 4–17 years). Most of the children received a first-line DMT, with IFN-β being the most common choice (85%). IFN-β1a administered subcutaneously was the most commonly used treatment from 1996–2005 (53%), while IFN-β1a administered intramuscularly was more common from 2006–2015 (59%). From 2011–2015, only 1 (2%) patient started treatment with dimethyl fumarate and 5 (9%) patients with teriflunomide. Two patients received induction therapy with mitoxantrone (in 2005). Natalizumab was the only second-line agent used as a primary treatment and was given to 6 children after 2011.
During the 20 years follow-up, a total of 107 (87%) children switched DMT or discontinued treatment, either due to adverse events or disease breakthrough. Of the 123 treated POMS cases, 39 children (32%) received >1 DMT before turning 18 years of age. The mean number of DMT per child, initiated before the age of 18 years, was 1.4. Natalizumab and fingolimod were used as second-line DMT in 18 out of 39 subjects. Fingolimod was prescribed more frequently than natalizumab when escalation of therapy was indicated, and three patients switched from natalizumab to fingolimod. IFN were used in 10 children (26%) after the first switch.
In conclusion, this study based on real-world data provides an insight into the patterns of use of DMT in POMS in Danish clinics.