Background: Paediatric onset multiple sclerosis (POMS) is a rare disease , as the estimated annual incidence of POMS ranges between 0.13 and 0.6 /100.000. Patients with an onset before 18 years represent 3-5% of total MS population. POMS have a higher relapse rate compared with adult-onset multiple sclerosis, suggesting that this is a more inflammatory form of disease. To date, injectable therapies such as interferon-beta (IFN-beta) products (IFNb-1a intramuscular, and subcutaneous, IFNb-1b sc) and glatiramer-acetate (GA) are the only approved drugs by EMA for POMS and therefore the most commonly used treatments in this paediatric population. The positive effect of these drugs in reducing relapse rate and delaying disease progression, with a generally favourable safety profile, has been demonstrated in retrospective and prospective observational studies and in some unblinded RCTs conducted in patients with an age at onset between 12-18 years. Only few studies included POMS patients with age less of 12 years. To date, which is the best injectable therapy for controlling disease activity and progression in treatment-naïve POMS has never been assessed. Objectives: the main aim is: to compare safety and clinical effectiveness on the disease course between the IFN-beta 1a weekly i.m. and GA in relapsing-remitting (RR) POMS according to MRI data. Secondary aims are: to compare the efficacy of IFN-b products and GA on the annualize relapse rate (ARR), cognitive, behavioural and patient reported outcomes. Methods: a pragmatic head-to-head trial will be conducted. RR POMS aged from 10 to less than 18 years old will be recruited in some of the MS centres (21) belonging to the national network of the Italian MS Registry. This study is a 36-month multi-centre randomized interventional pragmatic trial to evaluate the effectiveness and safety of GA compared to IFN-beta in children/adolescent patients aged 10-17 (i.e. have not yet had their 18th birthday at randomization) with MS. The study consists of two phases: a pre-randomization phase consisting of screening and baseline data collection and a treatment phase. Clinical, cognitive, behavioural and MRI data will be collected at the baseline and at each follow-up visit; these data will be included into the Italian MS Register (a web application of this registry is in progress). Clinical evaluation will be performed at baseline and every six months and it will include: complete medical history, physical and neurological examination, with disability assessed by the Expanded Disability Status Scale (EDSS), annualised relapse rate (including the year prior randomisation), quality of life measured by the Pediatric Quality of Life (PQoL) scale, fatigue assessed by the Modified Fatigue Impact Scale(MFIS), vital signs, haematological/blood chemistry, urinalysis and pregnancy test. Brain MRI scan (by 1.5 T MRI) cognitive , using the Symbol Digit Modalities Test (SDMT)will be assessed at baseline and every 12 months. Expected results: we expect to demonstrate the equivalence or statistical significant differences between IFN-beta 1a weekly i.m. and GA treatments on the efficacy and safety outcomes.

Multi-centre, randomised, open label pragmatic trial to compare the effectiveness and safety of interferon-beta 1a (IFN-beta 1a) weekly i.m. and glatiramer-acetate (GA) in paediatric patients affected by multiple sclerosis

Agnese Suppiej
2017

Abstract

Background: Paediatric onset multiple sclerosis (POMS) is a rare disease , as the estimated annual incidence of POMS ranges between 0.13 and 0.6 /100.000. Patients with an onset before 18 years represent 3-5% of total MS population. POMS have a higher relapse rate compared with adult-onset multiple sclerosis, suggesting that this is a more inflammatory form of disease. To date, injectable therapies such as interferon-beta (IFN-beta) products (IFNb-1a intramuscular, and subcutaneous, IFNb-1b sc) and glatiramer-acetate (GA) are the only approved drugs by EMA for POMS and therefore the most commonly used treatments in this paediatric population. The positive effect of these drugs in reducing relapse rate and delaying disease progression, with a generally favourable safety profile, has been demonstrated in retrospective and prospective observational studies and in some unblinded RCTs conducted in patients with an age at onset between 12-18 years. Only few studies included POMS patients with age less of 12 years. To date, which is the best injectable therapy for controlling disease activity and progression in treatment-naïve POMS has never been assessed. Objectives: the main aim is: to compare safety and clinical effectiveness on the disease course between the IFN-beta 1a weekly i.m. and GA in relapsing-remitting (RR) POMS according to MRI data. Secondary aims are: to compare the efficacy of IFN-b products and GA on the annualize relapse rate (ARR), cognitive, behavioural and patient reported outcomes. Methods: a pragmatic head-to-head trial will be conducted. RR POMS aged from 10 to less than 18 years old will be recruited in some of the MS centres (21) belonging to the national network of the Italian MS Registry. This study is a 36-month multi-centre randomized interventional pragmatic trial to evaluate the effectiveness and safety of GA compared to IFN-beta in children/adolescent patients aged 10-17 (i.e. have not yet had their 18th birthday at randomization) with MS. The study consists of two phases: a pre-randomization phase consisting of screening and baseline data collection and a treatment phase. Clinical, cognitive, behavioural and MRI data will be collected at the baseline and at each follow-up visit; these data will be included into the Italian MS Register (a web application of this registry is in progress). Clinical evaluation will be performed at baseline and every six months and it will include: complete medical history, physical and neurological examination, with disability assessed by the Expanded Disability Status Scale (EDSS), annualised relapse rate (including the year prior randomisation), quality of life measured by the Pediatric Quality of Life (PQoL) scale, fatigue assessed by the Modified Fatigue Impact Scale(MFIS), vital signs, haematological/blood chemistry, urinalysis and pregnancy test. Brain MRI scan (by 1.5 T MRI) cognitive , using the Symbol Digit Modalities Test (SDMT)will be assessed at baseline and every 12 months. Expected results: we expect to demonstrate the equivalence or statistical significant differences between IFN-beta 1a weekly i.m. and GA treatments on the efficacy and safety outcomes.
2017
2019
Nazionale
Responsabile di Unità locale
Nessun Finanziamento
Suppiej, Agnese
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2401532
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