Consensus statement: evaluation of new and existing therapeutics for pediatric multiple sclerosis

Abstract

New therapies are being evaluated by clinical trials and, if efficacious, introduced for the treatment of adult MS. The role of these new and existing agents in the management of pediatric MS has yet to be defined. Pediatric investigation plans are now required by the Food and Drug Administration and European Medicines Agency for approval of new biological agents, providing an important opportunity to gather much-needed data for clinicians caring for children and adolescents with MS. However, challenges include the small number of patients, and the need for efficient yet comprehensive study designs incorporating factors necessary to inform the clinical care of children with MS. The elected Steering committee of the International Pediatric MS Study Group (IPMSSG) conducted a structured review of existing data on the disease-modifying therapies in pediatric MS and developed a consensus statement, which was further modified by the IPMSSG general membership, using an online survey tool. Fifty-one IPMSSG members from 21 countries responded to the survey, and 50 approved the final statement. Consensus recommendations regarding use of existing first- and second-line therapies, as well as a proposed definition for inadequate treatment response, are presented. Recommendations for the use and evaluation of emerging therapies (currently in phase III clinical trials or recently approved for adult MS) are discussed. The IPMSSG endorses the inclusion of pediatric MS patients in trials evaluating appropriate new and emerging therapies. Mechanisms for conducting high-impact, multicenter studies, including long-term follow-up in pediatric MS, are required to ensure that all MS patients, irrespective of age, benefit from advances in MS therapeutics.

Recovery From Central Nervous System Acute Demyelination in Children

“…Although randomized trials would provide evidence to support or refute the role of corticosteroids in acute management of ADS, endorsement of such a study is unlikely given the severity of acute illness and the strong international consensus regarding at least its short-term benefit. 18,19 There are limitations to our study. First, children with mild symptoms of ADS may have been missed; our research thus delineates the clinical severity and outcome of children unwell enough to seek medical attention.…”

“…Children with ADEM had the longest hospital stays, whereas children with ON had the shortest hospital stays ( Severe deficits in $1 feature of vision, motor, bladder and bowel function, or cognition were detected at ADS onset in 133 (47.0%) of 283 children, whereas 51 (18.0%) children had $1 moderate deficit, and 79 (27.9%) children had at least 1 mild deficit (Supplemental Fig 3A). Twenty (7.1%) children had a normal examination at study enrollment (days from onset, median [range]: 9 [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]); all had at least 1 deficit at onset verified according to records review of their presenting examination.…”

The heritage of glatiramer acetate and its use in multiple sclerosis

“…GA, along with IFN-β, has been recommended as the standard treatment for paediatric RRMS in two position papers, one produced by European experts [101] and the other one by the International paediatric MS Study [102]. Since paediatric onset MS is characterized by high disease burden, early treatment, although off-label, should be promptly started after confirmation of the diagnosis.…”

“…Since paediatric onset MS is characterized by high disease burden, early treatment, although off-label, should be promptly started after confirmation of the diagnosis. The favourable tolerability profile of GA should be considered when making a therapeutic choice [101,102].…”

Therapeutic Approach to the Management of Pediatric Demyelinating Disease: Multiple Sclerosis and Acute Disseminated Encephalomyelitis

“…For most presentations, intravenous (IV) corticosteroids are considered first-line treatment [40]. Corticosteroids have [13,29] been shown to accelerate the speed of recovery in addition to reducing the number of active, gadolinium-enhancing lesions on MRI within a few days post-treatment [41][42][43][44].…”