Treatment of Early Onset Multiple Sclerosis with Suboptimal Dose of Interferon Beta-1a

Pakdaman, Hossein; Fallah, A.; Sahraian, Mohammad Ali; Pakdaman, R.; Meysamie, Ali Pasha

doi:10.1055/s-2006-924723

Cited by 38 publications

(30 citation statements)

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“…24,26 In one unblinded study, 16 patients were randomized to intramuscular IFN-b-1a, half of adult dose, once a week or to no treatment. After 4 years, relapse rates (p 5 0.04), disability progression (p 5 0.01), and new T2 lesions (p 5 0.006) were lower in treated vs untreated patients.…”

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“…After 4 years, relapse rates (p 5 0.04), disability progression (p 5 0.01), and new T2 lesions (p 5 0.006) were lower in treated vs untreated patients. 26 In another study, controls were extracted from a database: after a mean follow-up of 5.5 years, patients treated with IFN-b demonstrated significantly reduced occurrence of relapses, especially in the first 2 years of exposure, and a decrease in development of severe disability, although not statistically significant 24 (table 1). Most studies have demonstrated a favorable effect of IFN-b on pediatric MS evolution, with a decline of relapse rate during the treatment phase, compared to the pretreatment period.…”

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Pediatric multiple sclerosis

et al. 2016

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Many disease-modifying therapies are currently available for adults with relapsing-remitting multiple sclerosis (MS) but none of them has been tested in pediatric MS in randomized placebo-controlled trials. At present, as suggested by observational studies and experts' guidelines, interferon-b and glatiramer acetate continue to be the standard first-line treatments for pediatric MS. Observational studies and some controlled unblinded trials have shown a positive effect of these meditations in reducing relapse rate and delaying disease progression, with an acceptable safety profile. The goal of this article is to provide an overview of current knowledge with regard to safety, tolerability, and efficacy of first-line treatment options for MS in the pediatric age group, with the aim of providing guidance for planning first-line treatment of MS in children and adolescents. Neurology ® 2016;87 (Suppl 2):S97-S102 GLOSSARY DMT 5 disease-modifying therapies; GA 5 glatiramer acetate; IFN-b 5 interferon-b; MS 5 multiple sclerosis; NAb 5 neutralizing antibodies; RRMS 5 relapsing-remitting multiple sclerosis.Many disease-modifying therapies (DMT) are currently available for adults with relapsing-remitting multiple sclerosis (RRMS), including interferon-b (IFN-b) 1a/1b, glatiramer acetate (GA), teriflunomide, dimethyl fumarate, natalizumab, fingolimod, and alemtuzumab. Their effectiveness has been demonstrated by phase 3 studies and by observational postmarketing studies for some. [1][2][3][4][5] IFN-b, GA, and teriflunomide have also been tested in patients with clinically isolated syndrome (CIS), and have been found to reduce the risk of a subsequent attack. [6][7][8][9][10] Results are disappointing in the treatment of secondary progressive multiple sclerosis (MS) as only IFN-b was shown to reduce the progression if administered to patients with a residual inflammatory component. 11,12 No medication currently approved for adults with RRMS has completed testing for pediatric MS in randomized placebo-controlled trials, although several pediatric MS trials have recently been launched. Use of DMT in pediatric MS remains off-label in many countries, especially in patients younger than 12 years; nevertheless, these medications are widely used.The high frequency of relapses in pediatric MS, especially in the first years, with a relapse rate higher than that of adults, and the pattern of MRI lesions, with more pronounced inflammatory aspects, support the use of DMT in the pediatric population as they mainly target the inflammatory component. 1,3 Recent volumetric MRI data have demonstrated that pediatric patients with MS have a smaller overall brain volume than would be expected for age, 13 in spite of the purported higher capability to compensate for brain damage, 14 suggesting that demyelinating lesions can also affect overall brain growth and development. It is also important to note that cognitive dysfunction occurs in about 1/3 of children and adolescents with MS. These findings additionally support the view that ped...

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Pediatric multiple sclerosis

et al. 2016

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“…Randomized controlled trials in pediatric MS have been very rare (Unkel et al., ), but are becomming more common now (Rose & Müller, ). We consider a randomized controlled trial assessing efficacy and safety of interferon beta‐1a compared to no treatment in pediatric MS reported by Pakdaman, Fallah, Sahraian, Pakdaman, and Meysamie (). In this trial, 16 patients were randomized to verum or control.…”

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Semi‐parametric analysis of overdispersed count and metric data with varying follow‐up times: Asymptotic theory and small sample approximations

Konietschke

Friede

Pauly³

2018

Biometrical J

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Count data are common endpoints in clinical trials, for example magnetic resonance imaging lesion counts in multiple sclerosis. They often exhibit high levels of overdispersion, that is variances are larger than the means. Inference is regularly based on negative binomial regression along with maximum‐likelihood estimators. Although this approach can account for heterogeneity it postulates a common overdispersion parameter across groups. Such parametric assumptions are usually difficult to verify, especially in small trials. Therefore, novel procedures that are based on asymptotic results for newly developed rate and variance estimators are proposed in a general framework. Moreover, in case of small samples the procedures are carried out using permutation techniques. Here, the usual assumption of exchangeability under the null hypothesis is not met due to varying follow‐up times and unequal overdispersion parameters. This problem is solved by the use of studentized permutations leading to valid inference methods for situations with (i) varying follow‐up times, (ii) different overdispersion parameters, and (iii) small sample sizes.

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“…These injectable therapies have been shown to be effective in reducing the relapse rate with a generally favorable safety profile by several observational studies [49][50][51][52] and some unblinded RCT. 53,54 In general, it is recommended to initiate interferon-beta at one-quarter of the adult-dose and increase slowly up to the full adult dose, especially for children aged 12 years and older with a bodyweight more than 30 kg. 46 As for glatiramer acetate, it can be initiated at the full adult dose.…”

Section: Treatment Of Pediatric Msmentioning

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Clinical features, diagnosis and therapeutic strategies in pediatric multiple sclerosis

Ochi

2017

Clinical & Exp Neuroim

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Multiple sclerosis (MS) is a complex immune-mediated disease characterized by recurrent demyelinating episodes of the central nervous system, which typically occurs in young adults. It is the most common disabling neurological disease of young people; however, pediatric MS, defined as onset of MS before the age of 18 years, has been increasingly recognized worldwide in the past two decades. Pediatric MS might represent up to 10% of all patients with MS. As in adults, the diagnosis of pediatric MS rests on the demonstration of dissemination of lesions in both space and time, and the exclusion of alternative diagnosis. However, it can be more difficult to distinguish MS accurately from other conditions in children compared with the adult population, because there is considerable overlapping of clinical and magnetic resonance imaging features between pediatric MS and other acquired demyelinating disorders of the central nervous system. In view of therapeutic strategies, although interferon-beta and glatiramer acetate are the most commonly used disease-modifying drugs for pediatric MS so far, none of the current available disease-modifying drugs were tested in pediatric MS by randomized controlled trials, and thus there is limited information regarding the efficacy and safety. The present review article describes the epidemiology, clinical features, consensus definition and treatment strategy of pediatric MS.

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Treatment of Early Onset Multiple Sclerosis with Suboptimal Dose of Interferon Beta-1a

Abstract: Treatment with interferon beta-1a is well tolerated for a long period of time and may be effective in substandard doses in early onset multiple sclerosis.

Cited by 38 publications

References 10 publications

Pediatric multiple sclerosis

Pediatric multiple sclerosis

Semi‐parametric analysis of overdispersed count and metric data with varying follow‐up times: Asymptotic theory and small sample approximations

Clinical features, diagnosis and therapeutic strategies in pediatric multiple sclerosis

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