Real‐life impact of early interferonβ therapy in relapsing multiple sclerosis

Trojano, María; Pellegrini, Fabio; Paolicelli, Damiano; Fuiani, Aurora; Zimatore, Giovanni Bosco; Tortorella, Carla; Simone, I. L.; Patti, Francesco; Ghezzi, Angelo; Zipoli, Valentina; Rossi, Paolo; Pozzilli, Carlo; Salemi, Giuseppe; Lugaresi, Alessandra; Bergamaschi, Roberto; Millefiorini, Enrico; Clerico, Marinella; Lus, Giacomo; Vianello, Marika; Avolio, Carlo; Cavalla, Paola; Lepore, Vito; Livrea, Paolo; Comi, Giancarlo; Amato, Maria Pia

doi:10.1002/ana.21757

Cited by 136 publications

(120 citation statements)

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“…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.…”

Section: Introductionmentioning

confidence: 99%

“…Taken together, these data indicate that it is appropriate to intervene early to prevent disease progression. The adult-onset MS experience suggests that DMTs are more effective if administered early in relapsing MS. 4,5 CURRENT VIEWS OF FIRST-LINE TREATMENT IN PEDIATRIC MS The efficacy and safety of IFN-b and GA in pediatric MS has been assessed by several phase 4 observational studies whereas comparable information is not currently available on the use of teriflunomide, dimethyl fumarate, and fingolimod. Pediatric trials with these agents are ongoing and their use in children with MS should generally occur in the context of controlled clinical trials, or considered with extreme caution in selected cases, until data on their effectiveness, tolerability, and safety are available.…”

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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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Section: Introductionmentioning

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Pediatric multiple sclerosis

et al. 2016

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“…This genetic knowledge should also be translated to develop clinically useful biomarkers [4] aimed at the key questions of when to start treatment (and in whom), which drug to select (from several now available) and when to change. Despite knowledge that early effective treatment for autoimmune disease can be critical in delaying progression [5] and individuals respond to some therapies better than others, practical biomarkers have not yet been identified to guide clinical management of MS.…”

Section: Introductionmentioning

confidence: 99%

The low EOMES/TBX21 molecular phenotype in multiple sclerosis reflects CD56+ cell dysregulation and is affected by immunomodulatory therapies

McKay

Gatt

Fewings

et al. 2016

Clinical Immunology

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Multiple Sclerosis (MS) is an autoimmune disease treated by therapies targeting peripheral blood cells. We previously identified that expression of two MS-risk genes, the transcription factors EOMES and TBX21 (ET), was low in blood from MS and stable over time. Here we replicated the low ET expression in a new MS cohort (p<0.0007 for EOMES, p < 0.028 for TBX21) and demonstrate longitudinal stability (p<10 -4 ) and high heritability (h 2 =0.48 for EOMES) for this molecular phenotype. Genes whose expression correlated with ET, especially those controlling cell migration, further defined the phenotype. CD56+ cells and other subsets expressed lower levels of Eomes or T-bet protein and/or were underrepresented in MS. EOMES and TBX21 risk SNP genotypes, and serum EBNA-1 titres were not correlated with ET expression, but HLA-DRB1*1501 genotype was. ET expression was normalised to healthy control levels with natalizumab, and was highly variable for glatiramer acetate, fingolimod, interferon-beta, dimethyl fumarate.

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“…In this context, monitoring of therapeutic responses to immunomodulators is critical for the patient, who now lives in an era of therapeutic strategies and resources that have been available for less than two decades. The knowledge of the biological aspects of MS allows us to establish therapeutic windows of nonresponders to early intervention 8 . Finding nonresponders within the population in treatment is an ongoing challenge that requires the Expanded Disability Status Scale (EDSS) score at each visit, the monitoring of new lesions on MRI each year and the number of relapses in each period.…”

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confidence: 99%

Clinical response to interferon beta and glatiramer acetate in multiple sclerosis patients: a Brazilian cohort

Pereira

Malfetano

Meira

et al. 2012

Arq. Neuro-Psiquiatr.

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INTRODUCTION: Many patients with multiple sclerosis (MS) are currently receiving treatment with interferon beta (IFNb) and glatiramer acetate (GA). Identifying nonresponders patients is important to define therapy strategies. Several criteria for treatment response to IFNb and GA have been proposed. OBJECTIVE: It was to investigate the response to treatment with IFNb-1a, IFNb-1b and GA among relapsing-remitting multiple sclerosis (RRMS) patients. METHODS: We analyzed treatment response to IFNb and GA in ninety-one RRMS patients followed for at least one year. Clinical response was established by clinical criteria based on relapses, disability progression or both. RESULTS: We observed a proportion of nonresponders, ranging from 3.3 to 42.9%, depending on the stringency of the criteria used. CONCLUSIONS: Our sample of Brazilian patients with MS has similarities when compared to other studies and there was no statistically significant difference regarding age, gender, ethnicity or disease duration between responders and nonresponders.

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Real‐life impact of early interferonβ therapy in relapsing multiple sclerosis

Abstract: Greater benefits on disability progression may be obtained by an early IFNbeta treatment in RRMS.

Cited by 136 publications

References 39 publications

Pediatric multiple sclerosis

Pediatric multiple sclerosis

The low EOMES/TBX21 molecular phenotype in multiple sclerosis reflects CD56+ cell dysregulation and is affected by immunomodulatory therapies

Clinical response to interferon beta and glatiramer acetate in multiple sclerosis patients: a Brazilian cohort

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