The Natural History of Multiple Sclerosis: A Geographically Based Study

Weinshenker, Brian G.; Bass, B.; Rice, George P.; Noseworthy, John H.; Carriere, W.; Baskerville, J.; Ebers, G. C.

doi:10.1093/brain/112.6.1419

Cited by 693 publications

(478 citation statements)

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“…RRMS is the most common MS subtype that includes Ϸ85% of the patients at initial presentation. The secondary progressive pattern is known to follow RRMS in Ϸ50% of the cases after 10 years of disease activity (18,19). Thus, these two subtypes might be considered as a continuous process starting with a common pathophysiological origin.…”

Section: Discussionmentioning

confidence: 99%

Antibodies to native myelin oligodendrocyte glycoprotein are serologic markers of early inflammation in multiple sclerosis

Lalive

Menge

Delarasse

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

158

113

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Myelin oligodendrocyte glycoprotein (MOG) is an integral membrane protein expressed in CNS oligodendrocytes and outermost myelin lamellae. Anti-MOG Abs cause myelin destruction (demyelination) in animal models of multiple sclerosis (MS); however, such pathogenic Abs have not yet been characterized in humans. Here, a method that specifically detects IgG binding to human MOG in its native, membrane-embedded conformation on MOG-transfected mammalian cells was used to evaluate the significance of these auto Abs. Compared with healthy controls, native MOGspecific IgGs were most frequently found in serum of clinically isolated syndromes (P < 0.001) and relapsing-remitting MS (P < 0.01), only marginally in secondary progressive MS (P < 0.05), and not at all in primary progressive MS. We demonstrate that epitopes exposed in this cell-based assay are different from those exposed on the refolded, extracellular domain of human recombinant MOG tested by solid-phase ELISA. In marmoset monkeys induced to develop MS-like CNS inflammatory demyelination, IgG reactivity against the native membrane-bound MOG is always detected before clinical onset of disease (P < 0.0001), unlike that against other myelin constituents. We conclude that (i) epitopes displayed on native, glycosylated MOG expressed in vivo are early targets for pathogenic Abs; (ii) these Abs, which are not detected in solidphase assays, might be the ones to play a pathogenic role in early MS with predominant inflammatory activity; and (iii) the cell-based assay provides a practical serologic marker for early detection of CNS autoimmune demyelination including its preclinical stage at least in the primate MS model. allergic encephalomyelitis ͉ autoimmunity ͉ clinically isolated syndrome ͉ demyelination

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Section: Discussionmentioning

confidence: 99%

Antibodies to native myelin oligodendrocyte glycoprotein are serologic markers of early inflammation in multiple sclerosis

Lalive

Menge

Delarasse

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

158

113

View full text Add to dashboard Cite

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“…However, the increased time to reach the milestone of requiring aid to walk 100 m in women has been found to be restricted to adult-onset MS and was not present in late-onset MS, when the incidence of progressive disease onset increases [38]. This MS subtype, which starts with slowly progressive neurological symptoms, is widely recognized to be predictive of a shorter time to reach the milestones of progression in MS than the MS subtype which starts with relapses [19,21,39,40]. …”

Section: Female Gender In Ms: Ms Risk Versus Progression From Onsetmentioning

confidence: 99%

Female Gender and Reproductive Factors Affecting Risk, Relapses and Progression in Multiple Sclerosis

D’hooghe

D’Hooghe²,

Keyser

2013

Gynecol Obstet Invest

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Multiple sclerosis (MS), a chronic inflammatory demyelina-ting and degenerative disease of the central nervous system, is a frequent cause of neurological disability in young adults. Female predominance has increased over the last decades. Although female gender carries a higher risk of developing relapsing remitting MS, being female and at child-bearing age also appears to provide some protection against cognitive decline and against progressive onset MS, an adverse predictive factor when considering long-term disability in MS. The risk of MS in women has been associated with an earlier age at menarche. In most studies, parity did not impact MS risk. However, the recently published association of higher parity and offspring number with a reduced risk of a first demyelinating event suggests a potential suppressive effect. Pregnancy in MS patients has been associated with a reduced relapse rate and a reduction of neurological symptoms, especially in the third trimester. Despite the increased relapse risk in the postpartum period, there is no indication of an adverse effect of childbirth on the long-term course of MS. Fertility treatment in MS has been associated with an increased relapse risk in the following 3-month period, especially when the procedure did not result in pregnancy and gonadotrophin-releasing hormone agonists were used. Altogether, there is substantial evidence to support a regulatory role of sex steroid hormones in MS. In the absence of correlations with single hormone blood levels, we can only speculate about the underlying mechanisms. In conclusion, the increased MS risk in women and the changes in relapse and progression risk in association with reproductive events suggest significant and complex interactions between immune, neuroendocrine and reproductive systems in MS.

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“…Per questi motivi, pur con le approssimazioni derivanti dalla schematizzazione di un quadro clinico assai complesso, l'evoluzione della malattia può essere valutata, nel modello di Markov, utilizzando tre matrici di transizione, che forniscono: la probabilità di progressione di disabilità nella forma SMRR, la probabilità di conversione da una forma SMRR alla forma SMSP e la probabilità di progressione di disabilità nella forma SMSP. Le probabilità usate per descrivere la storia naturale della malattia sono state desunte dal database London Ontario, uno dei registri osservazionali più completi e duraturi su pazienti affetti da sclerosi multipla, che ha raccolto informazioni longitudinalmente tra il 1972 e il 2000 [23][24][25]. Per quanto riguarda le ricadute, i tassi per paziente/anno in assenza di trattamento, sono stati ricavati dagli studi registrativi di dimetil-fumarato [15,16], che documentano la frequenza annuale di accadimento, nei 12 mesi precedenti all'ingresso negli studi clinici, per i pazienti con EDSS ≤ 5.…”

Section: Storia Naturale Della Malattiaunclassified

[Cost-effectiveness analysis of delayed-release dimethyl-fumarate in the treatment of relapsing-remitting multiple sclerosis in Italy]

Furneri¹,

Santoni

Marchesi

et al. 2016

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multipla recidivante-remittente (SMRR). Le terapie iniettive di prima linea (interferoni -IFN beta-1a, IFN beta-1b e glatiramer acetato -GA), si sono dimostrate variamente efficaci nel determinare un miglioramento IntroduzIone e obIettIvI dell'analIsINegli ultimi decenni, il trattamento con terapie disease-modifying (DMT) ha permesso di modificare la storia naturale della sclerosi METHODS: The analysis was conducted from the perspective of the Italian National Healthcare Service (NHS) and outcomes and costs were evaluated over a 50-year time horizon (equivalent to a lifetime horizon). Both outcomes and costs were discounted at 3.5%. The Markov model estimates the clinical and economic consequences of treating RRMS patients with the following therapeutic options: DMF, interferon (IFN) beta-1a intramuscular (IM); IFN beta-1a subcutaneous (SC) at two different doses, 22 mcg and 44 mcg; IFN beta-1b SC; glatiramer acetate (GA) SC 20 mg; oral teriflunomide. Clinical efficacy data used in this analysis came from an elaboration of the mixed treatment comparison (MTC) already published. According to the Italian NHS perspective, only the following direct costs were considered: pharmacological treatment acquisition, treatment monitoring, relapse management, direct costs associated with disability, adverse event management. Administration costs were assumed equal to €0, because every treatment included in the economic analysis can be self-administered. One-way and probabilistic sensitivity analyses were developed and cost effectiveness acceptability curves generated. RESULTS: In the base-case analysis, DMF was more efficacious than alternatives, in terms of both survival (19.496 vs. 19.297-19.461 discounted LYs, respectively), and QALYs (6.548 vs. 5.172-6.212 discounted QALYs, respectively). Per-patient lifetime costs with DMF amounted to € 276,500, similarly to the other options. DMF was the drug with the largest effect of disability cost reduction. DMF was dominant vs. IFN beta-1a 44 mcg and cost-effective vs. all other IFNs, GA and teriflunomide, with incremental cost-effectiveness ratio (ICERs) between € 11,272 and € 23,409. All ICER values were lower than the € 50,000 per QALY threshold. One-way sensitivity analysis showed that, for all tested scenarios, ICER of DMF vs. therapeutic alternatives remained favourable (≤ 50.000 €/QALY gained) and the results of probabilistic sensitivity analysis showed that the probability for DMF of being favourable (≤ 50.000 €/QALY gained) was between around 70% and 93%, thus ensuring robustness of the results. CON-CLUSIONS: The results of this economic analysis show that, at the current price and the described assumptions, DMF represents a cost-effective option vs. other available first-line treatments indicated in RRMS in the perspective of the Italian NHS.

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The Natural History of Multiple Sclerosis: A Geographically Based Study

Cited by 693 publications

References 0 publications

Antibodies to native myelin oligodendrocyte glycoprotein are serologic markers of early inflammation in multiple sclerosis

Antibodies to native myelin oligodendrocyte glycoprotein are serologic markers of early inflammation in multiple sclerosis

Female Gender and Reproductive Factors Affecting Risk, Relapses and Progression in Multiple Sclerosis

[Cost-effectiveness analysis of delayed-release dimethyl-fumarate in the treatment of relapsing-remitting multiple sclerosis in Italy]

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