V. Jokubaitis

The effect of disease-modifying treatments on conversion to secondary progressive multiple sclerosis

Patients suffering from multiple sclerosis (MS) are increasing in developed countries. Considering the physical and socioeconomical burden of MS, the cause for the increasing trend should be intensively investigated. Of note, the trend of increasing incidence of MS is most obvious in Japan, referring to a government report on the registered cases of MS. Although only 1000 patients with MS or neuromyelitis optica (NMO) were registered in 1980, there are currently more than 20,000 patients with MS/ NMO. The increase is more significant in MS than NMO, resulting in an increase in MS/NMO ratio. Regional epidemiological survey in Tokachi, Hokkaido (Houzen et al.) indicates that the increase is the reality, and not due to better awareness of the disease, improved health care system or better medical facilities. Among environmental risk factors for MS, cigarette smoking, lower exposure to sunlight, EB virus infection, or higher salt taking could not explain the increase. In the symposium, I discuss that westernization and changes in diet may at least partly explain the increase of patients with MS in Japan, possibly via altering gut microbiota and immune regulatory network.

028 Treating progressive multiple sclerosis

Introduction We showed that the available immunotherapies do not modify disability outcomes when used in secondary progressive multiple sclerosis. However, these therapies are effective in advanced active multiple sclerosis. Primary progressive multiple sclerosis may present with or without superimposed relapses. Significance of these relapses for disability accumulation and treatment remains contested. We aimed to examine the effect of the available immunotherapies in primary progressive multiple sclerosis. Methods 1427 eligible patients with primary progressive multiple sclerosis from MSBase were studied. Confirmed disability progression of disability was compared between treated and untreated propensity score-matched cohorts. Multivariable regression models were used to compare disability accrual between primary progressive multiple sclerosis with and without superimposed relapses. Finally, the effect of therapy on disability accrual in cohorts with and without superimposed relapses was analysed. Results 173 treated and 373 untreated patients were matched. No differences in the risk of disability progression (p=0.79) and improvement (p=0.98) were observed over the median 3u2009year follow-up. The likelihood of disability progression was relatively lower in patients with superimposed relapses (hazard ratio=0.83, p<0.01). We observed an association between the proportion of time on immunotherapy and the hazard of disability progression in active (hazard ratio=0.96, p=0.01) but not in the inactive primary progressive disease (p=0.21). Conclusion Superimposed relapses in primary progressive multiple sclerosis represent a favourable prognostic marker, associated with slower disability accrual. This is most likely attributed to the effectiveness of immunotherapy in active primary progressive disease. Relapse activity, therefore, is a treatable modifier of disability accrual in primary progressive disease.

Genotype and phenotype in Multiple Sclerosis - potential for disease course prediction?

Purpose of reviewThis review will examine the current evidence that genetic and/or epigenetic variation may influence the multiple sclerosis (MS) clinical course, phenotype, and measures of MS severity including disability progression and relapse rate.Recent findingsThere is little evidence that MS clinical phenotype is under significant genetic control. There is increasing evidence that there may be genetic determinants of the rate of disability progression. However, studies that can analyse disability progression and take into account all the confounding variables such as treatment, clinical characteristics, and environmental factors are by necessity longitudinal, relatively small, and generally of short duration, and thus do not lend themselves to the assessment of hundreds of thousands of genetic variables obtained from GWAS. Despite this, there is recent evidence to support the association of genetic loci with relapse rate.SummaryRecent progress suggests that genetic variations could be associated with disease severity, but not MS clinical phenotype, but these findings are not definitive and await replication. Pooling of study results, application of other genomic techniques including epigenomics, and analysis of biomarkers of progression could functionally validate putative severity markers.