Initial treatment strategy and clinical outcomes in Finnish MS patients : a propensity-matched study

Background The optimal treatment strategy with disease-modifying therapies (DMTs) in relapsing-remitting multiple sclerosis (RRMS) remains uncertain. Objective To compare outcomes of initial treatment with infusion therapies and starting therapy with medium efficacy therapy in a propensity-matched cohort of Finnish RRMS patients. Methods A total of 154 RRMS patients initiating natalizumab, alemtuzumab, ocrelizumab or rituximab as first DMT (high efficacy DMT, heDMT group) and 1771 patients initially treated with injectable therapies, teriflunomide or dimethylfumarate and escalated based on disease activity (moderate efficacy DMT, meDMT group) were identified from the Finnish MS registry. Nearest neighbor propensity matching (1:1, caliper 0.1) was performed for age, sex, baseline Expanded Disability Status Scale (EDSS), annual relapse rate (ARR) one year prior DMT and time since MS symptom onset. Primary outcome was time to 6-month confirmed EDSS progression and the secondary outcome time to first relapse. Results In the propensity-matched group comparisons, the probability of 6-month confirmed disability progression (CDP) at 5 years after DMT start was 28.4% (95% CI 15.7-39.3) in the heDMT group (n = 66) and 47.0% (95% CI 33.1-58.1) in meDMT group (n = 66), p = 0.013. Probability of relapse at 5 years was 34.6% (95% CI 24.1-43.6) for heDMT (n = 105) and 47.2% (95% CI 36.6-56.1) for meDMT (n = 105), p = 0.019. Conclusions Initiating MS-therapy with heDMT significantly reduced the risk of 5-year disability progression and relapse compared to using meDMT as first DMT choice in propensity-matched groups of Finnish MS-patients.Peer reviewe

Multiple sclerosis epidemiology in Finland: regional differences and high incidence

OBJECTIVES: Studies on the east-west gradient of multiple sclerosis (MS) are scarce. In Finland, epidemiological differences have been only partially elucidated, but the MS risk is high, and it has been claimed that the occurrence follows a longitudinal gradient. In this register-based study, we updated the MS epidemiology in southwest Finland (SwF) and compared it to the easternmost hospital district, North Karelia (NK), for which no previous data exist.MATERIAL AND METHODS: Patients with ICD-10 code G35 were identified from hospital district administrative data. Patient records were reviewed to include only cases with a definitive diagnosis. Incidence period covered 5 years (2012-2016) and the prevalence date was December 31, 2016. Results were standardized using the direct method.RESULTS: 1184 persons had MS in SwF and 253 persons in NK at the end of 2016. The prevalence was 280/100,000 (95% Cl 264-296) in SwF and 168/100,000 (95% Cl 148-190) in NK (age-standardized for the European standard population 2013). During the incidence period, 211 new MS diagnoses were made in SwF and 49 in NK. The annual age-standardized (ESP 2013) incidence was 12.1/100,000 person-years (95% Cl 10.5-13.8) in SwF and 8.6/100,000 person-years (95% Cl 6.4-11.2) in NK in the age group 10-69 years.CONCLUSIONS: There are regional differences in MS epidemiology in Finland, possibly related to demographic, social and genetic circumstances but the retrospective nature and limited sample size of this study might introduce some uncertainty to the calculations. SwF is a region with a globally very high risk for MS. This article is protected by copyright. All rights reserved.</p

Admission sodium level and prognosis in adult Guillain-Barré syndrome

PURPOSE: Guillain-Barré syndrome (GBS) varies in severity and outcome. Hyponatremia predicts poor outcome but previous studies have used divergent methodology and (pseudo)hyponatremia caused by intravenous immunoglobulin administration may confound analysis. We studied if the plasma sodium level at admission was associated with GBS outcome.METHODS: All 69 patients at least 16 years of age treated for GBS in Turku University Hospital in 2004-2013 were included in the study. Clinical information was obtained from patient charts.RESULTS: Women had lower sodium levels at admission (138; IQR 135, 140) compared to men (140; IQR 138, 142; p = 0.0116) but no association of sodium levels with demographics, pre-hospital variables or basic GBS characteristics was found. Multivariate analyses showed lower admission sodium levels to be associated with worse functional status at one year from disease onset (OR 1.37; 95% CI 1.07-1.76; p = 0.0136) and probability of being discharged to another care facility from the hospital (OR 1.31; 95% CI 1.05-1.64; p = 0.0180) but not associated with need of intensive care unit care (p = 0.09) or mechanical ventilation (p = 0.45), length of hospital stay (p =0.48) or functional status at six months (p = 0.07).CONCLUSIONS: Low plasma sodium level at admission is associated with a more severe disease course and a worse outcome in GBS independently of previously identified prognostic factors. Hyponatremia does not, however, appear to be caused by disease-specific factors.</div

Initial treatment strategy and clinical outcomes in Finnish MS patients: a propensity-matched study

BackgroundThe optimal treatment strategy with disease-modifying therapies (DMTs) in relapsing–remitting multiple sclerosis (RRMS) remains uncertain.ObjectiveTo compare outcomes of initial treatment with infusion therapies and starting therapy with medium efficacy therapy in a propensity-matched cohort of Finnish RRMS patients.MethodsA total of 154 RRMS patients initiating natalizumab, alemtuzumab, ocrelizumab or rituximab as first DMT (high efficacy DMT, heDMT group) and 1771 patients initially treated with injectable therapies, teriflunomide or dimethylfumarate and escalated based on disease activity (moderate efficacy DMT, meDMT group) were identified from the Finnish MS registry. Nearest neighbor propensity matching (1:1, caliper 0.1) was performed for age, sex, baseline Expanded Disability Status Scale (EDSS), annual relapse rate (ARR) one year prior DMT and time since MS symptom onset. Primary outcome was time to 6-month confirmed EDSS progression and the secondary outcome time to first relapse.ResultsIn the propensity-matched group comparisons, the probability of 6-month confirmed disability progression (CDP) at 5 years after DMT start was 28.4% (95% CI 15.7–39.3) in the heDMT group (n = 66) and 47.0% (95% CI 33.1–58.1) in meDMT group (n = 66), p = 0.013. Probability of relapse at 5 years was 34.6% (95% CI 24.1–43.6) for heDMT (n = 105) and 47.2% (95% CI 36.6–56.1) for meDMT (n = 105), p = 0.019.ConclusionsInitiating MS-therapy with heDMT significantly reduced the risk of 5-year disability progression and relapse compared to using meDMT as first DMT choice in propensity-matched groups of Finnish MS-patients.</p

Thalamic Atrophy Without Whole Brain Atrophy Is Associated With Absence of 2-Year NEDA in Multiple Sclerosis

Purpose: To study which brain volume measures best differentiate early relapsing MS (RMS) and secondary progressive MS (SPMS) patients and correlate with disability and cognition. To test whether isolated thalamic atrophy at study baseline correlates with NEDA (no evidence of disease activity) at 2 years.Methods: Total and regional brain volumes were measured from 24 newly diagnosed RMS patients 6 months after initiation of therapy and 2 years thereafter, and in 36 SPMS patients. Volumes were measured by SIENAX and cNeuro. The patients were divided into subgroups based on whole brain parenchyma (BP) and thalamic atrophy at baseline. Standard scores (z-scores) were computed by comparing individual brain volumes against healthy controls. A z-score cut-off of - 1.96 was applied to separate atrophic from normal brain volumes. The Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT) were assessed at baseline and at 2 years. Differences in achieving NEDA-3, NEDA-4, EDSS progression, and SDMT change were analyzed between patients with no thalamic or BP atrophy and in patients with isolated thalamic atrophy at baseline.Results: At baseline, 7 SPMS and 12 RMS patients had no brain atrophy, 8 SPMS and 10 RMS patients had isolated thalamic atrophy and 2 RMS and 20 SPMS patients had both BP and thalamic atrophy. NEDA-3 was reached in 11/19 patients with no brain atrophy but only in 2/16 patients with isolated thalamic atrophy (p = 0.012). NEDA-4 was reached in 7/19 patients with no brain atrophy and in 1/16 of the patients with isolated thalamic atrophy (p = 0.047). At 2 years, EDSS was same or better in 16/19 patients with no brain atrophy but only in 5/17 patients with isolated thalamic atrophy (p = 0.002). There was no significant difference in the EDSS, relapses or SDMT between patients with isolated thalamic atrophy and no atrophy at baseline.Conclusion: Patients with isolated thalamic atrophy were at a higher risk for not reaching 2-year NEDA-3 and for EDSS increase than patients with no identified brain atrophy. The groups were clinically indistinguishable. A single measurement of thalamic and whole brain atrophy could help identify patients needing most effective therapies from early on

Multiple sclerosis in Finland 2018-Data from the national register

Objectives Finland is a high-risk multiple sclerosis (MS) region, but a national MS register has not existed until 2014. In this paper, we present the Finnish MS register variables and data collected by 31 December 2018. Materials and Methods Numbers and data counts of MS patients in the register (ICD-10 code G35) are presented. The disease types and proportion of patients receiving disease-modifying treatments (DMTs) were analysed in five hospital districts with most complete data sets. MS prevalence in Finland was estimated using administrative hospital discharge data as an additional resource. Results There were a total of 8722 MS patients in the Finnish MS register by 31 December 2018 (71.5% females). Mean age at MS diagnosis was 38.7 years and peak prevalence was at age 50-54 years. Disease course was relapsing remitting (RRMS) in 66.7%, secondary progressive (SPMS) in 13.5%, and primary progressive (PPMS) in 7.9% of the 5365 MS patients in the selected districts with most complete data. A total of 66.0% of RRMS patients, 19.6% of SPMS patients and 9.9% of PPMS patients were receiving DMTs. By combining MS register data with databases of those hospitals that had not joined the register, the nationwide prevalence estimate was between 10 and 11 thousand patients (corresponding to crude prevalence 180-200/100 000). Conclusions The Finnish MS register is currently used in 15/21 Finnish hospital districts. By register integration into the electronic patient files, the coverage of the register has increased to approximately 80% of the estimated Finnish MS population.Peer reviewe

Aivojen magneettikuvaus MS-taudin immunologisen hoidon seurannassa

Aivojen magneettikuvaus (MK) osoittaa MS-taudin aktiivisuuden herkemmin kuin kliiniset relapsit, minkä vuoksi hoidossa käytettävän immunologisen hoitovasteen arvion tulee perustua kliiniseen taudinkuvaan ja aivojen kuvantamiseen. MK-seurantaan tarvitaan T2-, flair- ja T1-painotteiset kuvat, gadolinium-tehostaminen ja atrofian arviointi. Ensilinjan immunologisessa hoidossa ensimmäinen MK otetaan 6-12 kuukauden kuluttua lääkehoidon aloituksesta. Jos silloin havaitaan uusia muutoksia, seuraava kuvantaminen tehdään 1-2 vuoden kuluttua. Huonoa hoitovastetta vaikuttaa kuvaavan se, jos 6-12 kuukauden kuluttua hoidon aloituksessa tehdyssä magneettikuvassa esiintyy uusia (yli 4) tai kasvavia T2-painotteisia tulehduspesäkkeitä. Huonosta hoitovasteesta kertoo myös gadoliniumilla tehostuvien muutosten esiintyminen seurannan aikana. Tällöin suositellaan hoidon tehostamista, vaikka pahenemisvaiheita ei olisi esiintynyt. Fingolimodihoidossa seurantakuvaukset tehdään 6-12 kuukauden kuluttua hoidon aloituksesta ja 1-2 vuoden kuluttua tämän jälkeen. Alemtutsumabi- ja natalitsumabihoidossa kuvaukset ajoitetaan vuoden ja kahden vuoden päähän hoidon aloituksesta

Correlation of Circulating Omentin-1 with Bone Mineral Density in Multiple Sclerosis: The Crosstalk between Bone and Adipose Tissue

BACKGROUND: Patients with multiple sclerosis (MS) are at increased risk of osteoporosis and fractures. Adipose tissue-derived adipokines may play important roles in the osteoimmunology of MS. In order to determine whether omentin-1 and vaspin may be related to bone health in MS patients, we compared circulating levels of these recently identified adipokines, between MS patients and healthy controls. METHODS: A total of 35 ambulatory MS patients with relapsing-remitting courses were compared with 38 age- and sex-matched healthy controls. Bone mineral density (BMD) was determined for the lumbar spine (L2-L4) and the proximal femur using dual-energy x-ray absorptiometry. Circulating omentin-1, vaspin, osteocalcin, osteopontin, osteoprotegerin, the receptor activator of nuclear factor-κB ligand, matrix metalloproteinase 9, C-reactive protein and 25-hydroxy vitamin D levels were evaluated by highly specific enzyme-linked immunosorbent assay methods. RESULTS: There was no significant difference between the two groups regarding bone-related cytokines, adipocytokines, and the BMD measurements of patients with MS and the healthy controls. However, in multiple regression analysis, serum omentin-1 levels were positively correlated with BMD at the femoral neck (β = 0.49, p = 0.016), total hip (β = 0.42, p = 0.035), osteopontin (β = 0.42, p = 0.030) and osteocalcin (β = 0.53, p = 0.004) in MS patients. No correlations were found between vaspin, biochemical, and BMD measures in both groups. CONCLUSIONS: Elevated omentin-1 serum levels are correlated with BMD at the femoral neck and the serum levels of osteocalcin and osteopontin in MS patients. Therefore, there is crosstalk between adipose tissue and bone in MS

Efficacy of Vitamin D Supplementation in Multiple Sclerosis (EVIDIMS Trial): study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Multiple sclerosis is the most common chronic inflammatory disease of the central nervous system in young adults. Despite the fact that numerous lines of evidence link both the risk of disease development and the disease course to the serum level of 25-hydroxyvitamin D it still remains elusive whether multiple sclerosis patients benefit from boosting the serum level of 25-hydroxyvitamin D, mainly because interventional clinical trials that directly address the therapeutic effects of vitamin D in multiple sclerosis are sparse. We here present the protocol of an interventional clinical phase II study to test the hypothesis, that high-dose vitamin D supplementation of multiple sclerosis patients is safe and superior to low-dose supplementation with respect to beneficial therapeutic effects.</p> <p>Methods/Design</p> <p>The EVIDIMS trial is a German multi-center, stratified, randomized, controlled and double-blind clinical phase II pilot study. Eighty patients with the diagnosis of definite multiple sclerosis or clinically isolated syndrome who are on a stable immunomodulatory treatment with interferon-β1b will be randomized to additionally receive either high-dose (average daily dose 10.200 IU) or low-dose (average daily dose 200 IU) cholecalciferol for a total period of 18 months. The primary outcome measure is the number of new lesions detected on T2-weighted cranial MRI at 3 tesla. Secondary endpoints include additional magnetic resonance imaging and optical coherence tomography parameters for neuroinflammation and -degeneration, clinical parameters for disease activity, as well as cognition, fatigue, depression, and quality of life. Safety and tolerability of high-dose vitamin D supplementation are further outcome parameters.</p> <p>Discussion</p> <p>In light of the discrepancy between existing epidemiological and preclinical data on the one hand and available clinical data on the other the EVIDIMS trial will substantially contribute to the evaluation of the efficacy of high-dose vitamin D supplementation in MS patients. The study design presented here fulfills the criteria of a high-quality clinical phase II trial in MS.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01440062">NCT01440062</a></p

Proportion and characteristics of secondary progressive multiple sclerosis in five European registries using objective classifiers

Background: To assign a course of secondary progressive multiple sclerosis (MS) (SPMS) may be difficult and the proportion of persons with SPMS varies between reports. An objective method for disease course classification may give a better estimation of the relative proportions of relapsing-remitting MS (RRMS) and SPMS and may identify situations where SPMS is under reported.Materials and methods: Data were obtained for 61,900 MS patients from MS registries in the Czech Republic, Denmark, Germany, Sweden, and the United Kingdom (UK), including date of birth, sex, SP conversion year, visits with an Expanded Disability Status Scale (EDSS) score, MS onset and diagnosis date, relapses, and disease-modifying treatment (DMT) use. We included RRMS or SPMS patients with at least one visit between January 2017 and December 2019 if ≥ 18 years of age. We applied three objective methods: A set of SPMS clinical trial inclusion criteria ("EXPAND criteria") modified for a real-world evidence setting, a modified version of the MSBase algorithm, and a decision tree-based algorithm recently published.Results: The clinically assigned proportion of SPMS varied from 8.7% (Czechia) to 34.3% (UK). Objective classifiers estimated the proportion of SPMS from 15.1% (Germany by the EXPAND criteria) to 58.0% (UK by the decision tree method). Due to different requirements of number of EDSS scores, classifiers varied in the proportion they were able to classify; from 18% (UK by the MSBase algorithm) to 100% (the decision tree algorithm for all registries). Objectively classified SPMS patients were older, converted to SPMS later, had higher EDSS at index date and higher EDSS at conversion. More objectively classified SPMS were on DMTs compared to the clinically assigned.Conclusion: SPMS appears to be systematically underdiagnosed in MS registries. Reclassified patients were more commonly on DMTs.</p