Search

Introduction: Natalizumab has proved to be more effective than fingolimod in reducing disease activity in relapsing-remitting multiple sclerosis (RRMS). Whether this association is universal for all patient groups remains to be determined., Objective: The aim of this study was to compare the relative effectiveness of natalizumab and fingolimod in RRMS subgroups defined by the baseline demographic and clinical characteristics of interest., Methods: Patients with RRMS who were given natalizumab or fingolimod were identified in a merged cohort from three international registries. Efficacy outcomes were compared across subgroups based on patients' sex, age, disease duration, Expanded Disability Status Scale (EDSS) score, and disease and magnetic resonance imaging (MRI) activity 12 months prior to treatment initiation. Study endpoints were number of relapses (analyzed with weighted negative binomial generalized linear model) and 6-month confirmed disability worsening and improvement events (weighted Cox proportional hazards model), recorded during study therapy. Each patient was weighted using inverse probability of treatment weighting based on propensity score., Results: A total of 5148 patients (natalizumab 1989; fingolimod 3159) were included, with a mean ± standard deviation age at baseline of 38 ± 10 years, and the majority (72%) were women. The median on-treatment follow-up was 25 (quartiles 15-41) months. Natalizumab was associated with fewer relapses than fingolimod (incidence rate ratio [IRR]; 95% confidence interval [CI]) in women (0.76; 0.65-0.88); in those aged ≤ 38 years (0.64; 0.54-0.76); in those with disease duration ≤ 7 years (0.63; 0.53-0.76); in those with EDSS score < 4 (0.75; 0.64-0.88), < 6 (0.80; 0.70-0.91), and ≥ 6 (0.52; 0.31-0.86); and in patients with pre-baseline relapses (0.74; 0.64-0.86). A higher probability of confirmed disability improvement on natalizumab versus fingolimod (hazard ratio [HR]; 95% CI) was observed among women (1.36; 1.10-1.66); those aged > 38 years (1.34; 1.04-1.73); those with disease duration > 7 years (1.33; 1.01-1.74); those with EDSS score < 6 (1.21; 1.01-1.46) and ≥ 6 (1.93; 1.11-3.34); and patients with no new MRI lesion (1.73; 1.19-2.51)., Conclusions: Overall, in women, younger patients, those with shorter disease durations, and patients with pre-treatment relapses, natalizumab was associated with a lower frequency of multiple sclerosis relapses than fingolimod. It was also associated with an increased chance of recovery from disability among most patients, particularly women and those with no recent MRI activity., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objectives: To estimate the nationwide population-based incidence, prevalence, and geographical distribution of neuromyelitis optica (NMO) spectrum disorder (NMOSD) in Denmark based on the 2015 International Panel for NMO Diagnosis (IPND) criteria., Methods: We conducted a multicentre, historically prospective study. Data were sourced from the Danish National Patient Registry, the Danish Multiple Sclerosis Registry, departments of neurology, and laboratories providing aquaporin-4 antibody test. Cases were selected based on the 2006 Wingerchuk and the 2015 IPND criteria and were individually validated by an expert panel., Results: We confirmed NMO in 30 cases (2006 criteria) and NMOSD in 56 cases (2015 IPND criteria) between 2007 and 2014. Defined by the 2006 criteria, the incidence of NMO was 0.029 per 100,000 person-years (95% confidence interval [CI] 0.014-0.051), and the prevalence (aged 16 years and older) was 0.566 per 100,000 (95% CI 0.370-0.830). Based on the 2015 IPND criteria, the incidence of NMOSD was 0.070 per 100,000 person-years (95% CI 0.046-0.102), and the prevalence (aged 16 years and older) was 1.09 per 100,000 (95% CI 0.808-1.440), without regional differences., Conclusions: Our estimates of incidence and prevalence are similar to other Caucasian population-based studies using the 2015 IPND criteria. We found no geographical clustering in Denmark., (Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: The incidence of multiple sclerosis (MS) in Denmark has doubled in women since 1970, whereas it has been almost unchanged in men. The rapid epidemiological changes suggest that environmental factors may modify the risk of MS., Objectives: To investigate whether occupational, physical, or social environmental influence the risk of MS differently in women than in men., Methods: The cohort consists of all 1403 patients (939 women, 464 men) identified through Danish Multiple Sclerosis Registry aged 1-55 of years at clinical onset between 2000 and 2004, and up to 25 control persons for each case, matched by sex, year of birth and residential municipality. The same cohort was previously used to investigate the influence of the reproductive factors on the risk of MS., Results: By linkage to Danish population registers we found a slight albeit statistically significant excess for 6 female MS patients who had been employed in agriculture: OR 3.52; 95% CI 1.38-9.00, p=0.008 (0.046 when corrected for multiple significance) and a trend for exposure to outdoor work in 12 : OR 1.94, 95% CI 1.06-3.55, p=0.03 (0.09 when corrected for multiple significance), but the numbers of cases were small, and the effects were not found in men. Educational level, housing conditions in youth, or the presence of children unrelated by blood in the household did not influence the risk of MS., Conclusions: Our study did not reveal any additional factors beyond the previously published childbirths which could explain the extent of the MS incidence increase in women., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: The female preponderance in incidence of multiple sclerosis (MS) calls for investigations into sex differences in comorbidity with other autoimmune diseases (ADs)., Objectives: To determine whether male and female patients with MS have a higher frequency of autoimmune comorbidity than controls, and to describe the type and frequency of ADs that are associated with MS., Methods: Our database was established by linkage of the Danish MS Registry to The Danish National Patient Register and consisted of 1403 patients of both sexes with clinical onset of MS between 2000 and 2004, and 25 matched controls for every case., Results: None of the ADs occurred more frequently in female cases than in controls. Male cases were more likely to have Type I diabetes mellitus (odds ratio (OR) = 3.34; 95% CI 1.40 - 7.02; p < 0.008), Crohn's disease (OR = 5.03; 95% CI 1.18 - 16.10; p = 0.03) and systemic lupus erythematosus (OR = 12.55; 95% CI 1.62 - 69.95; p = 0.02) than male controls., Conclusions: Autoimmune disorders are rare, but some of them tend to occur together with MS at a higher rate than in controls. Although women are generally more prone to ADs than men, significantly increased occurrence of other ADs were only found in male MS patients., (© The Author(s) 2014.)

Background: The incidence of multiple sclerosis (MS) in Denmark has doubled in women since 1970, whereas it has been almost unchanged in men., Objectives: To investigate whether age at first childbirth and number of births have an effect on the risk of developing MS., Methods: The cohort consisted of 1403 patients with MS of both sexes, identified through the Danish Multiple Sclerosis Registry, with clinical onset between 2000 and 2004. For each case, 25 control persons were drawn by random from the Danish Civil Registration System matched by sex, year of birth, and residential municipality., Results: More female cases than controls had no childbirths or fewer births before clinical onset (p=0.018) but only in the last five years preceding onset (p<0.0001). Childbirths within five years before clinical onset reduced the risk of MS onset in women: OR=0.54 (95% CI 0.41-0.70, p<0.0001) for one child and OR=0.68 (95% CI 0.53-0.87, p=0.002) for more than one child. Parental age at first childbirth had no effect on the risk of MS., Conclusions: The data did not suggest reversed causality between childbirth and MS.

Background: Time to disability pension is one of the endpoints to be used to determine the prognosis of multiple sclerosis (MS) in prospective studies., Objective:   To assess the time to cessation of work and receiving disability pension in MS, and how it may depend on gender, type of work and age and symptom at onset., Method: A total of 2240 Danes with onset of definite/probable MS 1980-1989, identified from the Danish MS-Registry, were included. Information on social endpoints was retrieved from Statistics Denmark. Cox regression analyses were used with onset as starting point., Results: Afferent onset symptoms [hazard ratio (HR 0.57)] and non-physical type of work (HR 0.70) were favourable prognostic factors compared with high age at onset, physical work and efferent symptoms at onset. The mean time to disability pension was 13 years for patients with afferent/brainstem onset symptom but 8.7 years for those with efferent onset symptoms (P < 0.0001). The effect of onset symptom was reduced and the effect of sex became significant when all covariates and age at onset were included in multivariate Cox regression., Conclusions: Onset age, type of onset symptom and work are robust predictors of disability pension in MS. Disability pension proves to be a reliable milestone in estimation of the prognosis of MS., (© 2010 The Author(s). Journal compilation © 2010 EFNS.)

Background: There is a need for follow-up studies of the familial situation of multiple sclerosis (MS) patients., Objectives: To evaluate the probability of MS patients to remain in marriage or relationship with the same partner after onset of MS in comparison with the population., Patients and Methods: All 2538 Danes with onset of MS 1980-1989, retrieved from the Danish MS-Registry, and 50,760 matched and randomly drawn control persons were included. Information on family status was retrieved from Statistics Denmark. Cox analyses were used with onset as starting point., Results: Five years after onset, the cumulative probability of remaining in the same relationship was 86% in patients vs. 89% in controls. The probabilities continued to deviate, and at 24 years, the probability was 33% in patients vs. 53% in the control persons (p < 0.001). Among patients with young onset (< 36 years of age), those with no children had a higher risk of divorce than those having children less than 7 years (Hazard Ratio 1.51; p < 0.0001), and men had a higher risk of divorce than women (Hazard Ratio 1.33; p < 0.01)., Conclusion: MS significantly affects the probability of remaining in the same relationship compared with the background population.

Multiple sclerosis affects young and middle-aged people and often leads to physical and cognitive handicaps. There is a need for detailed knowledge of the social consequences of the disease. We aim here to describe the course of the working life and career of multiple sclerosis patients at the time of onset and thereafter, in terms of probability of early pension and income development. All 2538 patients with multiple sclerosis in Denmark with disease onset between 1980 and 1989, identified through the Danish MS-Registry, were included in this study. Twenty matched control persons per patient were randomly drawn from the civil registration system. Information on economic status was retrieved from Statistics Denmark. A survival analysis technique was used with onset as the starting point. We found that the probability of remaining without early pension was at 5 years 70% for patients and 97% for controls, and at 20 years 22% for patients and 86% for controls. Due to lower rates for early pension, gross income with time was lower in patients than controls. We conclude that multiple sclerosis seriously affects the economic life of multiple sclerosis patients, even within a few years of onset.

Background: The idea of physical trauma being involved in the causation of multiple sclerosis (MS) had been discussed since the earliest description of the illness. Despite the ongoing debate, the proposed association between physical and especially head trauma and MS failed to be proved or to be refuted conclusively., Objective: To determine whether head trauma is associated with an increased risk of developing MS., Method: A cohort of 150,868 subjects, 95,111 men, and 55,757 women registered in the National Danish Patient Registry with hospital admission for cerebral concussion, contusion, or skull fracture between 1977 and 1992, aged under 55, was selected. This trauma cohort was linked with the Danish MS Registry and followed up to the end of 1999 to retrieve subjects who had onset of MS after the year of the head trauma. We calculated the expected number of subjects, who, under a null-hypothesis, would subsequently develop MS, by using population age-, year-, and sex-specific MS-incidence densities from the Danish MS Registry., Results: For men and women combined, the observed to expected number of MS cases (possible cases included) with onset after the head injury was 182/193.6 (standardized incidence ratio [SIR], 0.94; 95% CI, 0.81-1.09) and for possible MS excluded, 171/164.7 (SIR, 1.04; 95% CI, 0.89-1.21). In an analysis of a sub-cohort of 16,425 subjects with severe trauma (contusion, traumatic cerebral hemorrhage, and base or skull fracture), the observed to expected numbers, including possible MS, were 15/15.3 (SIR, 0.98; 95% CI, 0.55-1.62) and with possible MS excluded, 13/12.9 (SIR, 1.01; 95% CI, 0.53-1.73). As for the total group and for any of the subgroups and for men and women separately, none of the SIRs differed statistically significantly from unity. Neither were there any trends, which could be missed by type II errors., Conclusion: Head injury of any severity does not affect the risk of acquiring MS later in life.