Malthe Faurschou Wandall-Holm

Currently, there are limited therapeutic options for patients with non-active secondary progressive multiple sclerosis. Therefore, real-world studies have investigated differences between patients with relapsing-remitting multiple sclerosis, non-active secondary progressive multiple sclerosis and active secondary progressive multiple sclerosis. Here, we explore patterns and predictors of transitioning between these phenotypes. We performed a cohort study using data from The Danish Multiple Sclerosis Registry. We included patients with a relapsing-remitting phenotype, registered changes to secondary progressive multiple sclerosis and subsequent transitions between relapsing and non-relapsing secondary progressive multiple sclerosis, which was defined by the presence of relapses in the previous 2 years. We analysed predictors of transitioning from relapsing-remitting multiple sclerosis to relapsing and non-relapsing secondary progressive multiple sclerosis, as well as between the secondary progressive states using a multi-state Markov model. We included 4413 patients with relapsing-remitting multiple sclerosis. Within a median follow-up of 16.2 years, 962 were diagnosed with secondary progressive multiple sclerosis by their treating physician. Of these, we classified 729 as non-relapsing and 233 as relapsing secondary progressive multiple sclerosis. The risk of transitioning from relapsing-remitting to non-relapsing secondary progressive multiple sclerosis included older age (hazard ratio per increase of 1 year in age: 1.044, 95% confidence interval: 1.035–1.053), male sex (hazard ratio for female: 0.735, 95% confidence interval: 0.619–0.874), fewer relapses (hazard ratio per each additional relapse: 0.863, 95% confidence interval: 0.823–0.906), higher expanded disability status scale (hazard ratio per each additional point: 1.522, 95% confidence interval: 1.458–1.590) and longer time on disease-modifying therapies (hazard ratio per increase of 1 year in treatment, high-efficacy disease-modifying therapy: 1.095, 95% confidence interval: 1.051–1.141; hazard ratio, moderate-efficacy disease-modifying therapy: 1.073, 95% confidence interval: 1.051–1.095). We did not find significant predictors associated with the transition from relapsing secondary progressive multiple sclerosis to non-relapsing secondary progressive multiple sclerosis, whereas older age (hazard ratio per increase of 1 year in age: 0.956, 95% confidence interval: 0.942–0.971) prevented the transition from non-relapsing secondary progressive multiple sclerosis to relapsing secondary progressive multiple sclerosis. Our study suggests that transitioning from relapsing-remitting multiple sclerosis to non-relapsing secondary progressive multiple sclerosis depends on well-known factors affecting diagnosing secondary progressive multiple sclerosis. Further transitions between non-relapsing and relapsing secondary progressive multiple sclerosis are only affected by age. These findings add to the knowledge of non-active secondary progressive multiple sclerosis, a patient group with unmet needs in terms of therapies.

With rising life expectancy and advancements in disease management, we expect the multiple sclerosis population is getting older. However, evidence supporting this hypothesis remains sparse. Our study aimed to determine whether the mean age of the Danish multiple sclerosis population has increased and to analyse the developments in sex distribution, incidence, and prevalence, all of which affect age composition. We conducted a cohort study by linking nationwide data from the Danish Multiple Sclerosis Registry to the Population Statistics Registry, the Danish Cause of Death Registry, and the Historical Migration Registry. We included all living patients with a confirmed multiple sclerosis diagnosis who lived in Denmark on the 1^st of January each year from 1950 to 2023. We calculated the mean and median age, age distribution, sex distribution, incidence, and prevalence of the Danish MS population annually from 1950 to 2023. We included 28,145 individuals with multiple sclerosis. The mean age of the Danish multiple sclerosis population increased until the late 1970s to around 52.5 years, where it stabilised until 1990. The mean age experienced a slight decline to 51.2 years in 2005, followed by a subsequent rise to its peak of 54.2 years in 2023. In 1975, females comprised 58.7% of the multiple sclerosis population, increasing to 65.7% by 2000 and 68.5% in 2023. The incidence of multiple sclerosis remained stable at around 3.5 per 100,000 until 1975 and steadily increased by more than 2.5 times in 2000 to 11.4 per 100,000. Despite fluctuations, it remained relatively stable from 2000 until 2022, showing a slight decrease in 2022 compared to the previous two decades. Both overall and sex-specific prevalence exhibited an upward trend, particularly among females. Our study demonstrates that the mean age of the Danish multiple sclerosis population has increased, although not as decisively as expected. The female proportion has grown in tandem with prevalence, while incidence appears to have stabilised in recent decades after years of increase. Denmark’s robust registry data and universal healthcare system offer a unique opportunity for reliable epidemiological analysis. Our results establish a benchmark for future demographic studies in the field of multiple sclerosis.

Fingolimod is a frequently used disease-modifying therapy in relapsing–remitting multiple sclerosis. However, case reports and small observational studies indicate a highly increased risk of disease reactivation after discontinuation. We aimed to investigate the risk of radiological disease reactivation in patients discontinuing fingolimod. We performed a nationwide cohort study in Denmark, including patients who discontinued fingolimod between January 2014 and January 2023. Eligibility was a diagnosis with relapsing–remitting multiple sclerosis and two MRIs performed respectively within 1 year before and after discontinuing fingolimod. The included patients were compared with those discontinuing dimethyl fumarate with the same eligibility criteria in an unadjusted and matched propensity score analysis. Matching was done on age, sex, Expanded Disability Status Scale, MRI data, cause for treatment discontinuation, treatment duration and relapse rate. The main outcome was the presence of new T₂ lesions on the first MRI after treatment discontinuation. To identify high-risk patients among those discontinuing fingolimod, we made a predictive model assessing risk factors for obtaining new T₂ lesions. Of 1324 patients discontinuing fingolimod in the study period, 752 were eligible for inclusion [mean age (standard deviation), years, 41 (10); 552 females (73%); median Expanded Disability Status Scale (Q1–Q3), 2.5 (2.0–3.5); mean disease duration (standard deviation), years, 12 (8)]. Of 2044 patients discontinuing dimethyl fumarate in the study period, 957 were eligible for inclusion, presenting similar baseline characteristics. Among patients discontinuing fingolimod, 127 (17%) had 1–2 new T₂ lesions, and 124 (17%) had ≥3 new T₂ lesions compared with 114 (12%) and 45 (5%), respectively, for those discontinuing dimethyl fumarate, corresponding to odds ratios (95% confidence interval) of 1.8 (1.3–2.3) and 4.4 (3.1–6.3). The predictive model, including 509 of the 752 patients discontinuing fingolimod, showed a highly increased risk of new T₂ lesions among those with disease activity during fingolimod treatment and among females under 40 years. This nationwide study suggests that discontinuing fingolimod in some cases carries a risk of developing new T₂ lesions, emphasizing the importance of clinical awareness. If feasible, clinicians should prioritize the prompt initiation of new disease-modifying therapies, particularly among young females.

Microbiological etiology has been associated with surgery for infective endocarditis (IE) during admission, especially Staphylococcus aureus. We aimed to compare patient characteristics, microbiological characteristics, and outcomes by treatment choice (surgery or not). We identified patients with first-time IE between 2010 and 2020 and examined the microbiological etiology of IE according to treatment choice. To identify factors associated with surgery during initial admission, we used the Aalen–Johansen estimator and an adjusted cause-specific Cox model. One-year mortality stratified by microbiological etiology and treatment choice was assessed using unadjusted Kaplan–Meier estimates and an adjusted Cox proportional hazard model. A total of 6255 patients were included, of which 1276 (20.4%) underwent surgery during admission. Patients who underwent surgery were younger (65 vs. 74 years) and less frequently had cerebrovascular disease, cardiovascular disease, diabetes, and chronic kidney disease. Patients with Staphylococcus aureus IE were less likely to undergo surgery during admission (13.6%) compared to all other microbiological etiologies. One-year mortality according to microbiological etiology in patients who underwent surgery was 7.0%, 5.3%, 5.5%, 9.6%, 13.2, and 11.2% compared with 24.2%, 19.1%, 27,6%, 25.2%, 21%, and 16.9% in patients who received medical therapy for Staphylococcus aureus, Streptococcus spp., Enterococcus spp., coagulase-negative Staphylococci, “other microbiological etiologies”, and blood culture-negative infective endocarditis, respectively. Patients with IE who underwent surgery differed in terms of microbiology, more often having Streptococci than those who received medical therapy. Contrary to expectations, Staphylococcus aureus was more common among patients who received medical therapy only.

Introduction/objectives: Multiple sclerosis (MS) leads to physical and cognitive disability, which in turn impacts the socioeconomic status of the individual. The altered socioeconomic trajectory combined with the critical role of aging in MS progression could potentially lead to pronounced differences between MS patients and the general population. Few nations have the ability to connect long-term clinical and socioeconomic data at the individual level, and Denmark's robust population-based registries offer unique insights. This study aimed to examine the socioeconomic aspects of elderly Danish MS patients in comparison to matched controls from the general population.Methods: A nationwide population-based study in Denmark was conducted, comprising all living MS patients aged 50 years or older as of 1 January 2021. Patients were matched 1:10 based on sex, age, ethnicity, and residence with a 25% sample of the total Danish population. Demographic and clinical information was sourced from the Danish Multiple Sclerosis Registry, while socioeconomic data were derived from national population-based registries containing details on education, employment, social services, and household characteristics. Univariate comparisons between MS patients and matched controls were then carried out.Results: The study included 8,215 MS patients and 82,150 matched individuals, with a mean age of 63.4 years (SD: 8.9) and a 2:1 female-to-male ratio. For those aged 50–64 years, MS patients demonstrated lower educational attainment (high education: 28.3 vs. 34.4%, P < 0.001) and fewer received income from employment (46.0 vs. 78.9%, P < 0.001), and working individuals had a lower annual income (48,500 vs. 53,500€, P < 0.001) in comparison to the controls. Additionally, MS patients within this age group were more likely to receive publicly funded practical assistance (14.3 vs. 1.6%, P < 0.001) and personal care (10.5 vs. 0.8%, P < 0.001). Across the entire population, MS patients were more likely to live alone (38.7 vs. 33.8%, P < 0.001) and less likely to have one or more children (84.2 vs. 87.0%, P < 0.001).Conclusion: MS presents significant socioeconomic challenges among the elderly population, such as unemployment, reduced income, and increased dependence on social care. These findings underscore the pervasive impact of MS on an individual's life course, extending beyond the clinical symptoms of cognitive and physical impairment.

BackgroundInitiation of disease-modifying therapy early in the disease course of relapsing-remitting multiple sclerosis (RRMS) has demonstrated beneficial effects on clinical outcomes, but socioeconomic outcomes remain largely unexplored.ObjectiveTo investigate the association between the delay from disease onset to first treatment and the hazard of disability pension.MethodsWe performed a population-based cohort study with data from the nationwide Danish Multiple Sclerosis Registry and Danish nationwide registries. Patients with a disease onset between 1 January 1996 to 5 April 2016 were followed until disability pension or a competing risk/censoring event. 7859 patients were assessed for eligibility of which 5208 were included in the final cohort. Key inclusion criteria were: a diagnosis of multiple sclerosis, relapsing-remitting phenotype, treatment in history, age 18–65 years and an Expanded Disability Status Scale≤4. Patients were categorised according to time from onset to first treatment: within 1 year (early), between 1 and 4 years (intermediate) and from 4 to 8 years (late).ResultsOf the 5208 patients, 1922 were early, 2126 were intermediate and 1160 were late. Baseline clinical and socioeconomic variables were well balanced. The hazard of receiving disability pension increased with increasing delay of treatment initiation compared with the early group. Cox regression estimates adjusted for clinical and socioeconomic confounders: intermediate (HR, 1.37; 95% CI, 1.12 to 1.68) and late (HR, 1.97; 95% CI, 1.55 to 2.51).ConclusionEarly treatment initiation is associated with a reduced risk of disability pension in patients with RRMS. This finding underlines the importance of early diagnosis and treatment on a patient-centred, socioeconomic disability milestone.

Background: Studies have demonstrated an increasing mean age of the population with multiple sclerosis (MS). The association between increased age and socioeconomic outcomes has been investigated sparsely. Objective: The purpose of this study is to describe the demographic and socioeconomic status of the current Danish population of patients with MS according to age and to assess the age-related risks of no income or losing all income from earnings or receiving disability pension. Methods: The nationwide population-based Danish Multiple Sclerosis Registry provided data linked with the Danish Income Statistics Register and the Danish Rational Economic Agents Model (DREAM) database. The prevalence of socioeconomic milestones of the current MS population was compared with healthy controls and the risks of reaching socioeconomic milestones were assessed using cause-specific Cox models and cumulative incidence functions compared to healthy controls. Results: The current Danish population of patients with MS of working age (18–65 years of age) consists of 11,287 patients, of which 29.3% was older than 55 years. In 2018, 38.0% of all patients and 18.9% of controls had no income from earnings, whereas 30.5% of all patients and 7.7% of controls received disability pension. The risk of losing all income from earnings was higher for patients with MS with a hazard ratio (HR) peaking at of 4.0 (95% CI, 3.8–4.2) for the ages of 45–54 years. The risk of receiving disability pension was much higher for patients with MS peaking at a HR of 22.6 (95% CI, 20.9–24.4) for the ages of 25–34 years. Likewise, the absolute risks of both outcomes were higher for the patients with MS at all ages. Conclusion: Danish patients with MS are at a higher risk of losing all income from earnings and at a much higher risk of receiving disability pension compared with healthy controls.