Disease-modifying treatment and disability progression in subclasses of patients with primary progressive MS: results from the Big MS Data Network.

Background: Effectiveness of disease-modifying treatment (DMT) in people affected by primary progressive multiple sclerosis (PPMS) is limited. Whether specific subgroups may benefit more from DMT in a real-world setting remains unclear. Our aim was to investigate the potential effect of DMT on disability worsening among patients with PPMS stratified by different disability trajectories.

Torben Fog - A Danish pioneer in a multi-faceted spectrum of multiple sclerosis research.

Torben Fog was committed to multiple sclerosis (MS) research for more than four decades, starting before the defence of his thesis in 1948 and lasting until his death in 1987. His research was multi-facetted, making him one of the great pioneers in the study of essential parts of the pathology, immunology and treatment of MS. He has contributed with meticulous studies of the MS plaques, documenting the perivenous distribution of plaques in the spinal cord.

Using instrumental variables to correct for bias in real-world cohort studies of the effects of disease-modifying treatment in MS.

Background: Estimating the effect of disease-modifying treatment of MS in observational studies is impaired by bias from unmeasured confounders, in particular indication bias.

Objective: To show how instrumental variables (IVs) reduce bias.

Methods: All patients with relapsing onset of MS 1996-2010, identified by the nationwide Danish Multiple Sclerosis Registry, were followed from onset.

Heterogeneity on long-term disability trajectories in patients with secondary progressive MS: a latent class analysis from Big MS Data network.

Background: Over the decades, several natural history studies on patients with primary (PPMS) or secondary progressive multiple sclerosis (SPMS) were reported from international registries. In PPMS, a consistent heterogeneity on long-term disability trajectories was demonstrated. The aim of this study was to identify subgroups of patients with SPMS with similar longitudinal trajectories of disability over time.

Changes in prognosis of the Danish multiple sclerosis population over time.

Background: The course of multiple sclerosis (MS) appears to be milder in recent decades.

Objective: To investigate how time from onset to disability milestones and how demographic and clinical characteristics have changed through subsequent onset cohorts of patients with MS.

Methods: In the nationwide Danish Multiple Sclerosis Registry, we have registered all 13,562 Danish patients with onset of MS or clinically isolated syndrome from 1996 through 2020.

Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis.

Background: Natalizumab and fingolimod are used as high-efficacy treatments in relapsing-remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies.

Quantitative effect of sex on disease activity and disability accumulation in multiple sclerosis.

Objective: To quantify sex differences in activity and severity of multiple sclerosis (MS) and how it depends on disease duration and time since clinical onset.

Methods: All Danish citizens with onset of relapsing MS since 1996 who have received disease-modifying therapy have been followed with annual or biannual control visits with mandatory notification of the Danish Multiple Sclerosis Registry. Men and women were compared by the inverse probability of being female.

Apparent changes in the epidemiology and severity of multiple sclerosis.

Multiple sclerosis (MS) is an immunological disease that causes acute inflammatory lesions and chronic inflammation in the CNS, leading to tissue damage and disability. As awareness of MS has increased and options for therapy have come into use, a large amount of epidemiological data have been collected, enabling studies of changes in incidence and disease course over time. Overall, these data seem to indicate that the incidence of MS has increased, but the course of the disease has become milder, particularly in the 25 years since the first disease-modifying therapies (DMTs) became available.

Relapses add to permanent disability in relapsing multiple sclerosis patients.

Objective: Whether relapses have direct effects on permanent disability in multiple sclerosis is still an unsettled issue. We aimed at investigating the cumulative effect of breakthrough relapses on the Expanded Disability Status Scale (EDSS) in relapsing-onset MS patients under disease modifying therapy (DMT).

Methods: From the Danish Multiple Sclerosis Registry we identified all patients in Denmark with relapsing-onset MS who had started DMT and followed them from the first day of treatment.

The effectiveness of natalizumab vs fingolimod-A comparison of international registry studies.

Background: Natalizumab and fingolimod were the first preparations recommended for disease breakthrough in priorly treated relapsing-remitting multiple sclerosis. Of three published head-to-head studies two showed that natalizumab is the more effective to prevent relapses and EDSS worsening.

Methods: By re-analyzing original published results from MSBase, France, and Denmark using uniform methodologies, we aimed at identifying the effects of differences in methodology, in the MS-populations, and at re-evaluating the differences in effectiveness between the two drugs.

Early treatment delays long-term disability accrual in RRMS: Results from the BMSD network.

Background: The optimal timing of treatment starts for achieving the best control on the long-term disability accumulation in multiple sclerosis (MS) is still to be defined.

Objective: The aim of this study was to estimate the optimal time to start disease-modifying therapies (DMTs) to prevent the long-term disability accumulation in MS, using a pooled dataset from the Big Multiple Sclerosis Data (BMSD) network.

Methods: Multivariable Cox regression models adjusted for the time to first treatment start from disease onset (in quintiles) were used.

Seasonal patterns of relapse and disability in Danish MS patients: A population-based cohort study.

Background: The importance of environmental risk factors in the onset of multiple sclerosis (MS) has been studied extensively. Similarly, a growing number of studies address the importance of environmental factors, including seasonality, for ongoing activity of established disease. Specifically, past research demonstrates higher rates of relapse activity in summer months among individuals with MS.

The Danish Multiple Sclerosis Registry.

Objectives: The Danish Multiple Sclerosis Registry is the oldest operative and nationwide MS registry. We present The Danish Multiple Sclerosis Registry with its history, data collection, scientific contribution, and national and international research collaboration.

Materials And Methods: Detailed description of data collection, completeness, quality optimizing procedures, funding, and legal, ethical and data protection issues are provided.

A population-based epidemiological study of neuromyelitis optica spectrum disorder in Hungary.

Background And Purpose: The goal of this study was to determine the prevalence and incidence of neuromyelitis optica spectrum disorder (NMOSD) in Hungary based on the 2015 International Panel of NMO Diagnosis (IPND) criteria.

Methods: A retrospective population-based cohort study was conducted of 6.4 million Hungarians (age ≥ 16 years) between 1 January 2006 and 31 December 2016.

Multiple sclerosis among first- and second-generation immigrants in Denmark: a population-based cohort study.

Multiple sclerosis is a disease with a highly variable incidence worldwide. While knowledge about multiple sclerosis risk factors has grown over the years, the aetiology of multiple sclerosis has still not been fully established. We examined multiple sclerosis incidence rates among first-generation immigrants in Denmark, a high-incidence country, and their Danish-born children (second-generation immigrants), to evaluate the importance and timing of exposure to environmental factors in the aetiology of multiple sclerosis.

Worsening of disability caused by relapses in multiple sclerosis: A different approach.

Background: In multiple sclerosis (MS) the quantitative role of relapses in Expanded Disability Status Scale (EDSS) worsening beyond the recovery phase is not well known. Most studies have examined the predictive role of early relapses in more distant endpoints. Relapses and worsening may be associated because they could be independent effects of the same underlying disease characteristics without causal relationship.