Background and purpose
To assess long‐term treatment effectiveness of disease‐modifying therapy (DMT) initiated early in disease course versus later treatment start.
Methods
We included all Danish ...patients with multiple sclerosis (MS) treated with DMT through two nationwide population‐based MS registries. Patients were categorized as early treated if treatment started within 2 years after the first MS symptom (n = 2316) and later treated if treatment started between 2 and 8 years after clinical onset (n = 1479). We compared time from treatment start to progression to an Expanded Disability Status Scale (EDSS) score of 6 and mortality between cohorts as hazard ratio (HR) using a Cox proportional hazards model with adjustment for stabilized inverse probability of treatment weights. Several sensitivity analyses were conducted.
Results
The median follow‐up time of 3795 patients was 7.0 (range 0.6–19.5) years for the EDSS score of 6 outcome and 10.4 (range 1.2–20.1) years for the mortality outcome. Patients with later treatment start showed a 42% increased hazard rate of reaching an EDSS score of 6 compared with the early‐treated patients HR, 1.42; 95% confidence interval (CI), 1.18–1.70; P < 0.001. When stratified by sex, the increased hazard among later‐treated women persisted (HR, 1.53; 95% CI, 1.22–1.93; P < 0.001), whereas the HR was lower in men (1.25; 95% CI, 0.93–1.69; P = 0.15). Mortality was increased by 38% in later starters (HR, 1.38; 95% CI, 0.96–1.99; P = 0.08).
Conclusions
Patients who started treatment with DMT later reached an EDSS score of 6 more quickly compared with patients who started early and the delay showed a tendency to shorten time to death. Our results support the use of early treatment.
Registers of multiple sclerosis in Denmark Koch-Henriksen, N.; Magyari, M.; Laursen, B.
Acta neurologica Scandinavica,
July 2015, Letnik:
132, Številka:
S199
Journal Article
Recenzirano
Odprti dostop
There are two nationwide population‐based registers for multiple sclerosis (MS) in Denmark. The oldest register is The Danish Multiple Sclerosis Registry (DMSR), which is an epidemiological register ...for estimation of prevalence and incidence of MS and survival, and for identifying exposures earlier in life that may affect the risk of MS. This register has no systematic follow‐up data except for survival. The DMSR has over the years published nationwide incidence‐ and prevalence data from Denmark and has been involved in a number of ‘historical prospective’ studies to elucidate the association between a number of different environmental exposures in the past and the subsequent risk of MS. Some of these studies have been able to exonerate suspected risk factors. The other register, the nationwide Danish Multiple Sclerosis Treatment Register, is a follow‐up register for all patients who have received disease‐modifying treatments since 1996. It has, in particular, contributed to the knowledge of the role of antibodies against the biological drugs used for the treatment of MS.
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. Possible NMOSD patients were selected via multistage re‐evaluation from multiple sources. Crude and sex‐ and serostatus‐specific prevalence (per 100 000 persons) and incidence rates (per 1 000 000 person‐years) from 2006 to 2015 were estimated and age‐adjusted rates were determined.
Results
Of 2262 study candidates, 154 NMOSD patients (age ≥ 16 years) with onset until 31 December 2016 were identified based on 2015 IPND criteria. The prevalence analysis on 1 January 2016 included 123 NMOSD living cases, resulting in a prevalence of 1.91 95% confidence interval (CI) 1.52–2.28 per 100 000 persons. The 101 incident cases emerging from the observed 76 394 288 person‐years provided an incidence rate of 1.32 (95% CI 1.08–1.61) per 1 000 000 person‐years. Age‐adjusted prevalence was 1.87 (95% CI 1.56–2.23) per 100 000 persons and incidence was 1.20 (95% CI 0.98–1.46) per 1 000 000 person‐years.
Conclusions
In this first report of a large population‐based epidemiological study from an Eastern European Caucasian population using robust case validation, a greater prevalence and incidence of NMOSD was found compared to previous large studies in Caucasian populations.
Background and purpose
The social and economic consequences of comorbidity in multiple sclerosis (MS) are largely unexplored. Differences were investigated in income and in the rate of broken ...relationships between cases of MS with and without chronic comorbidity.
Methods
We conducted a nationwide cohort study including all incident cases of MS in Denmark with clinical MS onset between 1980 and 2005. The difference in income was investigated at MS onset and 5 and 10 years after MS onset. The difference in the rate of broken relationships was investigated in subjects who were in a relationship at MS onset or who entered a relationship after MS onset. We used logistic, multiple linear and Poisson regression analyses.
Results
Cases of MS with somatic comorbidity had increased odds of low incomes both 5 years {odds ratio (OR), 1.41 95% confidence interval (CI), 1.19–1.67; P < 0.0005} and 10 years OR, 1.37 (95% CI, 1.17–1.60); P < 0.0005 after MS onset. The odds of a low income with psychiatric comorbidity was increased 10 years after MS onset OR, 3.06 (95% CI, 1.47–6.37); P = 0.003. The rate of broken relationships was increased in cases of MS with any somatic comorbidity incidence rate ratio, 1.46 (95% CI, 1.32–1.61); P < 0.0005.
Conclusions
Our results underscore the burden of comorbidity in MS on patients, their partners and society.
Background
Initiation of fingolimod treatment is associated with a transient decrease of heart rate, and atrioventricular (AV) conduction block may occur.
Objective
To evaluate the therapeutic effect ...and safety of fingolimod treatment in MS patients in Denmark with focus on cardiac and pulmonary side effects at treatment onset.
Materials & methods
We analysed data from the first 496 fingolimod‐treated Danish patients, observed for at least 3 months. In a subset of 204 patients, we monitored cardiac and pulmonary adverse effects following treatment initiation.
Results
The overall annualized relapse rate (ARR) was 0.37 (95% CI 0.31–0.44); 0.22 (95% CI 0.03–0.81) in de novo‐treated patients, 0.29 (95% CI; 0.23–0.37) in patients switching from IFN‐beta or GA and 0.46 (9 5% CI 0.34–0.60) after natalizumab. In the subset of 204 patients, 8 (3.9%) required prolonged cardiac monitoring due to bradycardia and/or second‐degree AV block type I. All patients recovered spontaneously. Two patients discontinued fingolimod. Eleven (5.4%) patients reported respiratory complaints and two of these patients discontinued treatment.
Conclusions
Fingolimod appears to be safe and effective in MS patients in a clinical setting. Mild cardiac adverse effects occurred at a similar rate as in clinical trials.
Background and purpose
Case reports have observed a co‐occurrence of multiple sclerosis (MS) and Parkinson's disease (PD) and it has been hypothesized that MS lesions could affect dopaminergic ...pathways causing parkinsonism. Our aim was to examine the association between MS and PD in a historically prospective cohort study using Danish nationwide register data.
Methods
Multiple sclerosis patients identified in the Multiple Sclerosis Registry were followed for PD from 1977 to 2011 in the National Patient Register. As measures of relative risk, ratios of observed to expected incidence rates of first hospitalization for PD amongst persons with MS were used, i.e. standardized incidence ratios (SIRs) with 95% confidence intervals (CIs).
Results
Amongst 15 557 MS patients 26 cases of PD were observed versus 26.51 expected, reflecting no overall increased risk of PD (SIR 0.98, 95% CI 0.67–1.44). Similar estimates were seen for female (SIR 0.99, 95% CI 0.58–1.67) and male MS patients (SIR 0.97, 95% CI 0.55–1.72). Likewise, no increased risk of PD amongst MS patients was observed in a robustness analysis backdating the date of diagnosis of PD by 5 years to account for the time lag between disease onset and first hospital contact with PD (SIR 0.57, 95% CI 0.32–1.00).
Conclusion
Our data do not suggest an increased risk of PD amongst patients with MS.
Introduction
The claim of detection of several environmental risk factors for multiple sclerosis (MS), some of them new, makes the research of population‐based MS registers for critical review or ...confirmation of alleged associations more relevant than ever before.
Aims
To present examples of the use and important contributions from the Danish MS Registry (DMSR) over decades.
Methods
The DMSR has through more than six decades registered virtually all patients with MS in Denmark, using multiple sources of notification and has been used for descriptive epidemiology, follow‐up studies, studies of comorbidity and ‘historical prospective’ studies of proposed risk factors for MS.
Results
Based on research from DMSR, we have found that female incidence of multiple sclerosis in Denmark has increased considerably; that patients with MS loose their working ability and their spouses/partners at a much higher rate than the background population; that patients with MS have a considerable excess mortality which seem to have decreased over several centuries decades ‐ not centuries, also before the era of disease modifying treatment; that fewer patients with MS than expected from the population get diagnosed with or die from cancer; that infectious mononucleosis increases the risk of MS; that head trauma and a number of occupational exposures, for example, nurses, utility workers, exposure to solvents do not carry an enhanced risk of MS.
Conclusion
The DMSR has, as an example of long‐lasting population‐based registers, proven to be an effective tool for studying MS epidemiology. In future, the need for this kind of registers will continue, as biology or immunology cannot stand alone.
Background
Gender appears to play a role in incidence and disease course of multiple sclerosis (MS).
Objective
The objective was to determine whether male and female patients with MS respond ...differently to interferon‐beta treatment in terms of reduction in relapse rates.
Methods
We included all 2033 patients with relapsing–remitting MS who started treatment with interferon‐beta from 1996 to 2003, identified from the Danish Multiple Sclerosis Treatment Register. We defined neutralizing antibody (NAb)‐positive and NAb‐negative periods in the single patient by the results of the NAb tests. Patients served as their own controls, and relapse rates were compared between NAb‐negative and NAb‐positive periods.
Results
NAbs significantly abrogated the interferon‐beta treatment efficacy in both genders. The all‐over women:men relapse rate ratio irrespective of NAb status was 1.47 (95%CI; 1.28–1.68). In a generalized linear Poisson models analysis with relapse counts as response variable, the main effects NAbs, sex, age at treatment start and number of relapses in 2 years before treatment start were strongly significant, but the effect of NAbs on relapse rates did not differ significantly between men and women.
Conclusion
As NAbs influenced the on‐treatment relapse rates strongly in both sexes but without statistical significant difference, there is no indication of different effects of interferon‐beta in men or women.
Introduction: Previous studies of natalizumab (Tysabri®) in relapsing multiple sclerosis (MS) patients have included patients with moderate disease activity. We studied a patient population with ...high disease activity.
Patients and Methods: We analyzed data from 234 consecutive, natalizumab‐treated patients, followed for at least 3 months. Three groups of patients were eligible for natalizumab therapy: patients with two or more documented relapses or sustained increase of 2 EDSS points on disease modifying therapy (DMT) in the previous year; patients switching from mitoxantrone; and patients with very active MS as de novo therapy.
Results: During a median observation time of 11.3 months (range 3.0–21.5) the annualized relapse rate decreased to 0.68 from a pre‐treatment rate of 2.53 (73% reduction). We assessed the annualized relapse rate in three subgroups: (i) 0.83 in 14 (6.0%) de novo treated patients; (ii) 0.71 in 175 (74.8%) patients with ≥2 relapses or sustained increase in EDSS of ≥2 points on a first‐line DMT; and (iii) 0.56 in 45 (19.2%) patients switching from mitoxantrone. Nine anaphylactoid reactions, two severe, were reported. Out of 215 patients 7 (3%) were persistently positive for antibodies to natalizumab.
Conclusions: Tysabri appears to be effective in MS patients with high disease activity, but the relapse rate was higher than in the pivotal study after the first treatment year. This is likely to reflect differences in disease activity before the initiation of natalizumab treatment.
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