Prevalence and incidence of multiple sclerosis in the Netherlands.

Background: The rising prevalence estimates of multiple sclerosis (MS) globally underscore the imperative for up-to-date epidemiological data specific to the Netherlands.

Methods: Data from two Dutch healthcare databases (Nivel Primary Care Database and Vektis Database) comprising both general practices and hospital electronic health records in 2019 were combined to assess age- and sex-standardized MS prevalence and incidence estimates. Differences in prevalence estimates based on latitude and between primary versus secondary care records were examined.

Discontinuation of First-Line Disease-Modifying Therapy in Patients With Stable Multiple Sclerosis: The DOT-MS Randomized Clinical Trial.

Importance: Increasing numbers of people with multiple sclerosis (MS) use disease-modifying therapy (DMT). Long-term stable disease while taking such medications provides a rationale for considering DMT discontinuation given patient burden, costs, and potential adverse effects of immunomodulating therapy.

Objective: To investigate whether first-line DMT can be safely discontinued in patients with long-term stable MS.

Feasibility of Simon 2-Stage Futility Trials in Early Parkinson Disease: Analysis of the PRECEPT and DATATOP Trial Datasets.

Background And Objectives: Disease-modifying treatments (DMTs) are a major unmet need in Parkinson disease (PD). To date, trials investigating DMT candidates in PD most often used a randomized controlled trial (RCT) design. Unfortunately, RCTs to date have not led to a breakthrough, in part because of the large sample sizes and length of follow-up required.

Serum neurofilament light and glial fibrillary acidic protein levels are not associated with wearing-off symptoms in natalizumab-treated multiple sclerosis patients.

Background: Biomarkers of neuronal and axonal damage (serum neurofilament light (sNfL) and serum glial fibrillary acidic protein (sGFAP)) may provide insight into the aetiology of natalizumab wearing-off symptoms (WoSs).

Objectives: We investigated the longitudinal association between and predictive value of sNfL and sGFAP and the occurrence of WoS in MS patients treated with natalizumab.

Methods: We performed longitudinal measurements of sNfL and sGFAP in NEXT-MS trial participants who completed a questionnaire about WoS.

Aging is associated with reduced inflammatory disease activity independent of disease duration in relapsing multiple sclerosis trial populations.

Background: Higher age is associated with less inflammatory disease activity in relapsing-remitting multiple sclerosis (RRMS). It is unknown whether age itself or disease duration underlies this association.

Objectives: This study investigated the effects of age, disease duration, and inflammatory disease activity in people with RRMS.

Prospective trial of natalizumab personalised extended interval dosing by therapeutic drug monitoring in relapsing-remitting multiple sclerosis (NEXT-MS).

Background: Extended interval dosing (EID) of natalizumab is a promising strategy to optimise treatment in multiple sclerosis (MS). Personalised EID by therapeutic drug monitoring can enable further extension of treatment intervals.

Methods: The NEXT-MS trial is an investigator-initiated prospective phase IV non-randomised study.

Relapse recovery in relapsing-remitting multiple sclerosis: An analysis of the CombiRx dataset.

Background: Clinical relapses are the defining feature of relapsing forms of multiple sclerosis (MS), but relatively little is known about the time course of relapse recovery.

Objective: The aim of this study was to investigate the time course of and patient factors associated with the speed and success of relapse recovery in people with relapsing-remitting MS (RRMS).

Methods: Using data from CombiRx, a large RRMS trial (clinicaltrials.

Threshold definitions for significant change on the timed 25-foot walk and nine-hole peg test in primary progressive multiple sclerosis.

Background And Purpose: The timed 25-foot walk (T25FW) and nine-hole peg test (NHPT) exhibit random variability in the short term. A threshold of ≥20% change from baseline has been used to indicate true disability change, but other threshold definitions may be better suited to exclude false and include true change events. The aim of this study was to use patient-level original trial data to investigate the short-term variation in T25FW and NHPT, and to compare its extent with disability change at 12-month follow-up in people with primary progressive multiple sclerosis (PPMS).

Association of age and inflammatory disease activity in the pivotal natalizumab clinical trials in relapsing-remitting multiple sclerosis.

Background: Focal inflammatory disease activity in relapsing-remitting multiple sclerosis (RRMS) diminishes with increasing age. Here we use patient-level data from randomised controlled trials (RCTs) of natalizumab treatment in RRMS to investigate the association of age and inflammatory disease activity.

Methods: We used patient-level data from the AFFIRM (natalizumab vs placebo in relapsing-remitting MS, NCT00027300) and SENTINEL (natalizumab plus interferon beta vs interferon beta in relapsing remitting MS, NCT00030966) RCTs.

Association between age and inflammatory disease activity on magnetic resonance imaging in relapse onset multiple sclerosis during long-term follow-up.

Background And Purpose: Inflammatory disease activity in multiple sclerosis (MS) decreases with advancing age. Previous work found a decrease in contrast-enhancing lesions (CELs) with age. Here, we describe the relation of age and magnetic resonance imaging (MRI) measures of inflammatory disease activity during long-term follow-up in a large real-world cohort of people with relapse onset MS.

Longitudinal Changes in Cognitive Test Scores in Patients With Relapsing-Remitting Multiple Sclerosis: An Analysis of the DECIDE Dataset.

Background And Objectives: Cognitive impairment is a common and impactful symptom of relapsing-remitting multiple sclerosis (RRMS). Cognitive outcome measures are often used in cross-sectional studies, but their performance as longitudinal outcome measures in clinical trials is not widely researched. In this study, we used data from a large clinical trial to describe change on the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT) over up to 144 weeks of follow-up.

The nine hole peg test as an outcome measure in progressive MS trials.

Background: The nine-hole peg test (NHPT) is the outcome measure with the least change in secondary and primary progressive MS (SPMS and PPMS) trials. The Standard NHPT is defined as the average of four measurements, two in each hand. Little is known about the performance of alternative NHPT scoring methods as longitudinal outcome measures in progressive MS.

The MSIS-29 and SF-36 as outcomes in secondary progressive MS trials.

Background: Patient-reported outcome measures (PROMs) are often used in clinical research, but little is known about their performance as longitudinal outcomes.

Methods: We used data from ASCEND, a large SPMS trial ( = 889), to investigate changes on the Short Form Health Survey 36 (SF-36 v2) and the Multiple Sclerosis Impact Scale (MSIS-29) over 2 years of follow-up.

Results: PROM scores changed little over the 2 years of follow-up.

The timed 25-foot walk is a more sensitive outcome measure than the EDSS for PPMS trials: an analysis of the PROMISE clinical trial dataset.

Background: Clinical trials in primary progressive MS (PPMS) generally use the Expanded Disability Status Scale (EDSS) as their primary outcome measure, although different clinical outcomes may be more useful. Disability worsening in PPMS trials may be influenced by baseline factors, such as age, sex, and contrast-enhancing lesions.

Methods: We used the dataset of PROMISE, a large randomized controlled trial of glatiramer acetate (GA) versus placebo, to compare the clinical outcomes EDSS, timed 25-foot walk (T25FW), and nine-hole peg test (NHPT).

Impact of clinical outcomes and imaging measures on health-related quality of life in secondary progressive MS.

Background: Health-related quality of life (HRQOL) outcomes are often included as secondary outcomes in clinical trials in secondary progressive MS (SPMS), but little is known about the longitudinal association of HRQOL and clinical and imaging outcome measures in SPMS.

Objective: To assess the association of change in clinical and imaging outcomes with HRQOL in people with SPMS.

Methods: We used data from ASCEND, a large randomized controlled trial ( = 889), to investigate the association of significant worsening on the Expanded Disability Status Scale (EDSS), Timed 25 Foot Walk (T25FW), Nine Hole Peg Test (NHPT), Symbol Digit Modalities Test (SDMT), and change in lesional and volumetric imaging outcomes with significant worsening on the 36-Item Short Form Health Survey (SF-36) and the Multiple Sclerosis Impact Scale (MSIS-29) during 2 years of follow-up using logistic regression models.

Early first-line treatment response and subsequent disability worsening in relapsing-remitting multiple sclerosis.

Background And Purpose: Treatment success in relapsing-remitting multiple sclerosis (RRMS) is generally determined using relapse frequency and magnetic resonance imaging (MRI) activity in the first 6 or 12 months on treatment. The association of these definitions of short-term treatment success with disability worsening and disease activity in the longer term is unclear. In this study, we investigated risk factors associated with early first-line treatment failure in RRMS, and the association of early treatment failure with subsequent disability worsening or "no evidence of disease activity" (NEDA-3) status.

Comparison of the EDSS, Timed 25-Foot Walk, and the 9-Hole Peg Test as Clinical Trial Outcomes in Relapsing-Remitting Multiple Sclerosis.

Background And Objectives: Clinical trials in relapsing-remitting multiple sclerosis (RRMS) usually use the Expanded Disability Status Scale (EDSS) as their primary disability outcome measure, while the more recently developed outcomes timed 25-ft walk (T25FW) and 9-hole peg test (NHPT) may be more useful and patient relevant. The objective of this work was to compare the EDSS to the T25FW and NHPT in a large RRMS randomized controlled trial (RCT) dataset.

Methods: We used the dataset from Combination Therapy in Patients With Relapsing-Remitting Multiple Sclerosis (CombiRx) (clinicaltrials.

Smoking, obesity, and disability worsening in PPMS: an analysis of the INFORMS original trial dataset.

Background: Smoking and obesity are recognized modifiable risk factors associated with a higher MS incidence, but their impact on physical and cognitive disability worsening is less clear.

Objective: To investigate the impact of smoking and obesity on disability worsening in primary progressive MS (PPMS).

Methods: We used data from INFORMS (clinicaltrials.

Association of Age With Contrast-Enhancing Lesions Across the Multiple Sclerosis Disease Spectrum.

Background And Objectives: To investigate the association of age and the presence of contrast-enhancing lesions (CELs) on cranial MRI scans in different disease courses of multiple sclerosis (MS), we describe the frequency of CELs as a function of age in 4 large randomized controlled trial (RCT) datasets.

Methods: Using original trial data from CombiRx (Combination Therapy in Patients With Relapsing-Remitting Multiple Sclerosis; clinicaltrials.gov identifier NCT00211887), a trial in relapsing-remitting MS; ASCEND (A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Participants With Secondary Progressive Multiple Sclerosis; clinicaltrials.

MRI brain volume loss, lesion burden, and clinical outcome in secondary progressive multiple sclerosis.

Background: Magnetic resonance imaging (MRI) of brain volume measures are widely used outcomes in secondary progressive multiple sclerosis (SPMS), but it is unclear whether they are associated with physical and cognitive disability.

Objective: To investigate the association between MRI outcomes and physical and cognitive disability worsening in people with SPMS.

Methods: We used data from ASCEND, a large randomized controlled trial ( = 889).

A comparison of clinical outcomes in PPMS in the INFORMS original trial data set.

Background: The expanded disability status scale (EDSS) is the standard clinical outcome measure in primary progressive multiple sclerosis (PPMS), even though the timed 25-foot walk (T25FW), nine-hole peg test (NHPT) or combinations of these measures may be more useful. The paced auditory serial addition test (PASAT) is a widely used cognitive measure in MS, but little is known about change in PASAT scores over time in PPMS.

Objective: The objective of this study is to compare clinical outcome measures in a large PPMS trial data set.

Is the Symbol Digit Modalities Test a useful outcome in secondary progressive multiple sclerosis?

Background: It is unclear which cognitive outcome measure is the most useful for clinical trials in multiple sclerosis. To investigate the usefulness of the Symbol Digit Modalities Test (SDMT) as a clinical outcome measure in secondary progressive multiple sclerosis (SPMS), we describe the frequency of worsening and improvement events in a large randomized controlled trial (RCT) dataset.

Methods: Using original trial data from the ASCEND trial (n = 889), a recent large RCT in SPMS, we describe worsening and similarly defined improvement with and without 3-month confirmation on the SDMT in the whole trial cohort and unconfirmed worsening and improvement on the Paced Auditory Serial Addition Test (PASAT) in a smaller subset (n = 107).

Reliability of Outcome Measures in Clinical Trials in Secondary Progressive Multiple Sclerosis.

Objective: To investigate the reliability of clinical outcomes in secondary progressive multiple sclerosis (SPMS) trials, we compared the frequency of progression and improvement events on different clinical outcome measures in the placebo arms of 2 large randomized controlled trial (RCT) datasets.

Methods: Using original trial data from the placebo arms of IMPACT (International MS Secondary Progressive Avonex Controlled Trial) and ASCEND (A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Participants With Secondary Progressive Multiple Sclerosis), 2 large RCTs in SPMS, we compared disability progression and similarly defined improvement with and without 3- or 6-month confirmation on the outcome measures Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), and their combinations.

Results: In both datasets, the EDSS showed the highest rates of improvement over time, and the smallest difference between progression and improvement rates, followed by the T25FW and the 9HPT.