Clinical trial NCT05446285: Multiple Sclerosis Outcome Determination Evaluating Real Differences After TimE
Official title: Multiple Sclerosis Outcome Determination Evaluating Real Differences After TimE
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Relapsing Remitting Multiple Sclerosis
Lead sponsor: NHS Greater Glasgow and Clyde
Sponsor class: OTHER
Collaborators: name: Biogen
First posted: 2022-07-06
Enrollment: 245
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: As above, Patients diagnosed with Relapsing-Remitting Multiple Sclerosis (RRMS) in 2010-11 in Scotland, as held on the Scottish Multiple Sclerosis Register

Brief summary: To provide real world evidence evaluating whether a strategy of early initiation and escalation of disease modifying treatment (DMT) in relapsing-remitting multiple sclerosis (RRMS) affects disease outcome over a 10 year period. Our aim is to provide evidence for clinicians and patients regarding the benefits and risks of early initiation and active escalation of disease modifying treatments (DMTs) in relapsing-remitting multiple sclerosis (RRMS), using real world data.

Detailed description: We will compare efficacy and safety outcomes for patients with RRMS managed with a) an early initiation and escalation policy and b) an expectant and delayed treatment policy, using patients from the National Health Service Greater Glasgow and Grampian MS centres. Initiation and escalation of DMTs will be the interventions under study and a detailed contemporary clinico-radiological assessment will be undertaken to compare outcomes in the differently treated cohorts over the first 10 years following diagnosis.

To capture and analyse both prospective and retrospective data we will use the OPTIMISE portal. This is a database tool under development in Imperial College London which aims to provide a secure IT framework to capture patient-centred data in MS research. Its aim is to facilitate the capture of prospective longitudinal, standardised clinical and patient-centred data, ideally with an ease that would allow it to be used as an adjunct to routine clinical practice. It will ultimately provide open-source software for management of MS data, integrating anonymised information from multiple centres. Our proposed registry study will utilise the OPTIMISE portal and platform for data capture and analysis - this will serve to pilot the platform before its implementation on a wider scale in a variety of different projects, including the nationwide Scottish DMT database currently under development.

In order to compare these non-randomised patient groups we will use propensity score matching (PSM). This statistical method can account for all the known variables that inform the decision-making process of DMT initiation and escalation, and is used in observational studies to mimic the process of randomisation. The decision to initiate or escalate DMTs in RRMS in clinical practice is based on both patient and disease related factors. Patients with more clinically severe disease are more likely to have DMTs initiated or escalated. For DMT initiation, we will calculate the propensity score based on known prognostic factors at the time of diagnosis that predict a more severe disease course, which would suggest the need for DMT initiation. For DMT escalation, we will evaluate the disease course of each patient over the first 3 years of follow up, using recent guidance on clinical and radiological features that suggest escalation to treatment or more effective treatment is required. These factors will be included as weighted variables to generate a summary number (0-1), the Propensity Score (PS): a higher propensity score would suggest a higher likelihood of being in the treated or escalated group.

Once each patient has been assigned a propensity score, we will assess the actual use of DMTs, matching treated and non-treated, and escalated and non-escalated patients into pairs for comparison of outcome. We anticipate that more patients with a high propensity score (and therefore a higher propensity to treatment) will have been initiated or escalated onto DMTs in Greater Glasgow in comparison to Grampian. Prognostically similar patients managed differently within a centre will also be matched, since the purpose is to compare patients and not centres. If data from the Glasgow and Grampian Centres do not provide enough propensity-matched pairs, data from the Edinburgh and Dundee centres can also be extracted.

Phase 1 - completed This retrospective phase has been completed and examined whether patients with RRMS are treated differently within Scotland despite similar disease severity. We established the proportion of patients from each centre with a high propensity score for DMT initiation or escalation who were 'treated' and 'escalated', or not, respectively. This allowed us to identify pairs for comparison of outcomes in the prospective phase of the study (Phases 2).

Phase 2 - proposed Propensity score-matched patients who were managed differently during phase 1 will be invited for a clinical assessment and MRI in the prospective phase of the study. This will be 10 years on from date of diagnosis. Contemporary clinical assessment will include physical and cognitive evaluations as detailed below. Updated radiological assessment with MRI will assess T2 and T1 lesions and total brain volume. Patients will also be asked to provide a variety of patient reported outcome measures (PROMs) by completing validated questionnaires to describe their perceived disease status. After assessments are complete, a clinical history via a structured questionnaire will be performed to capture disease activity and changing/escalation of treatment from diagnosis to point of assessment 10 years later.

Eligibility criteria: Inclusion Criteria:

* Patients diagnosed with Relapsing-Remitting Multiple Sclerosis (RRMS) in 2010-11 in Scotland, as held on the Scottish Multiple Sclerosis Register

Exclusion Criteria:

* none

Primary outcomes:
measure: Mean Expanded Disability Status Scale (EDSS) score at prospective assessment.
timeFrame: Single visit assessment competed by Dec 2022
Secondary outcomes:
measure: Proportion experiencing (serious) adverse events in first 9-10 years after diagnosis
timeFrame: Single visit assessment competed by Dec 2022
measure: Proportion attaining Expanded Disability Status Scale (EDSS) 3.0, 4.0 and 6.0
timeFrame: Single visit assessment competed by Dec 2022
measure: Mean change in Expanded Disability Status Scale (EDSS) between treatment groups
timeFrame: Single visit assessment competed by Dec 2022
measure: Mean scores on patient reported outcome measure Multiple Sclerosis Impact Scale -29 (MSIS-29) at prospective assessment
timeFrame: Single visit assessment competed by Dec 2022
measure: Mean Brief International Cognitive Assessment for MS (BICAMS) score at prospective assessment
timeFrame: Single visit assessment competed by Dec 2022
measure: Mean 9-Hole Peg Test (9-HPT) at prospective assessment
timeFrame: Single visit assessment competed by Dec 2022
Other outcomes:
measure: Mean scores on patient reported outcome measures (PROMs)
timeFrame: Single visit assessment competed by Dec 2022
measure: Mean volume of grey matter and whole brain volume on prospective MRI scans
timeFrame: Single visit assessment competed by Dec 2022
measure: Mean lesion volume of T2/FLAIR on prospective MRI scans
timeFrame: Single visit assessment competed by Dec 2022
Locations:
city: Glasgow
country: United Kingdom
facility: Clinical Research Facility
Study officials:
References: