An observational study in Multiple Sclerosis, Multiple Sclerosis (MS) - Relapsing-remitting and Multiple Sclerosis (MS) Primary Progressive, sponsored by Imperial College London. Recruiting at 3 sites in United Kingdom. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-27.
Sponsored by Imperial College London · Observational
Multiple sclerosis (MS) is a condition in which the immune system damages the brain and spinal cord. Treatments called disease-modifying therapies can reduce inflammation and disease activity. For some people with highly active MS, autologous haematopoietic stem cell transplantation (AHSCT) may be used. AHSCT uses a person's own blood-forming stem cells after treatment that suppresses the immune system.
REAL-MS is an observational study that will collect and analyse information from routine clinical care to compare the longer-term effectiveness and safety of AHSCT with high-efficacy disease-modifying therapies for adults with MS. High-efficacy therapies include medicines such as alemtuzumab, cladribine, natalizumab, and anti-CD20 antibody treatments, as well as other high-efficacy disease-modifying therapies that may become available during the study.
REAL-MS is a multicentre, observational, longitudinal, database-based cohort study designed to evaluate the comparative effectiveness and safety of AHSCT and high-efficacy disease-modifying therapies (H-DMTs) in adults with multiple sclerosis (MS) treated in routine clinical practice. The principal comparison is AHSCT versus H-DMTs; clinically relevant comparisons between individual H-DMTs may also be undertaken where data quality, follow-up duration, and sample size are sufficient.
The study addresses the need for longer-term comparative evidence from real-world clinical settings. Treatment allocation is not determined by the protocol. Decisions about treatment initiation, discontinuation, switching, and other aspects of clinical management remain the responsibility of the treating clinical team and patient as part of usual care. No additional treatment, investigations, or clinical visits are required solely for research purposes.
The registry includes retrospective and prospective components. The retrospective component includes eligible patients treated between 1 January 2008 and 31 January 2025 whose information is available in authorised local clinical audit datasets or previously approved research datasets. Relevant data are extracted locally by authorised staff and transferred in anonymised form to the central study database. The prospective component is planned to begin in October 2026 and will collect longitudinal information from eligible participants during routine clinical follow-up. Prospective participants will provide written informed consent before study-specific data collection where required by applicable local regulations and ethics approvals. Data for the prospective component are pseudonymised before central entry; the key linking the study identifier to an individual's identity is retained securely at the local participating site and is not transferred to the coordinating centre.
Data are collected from routine clinical records using a standardised electronic case report form implemented in REDCap and hosted by Imperial College London. Data may include demographic and clinical characteristics, MS phenotype, treatment history, relapse history, disability assessments, MRI findings, routine laboratory results where available, treatment discontinuation or switching, and safety-related clinical events. Definitions for collected variables and outcomes are specified in the study case report form and associated data dictionary. The data dictionary provides variable-level definitions, coding formats, and permitted values to support consistent data collection across centres.
The registry incorporates quality-assurance measures to promote accuracy, completeness, and consistency of data. REDCap provides role-based access controls, audit trails, and data-validation functionality. Standardised data definitions and built-in validation rules are used where feasible to identify missing, inconsistent, or implausible entries. Data quality will also be supported through central review of data completeness and consistency, with queries issued to participating sites when clarification or correction is needed. Participating site investigators are responsible for local study conduct, compliance with governance requirements, and the accuracy and completeness of data submitted to the registry. The coordinating centre oversees site communication, study administration, data-collection procedures, and central data-quality processes. The study may be subject to audit by Imperial College London or relevant regulatory bodies.
As this is an observational registry, it does not undertake systematic adverse-event reporting as would be required in an interventional trial. However, safety outcomes of interest-including serious adverse events, infections or viral reactivations, hospitalisations, malignancies, secondary autoimmune diseases, treatment discontinuation due to adverse events, and mortality-will be identified from routine clinical data where available.
Analyses will follow a prespecified statistical analysis plan. Descriptive analyses will summarise baseline demographic, clinical, radiological, and treatment-related characteristics overall and by treatment group. Comparative analyses will account for the non-randomised nature of treatment allocation and the potential for baseline imbalance and confounding. Depending on the comparison and outcome, methods may include multivariable regression adjustment, propensity score matching, inverse probability of treatment weighting, propensity score stratification, and sensitivity analyses using alternative adjustment approaches. Time-to-event outcomes will generally be analysed using Kaplan-Meier methods and Cox proportional-hazards models; other outcomes will use appropriate regression methods.
Prespecified subgroup analyses may examine whether comparative outcomes differ according to factors such as MS phenotype, age, sex, baseline disability, disease duration, prior treatment exposure, baseline MRI activity, and treatment era. The extent and pattern of missing data will be described. Missing data will be addressed according to their amount, nature, and likely mechanism, using approaches such as complete-case analysis, multiple imputation, and sensitivity analyses as appropriate. Additional sensitivity analyses may assess the effect of missing MRI or disability data on outcome ascertainment.
As a multicentre registry study, the final sample size will depend on the number of eligible participants identified and enrolled across participating centres during the study period. Analyses of individual H-DMT comparisons will be performed only where there is sufficient sample size, follow-up duration, and data completeness to support reliable interpretation.
Study data will be stored securely with appropriate technical and organisational safeguards. Access is restricted to authorised personnel. Results will be reported in aggregate or otherwise non-identifiable form and may be disseminated through scientific publications, conference presentations, and, where feasible, summaries for participants, patients, and the wider public.
3,264 studies on the registry are indexed under Multiple Sclerosis; 659 are open to participants now.
This study's planned enrollment of 2,000 is above the median of 100 across 970 observational studies indexed under Multiple Sclerosis.
Browse Multiple Sclerosis studies →Imperial College London is the lead sponsor of 843 studies on the registry; 180 are open to participants now.
Of its 9 completed or terminated interventional studies of FDA-regulated products, 6 (67%) have results posted.
Counted across the registry records on this site, refreshed daily.
The study population will be drawn from adults with MS receiving routine care at participating specialist neurology and MS centres within the United Kingdom National Health Service.
Participating centres include:
Participants will be identified through local clinical services and authorised clinical audit or research datasets. The source population includes people treated with AHSCT or eligible HE-DMTs as part of standard clinical care.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adults with multiple sclerosis treated with autologous haematopoietic stem cell transplantation as part of routine clinical care.
Procedure: Autologous haematopoietic stem cell transplantation (AHSCT)
Adults with multiple sclerosis treated with an eligible high-efficacy disease-modifying therapy as part of routine clinical care, including alemtuzumab, cladribine, natalizumab, anti-CD20 antibody therapies, and other eligible therapies introduced during the study period.
Drug: High-efficacy disease-modifying therapy (HE-DMT)
Exposure to autologous haematopoietic stem cell transplantation received as part of routine clinical care for multiple sclerosis. AHSCT uses the participant's own blood-forming stem cells following immune-suppressing treatment. Treatment is not assigned or administered by the study.
Exposure to an eligible high-efficacy disease-modifying therapy received as part of routine clinical care for multiple sclerosis. Therapies may include alemtuzumab, cladribine, natalizumab, anti-CD20 monoclonal antibody therapies, and other eligible high-efficacy disease-modifying therapies available during the study. Treatment is not assigned or administered by the study.
No Evidence of Disease Activity (NEDA-3)
Composite time-to-event outcome. NEDA-3 failure is the first occurrence of a clinical relapse, MRI activity, or 6-month confirmed disability progression. Clinical relapse is new or worsening MS-related neurological symptoms lasting at least 24 hours, without fever, infection, or another explanation. MRI activity is new or enlarging T2 lesions and/or gadolinium-enhancing T1 lesions. Confirmed disability progression is assessed using the Expanded Disability Status Scale and confirmed after 6 months.
Time frame: From treatment baseline through study completion, up to 24 years
Absence of clinical relapses
Proportion of participants with no clinical relapse during follow-up. A clinical relapse is new or worsening neurological symptoms attributable to MS, lasting at least 24 hours, occurring without fever, infection, or another alternative explanation, and separated from a previous relapse by at least 30 days.
Time frame: From treatment baseline through study completion, up to 24 years
Annualised relapse rate
Number of clinical relapses per participant-year of follow-up.
Time frame: From treatment baseline through study completion, up to 24 years
Absence of MRI activity
Proportion of participants with no MRI activity during follow-up. MRI activity is defined as new or enlarging T2 lesions and/or gadolinium-enhancing T1 lesions on follow-up MRI compared with the reference scan.
Time frame: From treatment baseline through study completion, up to 24 years
Absence of 6-month confirmed disability progression (CDP)
Proportion of participants without 6-month CDP, assessed using the Expanded Disability Status Scale (EDSS). Confirmed disability progression is an increase in EDSS of 1.0 point when baseline EDSS is below 6.0, or 0.5 point when baseline EDSS is 6.0 or higher, confirmed 6 months after the reported change.
Time frame: From treatment baseline through study completion, up to 24 years
Absence of progression independent of relapse activity (PIRA)
Proportion of participants without PIRA. PIRA is defined as confirmed disability progression occurring without a relapse during the 90 days before and 30 days after the event, including the 90 days before and 30 days after confirmation.
Time frame: From treatment baseline through study completion, up to 24 years
Probability of 6-month confirmed disability improvement (CDI)
Proportion of participants with 6-month CDI, defined as a decrease in EDSS of 1.0 point when baseline EDSS is below 6.0, or 0.5 point when baseline EDSS is 6.0 or higher, confirmed 6 months after the reported change.
Time frame: From treatment baseline through study completion, up to 24 years
Time to first clinical relapse
Time from treatment baseline to the first clinical relapse.
Time frame: From treatment baseline through study completion, up to 24 years
Time to first MRI activity
Time from treatment baseline to the first MRI showing new or enlarging T2 lesions and/or gadolinium-enhancing T1 lesions compared with the reference scan.
Time frame: From treatment baseline through study completion, up to 24 years
Time to 6-month confirmed disability progression
Time from treatment baseline to the first occurrence of 6-month confirmed disability progression, assessed using EDSS criteria.
Time frame: From treatment baseline through study completion, up to 24 years
Time to progression independent of relapse activity
Time from treatment baseline to the first occurrence of PIRA, defined as confirmed disability progression not temporally associated with a clinical relapse.
Time frame: From treatment baseline through study completion, up to 24 years
Time to treatment discontinuation or switch
Time from treatment baseline to discontinuation of the initial treatment or switch to another MS disease-modifying therapy.
Time frame: From treatment baseline through study completion, up to 24 years
Serious adverse events
Number and proportion of participants with serious adverse events recorded in routine clinical data. A serious adverse event is an event that results in death, is life-threatening, requires or prolongs hospitalisation, results in significant disability or incapacity, is a congenital anomaly or birth defect, or is otherwise considered medically important.
Time frame: From treatment baseline through study completion, up to 24 years
Mortality
Number and proportion of participants who die during follow-up; cause of death and whether the death was considered treatment-related will be recorded where available.
Time frame: From treatment baseline through study completion, up to 24 years
Infections and viral reactivations
Number and proportion of participants with clinically recorded infections or viral reactivations, including JC virus seroconversion in natalizumab-treated participants and Epstein-Barr virus or cytomegalovirus reactivation after AHSCT, where available in routine clinical data.
Time frame: From treatment baseline through study completion, up to 24 years
Hospitalisations
Number and proportion of participants with hospitalisations recorded in routine clinical data.
Time frame: From treatment baseline through study completion, up to 24 years
Malignancies and secondary autoimmune diseases
Number and proportion of participants with malignancies or secondary autoimmune diseases recorded during follow-up.
Time frame: From treatment baseline through study completion, up to 24 years
Changes in routine laboratory parameters
Change from baseline in routinely collected laboratory parameters, including white blood cell count and immunoglobulin levels, where available.
Time frame: From treatment baseline through study completion, up to 24 years
Plan to share: Yes — De-identified individual participant data underlying the results reported in publications may be made available, subject to applicable ethical approvals, data protection requirements, study governance processes, and a data-sharing agreement.
Supporting information: Study protocol, Statistical analysis plan
Time frame: Beginning after publication of the primary study results and continuing for a period determined by the study management group and applicable institutional data-retention requirements.
Access criteria: Requests from qualified researchers with a methodologically sound proposal will be considered by the study management group on a case-by-case basis. Access will be subject to appropriate approvals, participant consent where applicable, data protection requirements, and execution of a data-sharing agreement.
Started Oct 2026 (actual). Primary completion is estimated for Dec 2032, 74 months after the start.
Of 334 non-industry observational studies under Multiple Sclerosis, half reached primary completion within 36 months of starting (the median), counting those still running; a quarter within 13 and three quarters within 73. This study's planned 74 months is above that.
Counting every sponsor, half of 425 studies reached it within 41 months; a quarter within 15 and three quarters within 75.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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