Multiple SclerosisREAL-MSNCT07899502
REAL-MS: Observational Database Study of AHSCT and MS Therapies
An observational study of Multiple Sclerosis and Multiple Sclerosis (MS) - Relapsing-remitting, run by Imperial College London at 3 sites in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Sclerosis, Multiple Sclerosis (MS) - Relapsing-remitting, Multiple Sclerosis (MS) Primary Progressive
- What is being tested?
- Autologous haematopoietic stem cell transplantation (AHSCT) and High-efficacy disease-modifying therapy (HE-DMT)
- Type of treatment
- Surgery or procedure
- How many people
- 2,000 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- 7 Oct 2026to 31 Dec 2032
- How long will I take part?
- 5 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 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: * Imperial College Healthcare NHS Trust, * The Queen Square MS Centre at University College London Hospitals NHS; * Foundation Trust, and King's College Hospital NHS Foundation Trust. 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.
Who may be able to join
- Diagnosis of MS according to the appropriate diagnostic criteria at the time of diagnosis;
- Age ≥ 18 years old at the time of the inclusion in the study;
- Treatment with AHSCT or a H-E DMT at a participating centre. Eligible H-E DMTs will include anti-CD20 monoclonal antibodies, natalizumab, alemtuzumab, cladribine, and other therapies approved by the study management group during the study period;
- Availability of a minimum required baseline dataset as defined in the study case report form and data dictionary;
- Availability of at least one post-baseline clinical assessment, unless the patient is included in safety analyses only;
- For participation in the prospective phase of the study, capacity to provide informed consent, as judged by the investigator, and provision of written informed consent where required by applicable local regulations and ethics approvals;
Who cannot join
- Age <18 years at the time of study inclusion;
- Insufficient baseline data to confirm eligibility, treatment exposure, or key study variables;
- No post-baseline follow-up data, unless the participant is included in safety analyses only;
- Concurrent participation in an interventional randomised controlled trial where inclusion in the study would conflict with the trial protocol or compromise interpretation of study outcomes;
- Lack of informed consent for prospective participation
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom3 sites, 3 recruiting
- Recruiting
Imperial College Healthcare NHS Trust
London
Richard Nicholas, MD, PhD, 020 3311 1234, richard.nicholas3@nhs.net
Antonio Scalfari, MD, PhD
- Not yet recruiting
King's College Hospital NHS Foundation Trust
London
Yasser Falah, MD, y.falah@nhs.net
Yasser Falah, MD
- Not yet recruiting
University College London Hospitals NHS Foundation Trust
London
Olga Ciccarelli, MD, olga.ciccarelli@nhs.net
Olga Ciccarelli, MD
About this study
Official title: Real-World Effectiveness and Safety of Autologous Haematopoietic Stem Cell Transplantation and Other Therapeutic Strategies in Multiple Sclerosis (REAL-MS) - An Observational Database Study
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.
Read the detailed description
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.
- Conditions
- Multiple Sclerosis, Multiple Sclerosis (MS) - Relapsing-remitting, Multiple Sclerosis (MS) Primary Progressive
- Being tested
- Autologous haematopoietic stem cell transplantation (AHSCT), High-efficacy disease-modifying therapy (HE-DMT)
- Keywords
- autologous haematopoietic stem cell transplant, AHSCT, ocrelizumab, ofatumumab, ublituximab, natalizumab, cladribine, alemtuzumab
- Medical subject headings
- Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Chronic Progressive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous haematopoietic stem cell transplantation (AHSCT)Procedure or surgery
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.
High-efficacy disease-modifying therapy (HE-DMT)Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Autologous haematopoietic stem cell transplantation (AHSCT) | Adults with multiple sclerosis treated with autologous haematopoietic stem cell transplantation as part of routine clinical care. Receives: Procedure: Autologous haematopoietic stem cell transplantation (AHSCT) | |
| High-efficacy disease-modifying therapies (HE-DMTs) | 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. Receives: Drug: High-efficacy disease-modifying therapy (HE-DMT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From treatment baseline through study completion, up to 24 years
Secondary outcomes (13)
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.
Measured: From treatment baseline through study completion, up to 24 years
Annualised relapse rate
Number of clinical relapses per participant-year of follow-up.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From treatment baseline through study completion, up to 24 years
Time to first clinical relapse
Time from treatment baseline to the first clinical relapse.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From treatment baseline through study completion, up to 24 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2026
- Study start7 Oct 2026
- Primary completion31 Dec 2032 (estimated)
- Study completion31 Dec 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 2,000 participants (estimated)
- Target duration
- 5 Years
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Imperial College Healthcare NHS Trust, University College London Hospitals, King's College Hospital NHS Trust
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07899502
- Sponsor's protocol ID
- 209423
- Other IDs
- 374846
- Acronym
- REAL-MS
- Status last verified
- Oct 2026
- First submitted
- 12 Oct 2026
- Last updated
- 27 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.
Publications
Kalincik T, Sharmin S, Roos I, Freedman MS, Atkins H, Burman J, Massey J, Sutton I, Withers B, Macdonell R, Grigg A, Torkildsen O, Bo L, Lehmann AK, Havrdova EK, Krasulova E, Trneny M, Kozak T, van der Walt A, Butzkueven H, McCombe P, Skibina O, Lechner-Scott J, Willekens B, Cartechini E, Ozakbas S, Alroughani R, Kuhle J, Patti F, Duquette P, Lugaresi A, Khoury SJ, Slee M, Turkoglu R, Hodgkinson S, John N, Maimone D, Sa MJ, van Pesch V, Gerlach O, Laureys G, Van Hijfte L, Karabudak R, Spitaleri D, Csepany T, Gouider R, Castillo-Trivino T, Taylor B, Sharrack B, Snowden JA; MSBase Study Group Collaborators; MSBase Study Group Authors; Mrabet S, Garber J, Sanchez-Menoyo JL, Aguera-Morales E, Blanco Y, Al-Asmi A, Weinstock-Guttman B, Fragoso Y, de Gans K, Kermode A; MSBase Study Group. Comparative Effectiveness of Autologous Hematopoietic Stem Cell Transplant vs Fingolimod, Natalizumab, and Ocrelizumab in Highly Active Relapsing-Remitting Multiple Sclerosis. JAMA Neurol. 2023 Jul 1;80(7):702-713. doi: 10.1001/jamaneurol.2023.1184.
PubMed 37437240Kalincik T, Sharmin S, Roos I, Freedman MS, Atkins H, Massey J, Sutton I, Withers B, Burman J, Torkildsen O, Bo L, Lehmann AK, Havrdova EK, Krasulova E, Trneny M, Kozak T, Macdonell R, Brown JWL, Coles A, van der Walt A, Butzkueven H, Van Wijmeersch B, Lechner-Scott J, Barnett M, Laureys G, Willekens B, Buzzard K, Skibina O, Di Gregorio M, Hodgkinson S, Ozakbas S, Meca-Lallana JE, Alroughani R, Prevost J, Foschi M, Surcinelli A, Neri S, Eichau S, McCombe P, John N, Cardenas-Robledo S, Oh J, Sanchez-Menoyo JL, Patti F, Gerlach O, Blanco Y, Grammond P, Sharrack B, Snowden JA. Haematopoietic stem cell transplant versus immune-reconstitution therapy in relapsing multiple sclerosis. Brain. 2026 Mar 5;149(3):951-962. doi: 10.1093/brain/awaf286.
PubMed 40755195Zhukovsky C, Sandgren S, Silfverberg T, Einarsdottir S, Tolf A, Landtblom AM, Novakova L, Axelsson M, Malmestrom C, Cherif H, Carlson K, Lycke J, Burman J. Autologous haematopoietic stem cell transplantation compared with alemtuzumab for relapsing-remitting multiple sclerosis: an observational study. J Neurol Neurosurg Psychiatry. 2021 Feb;92(2):189-194. doi: 10.1136/jnnp-2020-323992. Epub 2020 Oct 26.
PubMed 33106366Boffa G, Lapucci C, Sbragia E, Varaldo R, Raiola AM, Curro D, Roccatagliata L, Capello E, Laroni A, Mikulska M, Gualandi F, Uccelli A, Angelucci E, Mancardi GL, Inglese M. Aggressive multiple sclerosis: a single-centre, real-world treatment experience with autologous haematopoietic stem cell transplantation and alemtuzumab. Eur J Neurol. 2020 Oct;27(10):2047-2055. doi: 10.1111/ene.14324. Epub 2020 Jun 16.
PubMed 32418281Muraro PA, Zito A, Signori A, Sormani MP, Rigoni E, Pollidoro F, Bergamaschi R, Mariottini A, Malik O, Nandoskar A, Singh-Curry V, Mehra V, Kazmi M, Gabriel I, Silber E, Nicholas R, Scalfari A. Effectiveness of Autologous Hematopoietic Stem Cell Transplantation versus Alemtuzumab and Ocrelizumab in Relapsing Multiple Sclerosis: A Single Center Cohort Study. Ann Neurol. 2025 Aug;98(2):294-307. doi: 10.1002/ana.27247. Epub 2025 Apr 19.
PubMed 40251896Burt RK, Balabanov R, Burman J, Sharrack B, Snowden JA, Oliveira MC, Fagius J, Rose J, Nelson F, Barreira AA, Carlson K, Han X, Moraes D, Morgan A, Quigley K, Yaung K, Buckley R, Alldredge C, Clendenan A, Calvario MA, Henry J, Jovanovic B, Helenowski IB. Effect of Nonmyeloablative Hematopoietic Stem Cell Transplantation vs Continued Disease-Modifying Therapy on Disease Progression in Patients With Relapsing-Remitting Multiple Sclerosis: A Randomized Clinical Trial. JAMA. 2019 Jan 15;321(2):165-174. doi: 10.1001/jama.2018.18743.
PubMed 30644983Mancardi GL, Sormani MP, Gualandi F, Saiz A, Carreras E, Merelli E, Donelli A, Lugaresi A, Di Bartolomeo P, Rottoli MR, Rambaldi A, Amato MP, Massacesi L, Di Gioia M, Vuolo L, Curro D, Roccatagliata L, Filippi M, Aguglia U, Iacopino P, Farge D, Saccardi R; ASTIMS Haemato-Neurological Collaborative Group, On behalf of the Autoimmune Disease Working Party (ADWP) of the European Group for Blood and Marrow Transplantation (EBMT); ASTIMS Haemato-Neurological Collaborative Group On behalf of the Autoimmune Disease Working Party ADWP of the European Group for Blood and Marrow Transplantation EBMT. Autologous hematopoietic stem cell transplantation in multiple sclerosis: a phase II trial. Neurology. 2015 Mar 10;84(10):981-8. doi: 10.1212/WNL.0000000000001329. Epub 2015 Feb 11.
PubMed 25672923Muraro PA, Mariottini A, Greco R, Burman J, Iacobaeus E, Inglese M, Snowden JA, Alexander T, Amato MP, Bo L, Boffa G, Ciccarelli O, Cohen JA, Derfuss T, Farge D, Freedman MS, Gaughan M, Heesen C, Kazmi M, Kirzigov K, Ljungman P, Mancardi G, Martin R, Mehra V, Moiola L, Saccardi R, Tintore M, Stankoff B, Sharrack B; Attendees of the ECTRIMS Focused Workshop on HSCT. Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder - recommendations from ECTRIMS and the EBMT. Nat Rev Neurol. 2025 Mar;21(3):140-158. doi: 10.1038/s41582-024-01050-x. Epub 2025 Jan 15.
PubMed 39814869Muraro PA, Martin R, Mancardi GL, Nicholas R, Sormani MP, Saccardi R. Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis. Nat Rev Neurol. 2017 Jul;13(7):391-405. doi: 10.1038/nrneurol.2017.81. Epub 2017 Jun 16.
PubMed 28621766
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Real-World Effectiveness and Safety of Autologous Haematopoietic Stem Cell Transplantation and Other Therapeutic Strategies in Multiple Sclerosis (REAL-MS) - An Observational Database Study
- ClinicalTrials.gov ID
- NCT07899502
- Acronym / sponsor ID
- REAL-MS / 209423
- Conditions
- Multiple Sclerosis, Multiple Sclerosis (MS) - Relapsing-remitting, Multiple Sclerosis (MS) Primary Progressive
- Keywords
- autologous haematopoietic stem cell transplant, AHSCT, ocrelizumab, ofatumumab, ublituximab, natalizumab, cladribine, alemtuzumab
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 2,000 participants (estimated)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Imperial College Healthcare NHS Trust, University College London Hospitals, King's College Hospital NHS Trust
- Study start
- 7 Oct 2026 (actual)
- Primary completion
- 31 Dec 2032 (estimated)
- Study completion
- 31 Dec 2032 (estimated)
- First posted
- 27 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Target follow-up
- 5 Years
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Autologous haematopoietic stem cell transplantation (AHSCT) | – | Procedure: Autologous haematopoietic stem cell transplantation (AHSCT)Adults with multiple sclerosis treated with autologous haematopoietic stem cell transplantation as part of routine clinical care. |
| High-efficacy disease-modifying therapies (HE-DMTs) | – | Drug: High-efficacy disease-modifying therapy (HE-DMT)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 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: * Imperial College Healthcare NHS Trust, * The Queen Square MS Centre at University College London Hospitals NHS; * Foundation Trust, and King's College Hospital NHS Foundation Trust. 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.
Key inclusion criteria (6 listed)
- Diagnosis of MS according to the appropriate diagnostic criteria at the time of diagnosis;
- Age ≥ 18 years old at the time of the inclusion in the study;
- Treatment with AHSCT or a H-E DMT at a participating centre. Eligible H-E DMTs will include anti-CD20 monoclonal antibodies, natalizumab, alemtuzumab, cladribine, and other therapies approved by the study management group during the study period;
- Availability of a minimum required baseline dataset as defined in the study case report form and data dictionary;
- Availability of at least one post-baseline clinical assessment, unless the patient is included in safety analyses only;
Key exclusion criteria (5 listed)
- Age <18 years at the time of study inclusion;
- Insufficient baseline data to confirm eligibility, treatment exposure, or key study variables;
- No post-baseline follow-up data, unless the participant is included in safety analyses only;
- Concurrent participation in an interventional randomised controlled trial where inclusion in the study would conflict with the trial protocol or compromise interpretation of study outcomes;
- Lack of informed consent for prospective participation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autologous haematopoietic stem cell transplantation (AHSCT)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. | Procedure or surgery | Autologous haematopoietic stem cell transplantation (AHSCT) |
| High-efficacy disease-modifying therapy (HE-DMT)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. | Drug | High-efficacy disease-modifying therapies (HE-DMTs) |
Primary outcome
No Evidence of Disease Activity (NEDA-3)
Time frame: From treatment baseline through study completion, up to 24 years
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.
13 secondary outcomes
Absence of clinical relapses
Time frame: From treatment baseline through study completion, up to 24 years
Annualised relapse rate
Time frame: From treatment baseline through study completion, up to 24 years
Absence of MRI activity
Time frame: From treatment baseline through study completion, up to 24 years
Absence of 6-month confirmed disability progression (CDP)
Time frame: From treatment baseline through study completion, up to 24 years
Absence of progression independent of relapse activity (PIRA)
Time frame: From treatment baseline through study completion, up to 24 years
Probability of 6-month confirmed disability improvement (CDI)
Time frame: From treatment baseline through study completion, up to 24 years
Time to first clinical relapse
Time frame: From treatment baseline through study completion, up to 24 years
Time to first MRI activity
Time frame: From treatment baseline through study completion, up to 24 years
Time to 6-month confirmed disability progression
Time frame: From treatment baseline through study completion, up to 24 years
Time to progression independent of relapse activity
Time frame: From treatment baseline through study completion, up to 24 years
Time to treatment discontinuation or switch
Time frame: From treatment baseline through study completion, up to 24 years
Serious adverse events
Time frame: From treatment baseline through study completion, up to 24 years
Mortality
Time frame: From treatment baseline through study completion, up to 24 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2026.
- Background: PubMed 37437240Kalincik T, Sharmin S, Roos I, Freedman MS, Atkins H, Burman J, Massey J, Sutton I, Withers B, Macdonell R, Grigg A, Torkildsen O, Bo L, Lehmann AK, Havrdova EK, Krasulova E, Trneny M, Kozak T, van der Walt A, Butzkueven H, McCombe P, Skibina O, Lechner-Scott J, Willekens B, Cartechini E, Ozakbas S, Alroughani R, Kuhle J, Patti F, Duquette P, Lugaresi A, Khoury SJ, Slee M, Turkoglu R, Hodgkinson S, John N, Maimone D, Sa MJ, van Pesch V, Gerlach O, Laureys G, Van Hijfte L, Karabudak R, Spitaleri D, Csepany T, Gouider R, Castillo-Trivino T, Taylor B, Sharrack B, Snowden JA; MSBase Study Group Collaborators; MSBase Study Group Authors; Mrabet S, Garber J, Sanchez-Menoyo JL, Aguera-Morales E, Blanco Y, Al-Asmi A, Weinstock-Guttman B, Fragoso Y, de Gans K, Kermode A; MSBase Study Group. Comparative Effectiveness of Autologous Hematopoietic Stem Cell Transplant vs Fingolimod, Natalizumab, and Ocrelizumab in Highly Active Relapsing-Remitting Multiple Sclerosis. JAMA Neurol. 2023 Jul 1;80(7):702-713. doi: 10.1001/jamaneurol.2023.1184.
- Background: PubMed 40755195Kalincik T, Sharmin S, Roos I, Freedman MS, Atkins H, Massey J, Sutton I, Withers B, Burman J, Torkildsen O, Bo L, Lehmann AK, Havrdova EK, Krasulova E, Trneny M, Kozak T, Macdonell R, Brown JWL, Coles A, van der Walt A, Butzkueven H, Van Wijmeersch B, Lechner-Scott J, Barnett M, Laureys G, Willekens B, Buzzard K, Skibina O, Di Gregorio M, Hodgkinson S, Ozakbas S, Meca-Lallana JE, Alroughani R, Prevost J, Foschi M, Surcinelli A, Neri S, Eichau S, McCombe P, John N, Cardenas-Robledo S, Oh J, Sanchez-Menoyo JL, Patti F, Gerlach O, Blanco Y, Grammond P, Sharrack B, Snowden JA. Haematopoietic stem cell transplant versus immune-reconstitution therapy in relapsing multiple sclerosis. Brain. 2026 Mar 5;149(3):951-962. doi: 10.1093/brain/awaf286.
- Background: PubMed 33106366Zhukovsky C, Sandgren S, Silfverberg T, Einarsdottir S, Tolf A, Landtblom AM, Novakova L, Axelsson M, Malmestrom C, Cherif H, Carlson K, Lycke J, Burman J. Autologous haematopoietic stem cell transplantation compared with alemtuzumab for relapsing-remitting multiple sclerosis: an observational study. J Neurol Neurosurg Psychiatry. 2021 Feb;92(2):189-194. doi: 10.1136/jnnp-2020-323992. Epub 2020 Oct 26.
- Background: PubMed 32418281Boffa G, Lapucci C, Sbragia E, Varaldo R, Raiola AM, Curro D, Roccatagliata L, Capello E, Laroni A, Mikulska M, Gualandi F, Uccelli A, Angelucci E, Mancardi GL, Inglese M. Aggressive multiple sclerosis: a single-centre, real-world treatment experience with autologous haematopoietic stem cell transplantation and alemtuzumab. Eur J Neurol. 2020 Oct;27(10):2047-2055. doi: 10.1111/ene.14324. Epub 2020 Jun 16.
- Background: PubMed 40251896Muraro PA, Zito A, Signori A, Sormani MP, Rigoni E, Pollidoro F, Bergamaschi R, Mariottini A, Malik O, Nandoskar A, Singh-Curry V, Mehra V, Kazmi M, Gabriel I, Silber E, Nicholas R, Scalfari A. Effectiveness of Autologous Hematopoietic Stem Cell Transplantation versus Alemtuzumab and Ocrelizumab in Relapsing Multiple Sclerosis: A Single Center Cohort Study. Ann Neurol. 2025 Aug;98(2):294-307. doi: 10.1002/ana.27247. Epub 2025 Apr 19.
- Results publication: PubMed 30644983Burt RK, Balabanov R, Burman J, Sharrack B, Snowden JA, Oliveira MC, Fagius J, Rose J, Nelson F, Barreira AA, Carlson K, Han X, Moraes D, Morgan A, Quigley K, Yaung K, Buckley R, Alldredge C, Clendenan A, Calvario MA, Henry J, Jovanovic B, Helenowski IB. Effect of Nonmyeloablative Hematopoietic Stem Cell Transplantation vs Continued Disease-Modifying Therapy on Disease Progression in Patients With Relapsing-Remitting Multiple Sclerosis: A Randomized Clinical Trial. JAMA. 2019 Jan 15;321(2):165-174. doi: 10.1001/jama.2018.18743.
- Results publication: PubMed 25672923Mancardi GL, Sormani MP, Gualandi F, Saiz A, Carreras E, Merelli E, Donelli A, Lugaresi A, Di Bartolomeo P, Rottoli MR, Rambaldi A, Amato MP, Massacesi L, Di Gioia M, Vuolo L, Curro D, Roccatagliata L, Filippi M, Aguglia U, Iacopino P, Farge D, Saccardi R; ASTIMS Haemato-Neurological Collaborative Group, On behalf of the Autoimmune Disease Working Party (ADWP) of the European Group for Blood and Marrow Transplantation (EBMT); ASTIMS Haemato-Neurological Collaborative Group On behalf of the Autoimmune Disease Working Party ADWP of the European Group for Blood and Marrow Transplantation EBMT. Autologous hematopoietic stem cell transplantation in multiple sclerosis: a phase II trial. Neurology. 2015 Mar 10;84(10):981-8. doi: 10.1212/WNL.0000000000001329. Epub 2015 Feb 11.
- Results publication: PubMed 39814869Muraro PA, Mariottini A, Greco R, Burman J, Iacobaeus E, Inglese M, Snowden JA, Alexander T, Amato MP, Bo L, Boffa G, Ciccarelli O, Cohen JA, Derfuss T, Farge D, Freedman MS, Gaughan M, Heesen C, Kazmi M, Kirzigov K, Ljungman P, Mancardi G, Martin R, Mehra V, Moiola L, Saccardi R, Tintore M, Stankoff B, Sharrack B; Attendees of the ECTRIMS Focused Workshop on HSCT. Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder - recommendations from ECTRIMS and the EBMT. Nat Rev Neurol. 2025 Mar;21(3):140-158. doi: 10.1038/s41582-024-01050-x. Epub 2025 Jan 15.
- Results publication: PubMed 28621766Muraro PA, Martin R, Mancardi GL, Nicholas R, Sormani MP, Saccardi R. Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis. Nat Rev Neurol. 2017 Jul;13(7):391-405. doi: 10.1038/nrneurol.2017.81. Epub 2017 Jun 16.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
University College London Hospitals NHS Foundation Trust
London, United Kingdom
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Multiple Sclerosis and Multiple Sclerosis (MS) - Relapsing-remitting, run by Imperial College London at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
No Evidence of Disease Activity (NEDA-3) (time frame: From treatment baseline through study completion, up to 24 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07899502, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2026.