COMparison Between All immunoTherapies for Multiple Sclerosis.

NCT03193866 | Completed Results DMC FDA Drug

• 1 other identifier: COMBAT-MS
• Study Type: observational
• Target: 3,526
• Locations: 1 country
• Sites: 1

Brief Summary

The overarching goal of this study is to determine whether rituximab (RTX) offers effectiveness and safety advantages over other commonly used approved Disease-Modifying Drugs (DMT) in the largest real-world population-based structured prospective follow-up cohort of Relapsing-Remitting Multiple Sclerosis (RRMS) patients. The study will include both treatment naïve patients starting their first DMT and patients switching from a previous first line DMT (escalation/second-line).

Conditions

Relapsing-remitting Multiple Sclerosis

Keywords

Immunomodulating treatment; Cohort study; Dimethyl fumarate; Fingolimod; Interferon-beta; Natalizumab; Rituximab; Glatiramer acetate

Outcome Measures

Primary Outcomes (4)

• Confirmed Disease Progression in Patients With Expanded Disability Status Scale (EDSS) <2.5 at Baseline

  Proportion of patients with baseline EDSS \<2.5 progressing to 12 months confirmed EDSS ≥3 among those over 3 years of follow up. Expanded Disability Status Scale (EDSS) scale range: Minimum score: 0 (normal neurological examination). Maximum score: 10 (death due to multiple sclerosis) Lower scores indicate better outcomes (less disability). Higher scores indicate worse outcomes (more disability).

  3 years

• Confirmed Disease Progression in Patients With EDSS ≥2.5 at Baseline

  \- Proportion of patients with baseline EDSS ≥2.5 experiencing 12 months confirmed EDSS increase of 1 point among those over 3 years of follow up Expanded Disability Status Scale (EDSS) scale range: Minimum score: 0 (normal neurological examination). Maximum score: 10 (death due to multiple sclerosis) Lower scores indicate better outcomes (less disability). Higher scores indicate worse outcomes (more disability).

  3 years

• Disease-related Impact on Daily Life, Physical

  \- Change in the MSIS-29 physical subscale (change from baseline; mean value) The Multiple Sclerosis Impact Scale (MSIS-29) physical subscale measures patient-reported physical impact of multiple sclerosis. Scale range: Minimum score: 1 (least impact). Maximum score: 5 (highest impact). Lower scores indicate better outcomes. Higher scores indicate worse outcomes.

  3 years

• Disease-related Impact on Daily Life, Psychological

  \- Change in the MSIS-29 psychological subscale (change from baseline; mean value) The Multiple Sclerosis Impact Scale (MSIS-29) psychological subscale measures patient-reported psychological impact of multiple sclerosis. Scale range: Minimum score: 1 (least impact). Maximum score: 5 (highest impact). Lower scores indicate better outcomes. Higher scores indicate worse outcomes.

  3 years

Secondary Outcomes (12)

• Annualized Relapse Rate

  3 years

• Remaining on Drug

  3 years

• Increase in EDSS

  3 years

• Proportion of Patients With at Least 1 Step Increase in EDSS

  3 years

• Proportion of Patients With No Evidence of Disease Activity (NEDA) -2

  3 years

Interventions

Rituximab DRUG

Comparisons of efficacy and safety between rituximab and all other frequently used immunomodulating drugs against multiple sclerosis

Also known as: Natalizumab, Fingolimod, Alemtuzumab, Interferon-beta, Glatiramer acetate, Dimethyl Fumarate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All patients initiated at their first or second disease-modifying drug between January 1 2011 and June 30 2018 will be included in the trial. Up to present date, study-related data will be retrospectively controlled via individual study of patient records. Patients will be identified through the Swedish MS registry. Inclusion into the COMBAT-MS core study will be subject to written informed consent. Given the non-intervention design of the study and very limited study-specific procedures outside of clinical practise, we expect participation rates to be very high. Based on preliminary calculations from the MS registry the projected number of participants will be 3700 patients, out of which at least 1000 are treated with rituximab first or second-line.

You may qualify if:

• The study population consists of all patients with Clinically Isolated Syndrome (CIS) or RRMS who;
• Initiate a first MS DMT (treatment naïve), or Initiate a second ever DMT, of a different drug class than the first, regardless of time between drugs or reason for discontinuation("switchers") from 1st Jan 2011 to 30st June 2018, and
• Are followed at any of the University clinics of Sweden, and
• Consent to participation in COMBAT-MS core, and
• Are expected to be capable to follow study assessments.

You may not qualify if:

• \- Patients with progressive forms of MS at start of therapy are not eligible

Sponsors & Collaborators

• Karolinska Institutet: lead
• Patient-Centered Outcomes Research Institute: collaborator
• Kaiser Foundation Research Institute: collaborator

Study Sites (1)

Fredrik Piehl

Stockholm, Sweden

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum samples will be taken yearly for analysis of anti-drug antibodies. These samples will be saved in biobank. Additional blood samples will be taken for analyses of SARS-CoV-2 serologic response.

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

Rituximab; Natalizumab; Fingolimod Hydrochloride; Alemtuzumab; Interferon-beta; Glatiramer Acetate; Dimethyl Fumarate

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Humanized; Sphingosine; Amino Alcohols; Alcohols; Organic Chemicals; Propylene Glycols; Glycols; Amines; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Fumarates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids

Limitations and Caveats

COMBAT was an observational real-world study assessing the outcomes of different DMTs as used according to clinical practice. The assignment of treatments was not under investigator control, there was no randomization and no blinding of treatments. Although differences in patient characteristics at treatment start was accounted for by statistical modelling, the risk of residual confounding should be kept in mind.

Results Point of Contact

• Title: Professor Fredrik Piehl
• Organization: Karolinska Institutet

fredrik.piehl@ki.se

+46-(0)8-517 798 40

Study Officials

• Fredrik Piehl, MD, PhD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

• Anders Svenningsson, MD, PhD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

• Anna Fogdell-Hahn, PhD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

• Ingrid Kockum, PhD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

• Thomas Frisell, PhD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

• Annette Langer-Gould, MD, PhD

  Kaiser Permanent Southern California, Los Angeles, USA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Target Duration: 3 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 20, 2017
• First Posted: June 21, 2017
• Study Start: June 2, 2017
• Primary Completion: March 31, 2022
• Study Completion: March 31, 2022
• Last Updated: April 20, 2025
• Results First Posted: April 20, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)