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Completed

NCT Number: NCT03193866

COMparison Between All immunoTherapies for Multiple Sclerosis.

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).

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Key information

Conditions

Relapsing-Remitting Multiple Sclerosis Autoimmune Diseases Autoimmune Diseases of the Nervous System Demyelinating Autoimmune Diseases, CNS Demyelinating Diseases Immune System Diseases Multiple Sclerosis Multiple Sclerosis, Relapsing-Remitting Nervous System Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Fredrik Piehl

Stockholm, Sweden

About this study

This is a prospective non-intervention observational prospective cohort study assessing the long-term safety and efficacy of RTX treatment in MS compared with other common MS DMTs regarding both clinical and radiological parameters in a real-life population of patients with MS.

A number of parameters will be assessed annually. These include baseline demographics, previous drug history and reasons for discontinuation, disability status (expanded disability status scale), relapses, safety and adverse events (AE), contrast enhancing T1 and newly appearing T2 lesions on magnetic resonance imaging, as well as a panel of patient reported outcome measures: Symbol Digit Modalities Test (SDMT); MS impact scale-29 (MSIS-29) Fatigue Scale for Motor and Cognitive Functions (FSMC), EuroQol-5 Dimensions (EQ-5D), the MS check scale and Treatment Satisfaction Questionnaire 9 (TSQM-9).

Retrospective data entered in medical charts and the Swedish MS registry will be included together with prospective annual structured follow up from inclusion into the study for a minimum of three years (three to nine years).

In a substudy - Covid Enhancement study - analyses will be performed regarding the effect of COVID-19 on people with MS as compared to non-MS individuals and also if there is any indication that a particular DMD is associated with a risk to contract a more severe COVID-19. The analyses will primarily be performed in official health care databases.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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.

Exclusion criteria

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

Treatment and study plan

Rituximab

Drug

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

Other names: Natalizumab, Fingolimod, Alemtuzumab, Interferon-beta, Glatiramer acetate, Dimethyl Fumarate

Primary outcomes

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

    Time frame: 3 years

    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).

  2. Confirmed Disease Progression in Patients With EDSS ≥2.5 at Baseline

    Time frame: 3 years

    • 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. Disease-related Impact on Daily Life, Physical

    Time frame: 3 years

    • 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.

  4. Disease-related Impact on Daily Life, Psychological

    Time frame: 3 years

    • 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.

Secondary outcomes

  1. Annualized Relapse Rate

    Time frame: 3 years

    • Comparison of mean number of relapses per year between the different treatments

  2. Remaining on Drug

    Time frame: 3 years

    • Proportion remaining on the index DMT after 3 years

  3. Increase in EDSS

    Time frame: 3 years

    • Comparison of yearly increase in mean EDSS between the different treatments

    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).

  4. Proportion of Patients With at Least 1 Step Increase in EDSS

    Time frame: 3 years

    • Comparison of yearly proportion of patients with at least 1 step increase in EDSS between the different treatments

    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).

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

    Time frame: 3 years

    • Comparison of yearly proportion of patients with No Evidence of Disease Activity (NEDA) -2 (free of exacerbations, new/enlarged T2-lesions and occurrence of CEL) between the treatments.

    Lower NEDA-2 scores indicate better outcomes. Higher NEDA-2 scores indicate worse outcomes.

  6. Proportion of Patients With NEDA-3

    Time frame: 3 years

    • Comparison of yearly proportion of patients with NEDA-3 (NEDA-2 plus no confirmed worsening of EDSS from baseline).

    Lower NEDA-3 scores indicate better outcomes. Higher NEDA-3 scores indicate worse outcomes.

  7. Quality of Life Assessments

    Time frame: 3 years

    Comparison of health-related quality of life measured by the European Quality of Life Five Dimensions (EQ-5D). Higher values indicate better health, and lower values indicate poorer health. The maximum theoretical value is 1. While there is no fixed minimum, scores can fall below 0, indicating health states worse than death. In this study, scores ranged from -0.59 to 1, which represent clinically relevant ranges of values.

  8. Fatigue

    Time frame: 3 years

    Comparison of fatigue measured by the Fatigue Scale for Motor and Cognitive Functions (FSMC).

    The fatigue scale for motor and cognitive functions (FSMC) scale range: Minimum score: 20. Maximum score: 100. Lower scores indicate better outcomes. Higher scores indicate worse outcomes.

  9. Treatment Satisfaction

    Time frame: 3 years

    Comparison of patient satisfaction with their treatment using the Treatment Satisfaction Questionnaire (TSQ), items 1-9, restricted to patients remaining on index DMT at 3 years.

    The Treatment Satisfaction Questionnaire (TSQ), items 1-9 scale range: Minimum score: 0. Maximum score: 100. Lower scores indicate worse outcomes. Higher scores indicate better outcomes.

  10. Rate of Serious Infections

    Time frame: 3 years

    • Rate of serious infections, defined as hospitalizations where the main diagnosis included an ICD-10 diagnosis code in the national patient register in the 3 years after initiating index DMT

  11. Rate of Major Adverse Cardiovascular Events (MACE)

    Time frame: 3 years

    • Rate of MACE, defined as acute coronary syndrome, stroke or death from any cardiovascular cause based on corresponding ICD-codes in the national patient and cause of death registries in the 3 years after initiating index DMT

  12. Rate of Invasive Cancer

    Time frame: 3 years

    • Rate of incident invasive cancer, defined as invasive cancers based on corresponding ICD-codes in the national cancer registry in the 3 years after initiating index DMT.

Sponsors and collaborators

Lead sponsor

Karolinska Institutet

Other

Collaborators

  • Kaiser Foundation Research Institute
  • Patient-Centered Outcomes Research Institute

Registry information

Official study title

COMparison Between All immunoTherapies for Multiple Sclerosis. An Observational Long-term Prospective Cohort Study of Safety, Efficacy and Patient's Satisfaction of MS Disease Modulatory Treatments in Relapsing-remitting Multiple Sclerosis

Acronym: COMBAT-MS

Important dates

Study start
2017
Primary completion
2022
Study completion
2022
First posted
Jun 21, 2017
Registry last updated
Apr 20, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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