Clinical trial NCT03193866: COMparison Between All immunoTherapies for Multiple Sclerosis.
Official 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Relapsing-remitting Multiple Sclerosis
Keywords: Immunomodulating treatment
Cohort study
Dimethyl fumarate
Fingolimod
Interferon-beta
Natalizumab
Rituximab
Glatiramer acetate
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
name: Kaiser Foundation Research Institute
First posted: 2017-06-21
Enrollment: 3526
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
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.

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).

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Confirmed Disease Progression in Patients With Expanded Disability Status Scale (EDSS) <2.5 at Baseline
timeFrame: 3 years
measure: Confirmed Disease Progression in Patients With EDSS ≥2.5 at Baseline
timeFrame: 3 years
measure: Disease-related Impact on Daily Life, Physical
timeFrame: 3 years
measure: Disease-related Impact on Daily Life, Psychological
timeFrame: 3 years
Secondary outcomes:
measure: Annualized Relapse Rate
timeFrame: 3 years
measure: Remaining on Drug
timeFrame: 3 years
measure: Increase in EDSS
timeFrame: 3 years
measure: Proportion of Patients With at Least 1 Step Increase in EDSS
timeFrame: 3 years
measure: Proportion of Patients With No Evidence of Disease Activity (NEDA) -2
timeFrame: 3 years
measure: Proportion of Patients With NEDA-3
timeFrame: 3 years
measure: Quality of Life Assessments
timeFrame: 3 years
measure: Fatigue
timeFrame: 3 years
measure: Treatment Satisfaction
timeFrame: 3 years
measure: Rate of Serious Infections
timeFrame: 3 years
measure: Rate of Major Adverse Cardiovascular Events (MACE)
timeFrame: 3 years
measure: Rate of Invasive Cancer
timeFrame: 3 years
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Fredrik Piehl
Study officials:
affiliation: Karolinska Institutet
name: Fredrik Piehl, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska Institutet
name: Anders Svenningsson, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska Institutet
name: Anna Fogdell-Hahn, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska Institutet
name: Ingrid Kockum, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska Institutet
name: Thomas Frisell, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kaiser Permanent Southern California, Los Angeles, USA
name: Annette Langer-Gould, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: