COMparison Between All immunoTherapies for Multiple Sclerosis.

Completed

Conditions: Relapsing-remitting Multiple Sclerosis

Registration Number: NCT03193866

Lead Sponsor: Karolinska Institutet

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 3526

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Confirmed Disease Progression in Patients With Expanded Disability Status Scale (EDSS) <2.5 at Baseline	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).
Confirmed Disease Progression in Patients With EDSS ≥2.5 at Baseline	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).
Disease-related Impact on Daily Life, Physical	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.
Disease-related Impact on Daily Life, Psychological	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 Outcome Measures

Name	Time	Method
Rate of Serious Infections	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
Rate of Major Adverse Cardiovascular Events (MACE)	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
Annualized Relapse Rate	3 years	- Comparison of mean number of relapses per year between the different treatments
Remaining on Drug	3 years	- Proportion remaining on the index DMT after 3 years
Proportion of Patients With No Evidence of Disease Activity (NEDA) -2	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.
Quality of Life Assessments	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.
Increase in EDSS	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).
Proportion of Patients With at Least 1 Step Increase in EDSS	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).
Proportion of Patients With NEDA-3	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.
Fatigue	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.
Treatment Satisfaction	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.
Rate of Invasive Cancer	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.