Relapsing-Remitting Multiple Sclerosis
Conditions
Keywords
disease progression, Multiple Sclerosis, disease activity, Tysabri, natalizumab, long-term safety
Brief summary
The primary objective of this study is to assess the long-term safety and impact on disease activity and progression of Tysabri in participants with relapsing remitting multiple sclerosis (RRMS) in a clinical practice setting.
Detailed description
TOP is an epidemiological observational study of participants receiving natalizumab, with each participant to be followed for up to 15 years. This study is designed to address the long-term safety profile and the long-term impact on disease activity and progression of Tysabri with marketed use, and the impact of treatment on disability in particular by comparing the results with prospectively determined controls from established databases.
Interventions
DRUGTysabri
According to the local prescribing information
Sponsors
Biogen
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Documented diagnosis of Relapsing Remitting Multiple Sclerosis * The decision to treat with Tysabri must precede enrollment * Patient must be a new Tysabri user, and must not have had more than 3 Tysabri infusions prior to enrollment * Must have had at least one relapse in the previous year, and must satisfy locally approved therapeutic indications for Tysabri Key
Exclusion criteria
* History of Progressive Multifocal Leukoencephalopathy or other opportunistic infections, or an increased risk of opportunistic infections * History of positive anti-Tysabri antibodies * Concomitant Immunomodulatory or immunosuppressive therapy during therapy with Tysabri * Patient immunocompromised at the time of enrollment * Known active malignancy * Women must not be breast feeding or pregnant, or planning to become pregnant (must use birth control unless surgically sterile) NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants with Serious Adverse Events (SAE) | Up to 15 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Distribution of the Total Number of Relapses | Yearly for up to 15 years | — |
| Time to First Relapse | Yearly for up to 15 years | — |
| Percentage of Participants with Relapse | Yearly for up to 15 years | — |
| Percentage of Participants with Disability Progression | Yearly for up to 15 years | Disability progression is defined as at least a 1.0 point increase on the Expanded Disability Status Scale (EDSS) from Baseline that is sustained over 6 months. The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist. |
| Annualized Relapse Rate (ARR) | Yearly for up to 15 years | A clinical relapse is defined as new or recurrent neurological symptoms, not associated with fever, lasting for at least 24 hours, and followed by a period of 30 days of stability or improvement. New or recurrent neurological symptoms that occur less than 30 days following the onset of a protocol-defined relapse should be considered part of the same relapse. |
| Percentage of Participants whose EDSS Worsened, Stabilized or Improved and Sustained over 6 Months | Yearly for up to 15 years | — |
| Evaluation of Baseline Disease Characteristics as Prognostic Indicators for Disease Activity and Disability Progression Over Time | Yearly for up to 15 years | Baseline disease characteristics evaluated will include: EDSS; Disease duration at baseline; Number of relapses during 1 and 2 years before baseline; Previous use of disease modifying therapy; Age, gender. |
| Evaluation of Short-Term (1 year) Disease Outcomes as Prognostic Indicators for Disease Activity and Disability Progression Over Time | Yearly for up to 15 years | Short term outcomes evaluated will include: EDSS progression during first 12 months; Occurrence of relapses during first 12 months |
| Percentage of Participants that reach Expanded Disability Status Score (EDSS) Milestones Indicating Increasing Disability | Yearly for up to 15 years | The percentage of participants that reach EDSS milestones such as 4.0, 6.0, and 7.0 sustained after 6 months. The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Czechia, Finland, France, Germany, Greece, Italy, Mexico, Netherlands, Norway, Portugal, Slovakia, Spain, United Kingdom
Outcome results
None listed