TOP: IMA-06-02 Tysabri® Observational Program

• Number of participants with serious adverse events (SAEs) [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]
  An SAE is any untoward medical occurrence that at any dose: • results in death; • in the view of the Investigator, places the patient at immediate risk of death (a life-threatening event); • requires inpatient hospitalization or prolongation of existing hospitalization; • results in persistent or significant disability/incapacity; or • results in a congenital anomaly/medically significant birth defect. MS relapses fulfilling the criteria of a SAE are not be considered SAEs for the purpose of the study.
  
  

• Annualized Relapse Rate [ Time Frame: Yearly for up to 10 years ] [ Designated as safety issue: No ]
  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.
  
  
• Distribution of the total number of relapses [ Time Frame: Yearly for up to 10 years ] [ Designated as safety issue: No ]
  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.
  
  
• Time to first relapse [ Time Frame: Yearly for up to 10 years ] [ Designated as safety issue: No ]
  
• Percentage of participants with relapse [ Time Frame: Yearly for up to 10 years ] [ Designated as safety issue: No ]
  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 with Disability Progression [ Time Frame: Yearly for up to 10 years ] [ Designated as safety issue: No ]
  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.
  
  
• Percentage of Participants that Reach Expanded Disability Status Score (EDSS) Milestones Indicating Increasing Disability [ Time Frame: Yearly for up to 10 years ] [ Designated as safety issue: No ]
  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.
  
  
• Percentage of Participants Whose Expanded Disability Status Score (EDSS) Worsened, Stabilized or Improved and Sustained over 6 Months [ Time Frame: Yearly for up to 10 years ] [ Designated as safety issue: No ]
  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.
  
  
• Evaluation of baseline disease characteristics as prognostic indicators for disease activity and disability progression over time [ Time Frame: Yearly for up to 10 years ] [ Designated as safety issue: No ]
  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 [ Time Frame: Yearly for up to 10 years ] [ Designated as safety issue: No ]
  Short term outcomes evaluated will include: • EDSS progression during first 12 months • Occurrence of relapses during first 12 months
  
  

TOP is an epidemiological observational study of participants receiving Tysabri®, with each participant to be followed for up to 10 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.