Retrospective Cohort Study of Rebif® Use in Pediatric Multiple Sclerosis (MS) Subjects (REPLAY)

Laboratory parameters assessed for abnormality were: total white blood cell count (Neutrophils, Lymphocytes, Leukocytes, Monocytes, Eosinophils and Basophils), differential hematogram (Hematocrit, Erythrocytes, Hemoglobin, and Platelet), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and thyroid tests (including Triiodothyronine, Thyroxine, Thyroperoxidase Antibody and Thyroid-Stimulating Hormone). Due to the retrospective nature of the study, laboratory data should be interpreted with caution as data were not collected according to a specific time schedule and the time on study per participant was not standardized.

Time frame: Start of observation period (first medical record available on site) up to last medical record available on site or the end of the observation period (31 December 2009), whichever occurred first.

Population: Total analysis set included all the participants who were exposed to Rebif® for treatment of demyelinating event and were evaluated in this retrospective study. 'n' signifies number of participants who were evaluable for the specified categories.

These pre-specified medical events categories were evaluated: injections site reactions, flu-like symptoms, hepatic disorders, blood cell disorders, allergic reactions, epilepsy and convulsive disorders, thyroid dysfunction, autoimmune diseases, bone/epiphyseal and cartilage disorders, serious infections, malignancies. Each category defined by group of events which best fit the medical concept either using a standard medical dictionary for regulatory activities (MedDRA) Query (SMQ) e.g., Malignancies was defined by the SMQ Malignancies (narrow scope) containing more than 1800 different preferred terms (PTs) (including procedures and lab tests) or using a customized query, e.g., Serious infections was defined by all PTs assessed as serious in System Organ Class (SOC) Infections and Infestation. Participants may be represented in more than once in a category (Participants could have reported several medicals events pertaining to a specific category) as well as in more than one category.

Time frame: Start of observation period (first medical record available on site) up to last medical record available on site or the end of the observation period (31 December 2009), whichever occurred first.

Population: Total analysis set included all the participants who were exposed to Rebif® for treatment of demyelinating event and were evaluated in this retrospective study.

Medical events in the retrospective study are equivalent to adverse events in a prospective clinical study. A medical event was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an investigational medicinal product (IMP), regardless of causal relationship and even if no IMP has been administered. Serious medical event: A medical event that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. Participants may be represented in more than one category as participant who had experienced serious medical event may also had experienced non-serious medical event reported by the Investigator as related to Rebif®, so in that case it will be counted in both the categories.

Time frame: Start of observation period (first medical record available on site) up to last medical record available on site or the end of the observation period (31 December 2009), whichever occurred first.

Population: Total analysis set included all the participants who were exposed to Rebif® for treatment of demyelinating event and were evaluated in this retrospective study.

Medically confirmed clinical relapses were defined as the emergence of new neurological symptoms that occurred more than 30 days after a previous attack and persisted for more than or equal to 24 hours in the absence of known inter-current illness. Annualized relapse rate was defined as number of attacks per year.

Time frame: Start of observation period (first medical record available on site) up to last medical record available on site or the end of the observation period (31 December 2009), whichever occurred first.

Population: Multiple sclerosis (MS) analysis set is a subset of the Retrospective Cohort set included all participants with a final diagnosis of MS. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.

Medically confirmed clinical relapses were defined as the emergence of new neurological symptoms that occurred more than 30 days after a previous attack and persisted for more than or equal to 24 hours in the absence of known inter-current illness.

Time frame: Start of observation period (first medical record available on site) up to last medical record available on site or the end of the observation period (31 December 2009), whichever occurred first.

Population: Multiple sclerosis (MS) analysis set is a subset of the Retrospective Cohort set included all participants with a final diagnosis of MS. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.