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

Study Overview
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Brief Summary
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The aim of this retrospective study is to review and describe safety, tolerability and efficacy of Rebif® (subcutaneous interferon [IFN]-beta-1a) in children and adolescents, using information already recorded in medical records. The study duration is 13 July 2010 (first data collected) to 13 July 2011 (last data collected). In this study, Data of the subjects evaluated between 1997 and 2009 was observed.

Official Title
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Retrospective Cohort Study of Rebif® Use in Pediatric MS Patients

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Rebif®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Received one or more injections of Rebif® for treatment of a demyelinating event Be younger than 18 years of age at time of Rebif® treatment initiation Rebif® therapy must have been initiated before June 30, 2009 Exclusion Criteria: No exclusion criteria are applied

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Retrospective Cohort<br>Pediatric participants including both children (aged less than 12 years) and adolescents (aged 12 to less than 18 years) who were exposed to Rebif® for treatment of demyelinating events were observed in this retrospective cohort study. In this study, medical records of participants evaluated between 1997 to 2009 were reviewed. The observation period started with the first medical record available on site till last medical record available on site or the end of the observation period (31 December 2009), whichever occurred first. | Drug: Rebif®<br>* This is an retrospective cohort study in Pediatric participants including both children (aged less than 12 years) and adolescents (aged 12 to less than 18 years) who were exposed to Rebif® for treatment of demyelinating events (Dose regimen as per investigator's decision)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Pre-specified Medical Events | 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. | 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. | 
| Number of Participants With Serious Medical Events, and Non-serious Medical Events (Reported by the Investigator as Related to Rebif®) | 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. | 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. | 
| Number of Participants With Abnormal Laboratory Parameters | 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. | 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Medically Confirmed Clinical Relapses Rate Prior to Rebif® Initiation and During Rebif® Treatment | 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. | 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. | 
| Time to First Medically Confirmed Clinical Relapse Post-Rebif® Initiation | 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. | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Interferon beta 1a, Autoimmune Diseases, Demyelinating Diseases, Immune System Diseases, Immunologic Factors, Nervous System Diseases, Physiological Effects of Drugs, Demyelinating Autoimmune Diseases, CNS, Autoimmune Diseases of the Nervous System, Retrospective Cohort Study