A Study of Rebif® in Subjects With Relapsing Multiple Sclerosis

The MSTCQ was used as a tool to measure treatment satisfaction, focusing on the attributes specific to multiple sclerosis (MS) medications. The FLS subscale of MSTCQ was defined as the sum of the scores for questions 13 to 16 with a minimum possible total FLS score = 1 and a maximum possible total FLS score = 20. Lower score indicates lower flu like symptoms and better satisfaction. Difference between Rebif Morning Administration and Rebif Evening Administration groups at Week 12 is presented in statistical analysis section.

The MSTCQ was used as a tool to measure treatment satisfaction, focusing on the attributes specific to multiple sclerosis (MS) medications. The FLS subscale of MSTCQ was defined as the sum of the scores for questions 13 to 16 with a minimum possible total FLS score = 1 and a maximum possible total FLS score = 20. Lower score indicates lower flu like symptoms and better satisfaction. Difference between Rebif Morning Administration and Rebif Evening Administration groups at Week 4 and 8 is presented in statistical analysis section.

MSTCQ was used as a tool to measure treatment satisfaction, focusing on attributes specific to MS medications. Following sub-scales were assessed: Injection site reactions (ISRs), Global side-effects, Benefits, Pain, Visual Analog Scale (VAS), and Rating of Pain. ISR subscale was defined as sum of scores for questions 17 to 20, with a minimum possible total score of 4 and a maximum possible total score of 20. Global side-effects subscale was defined as sum of scores for questions 21 to 23 with minimum possible total score of 3 and a maximum possible total score of 15. Benefits (question 35); description of pain (question 36); VAS (question 37); rating of pain (question 38) subscales ranged from minimum possible score of 1 and a maximum possible total score of 5. For each of the subscales, lower scores indicated better satisfaction. Difference between both the groups at Week 4, 8 and 12 for individual sub-scales is presented in statistical analysis section.

HADS was used to measure depression and anxiety in subjects. The scale was limited to 14 questions. Seven of the items related to anxiety and 7 related to depression. Each item on the questionnaire was scored from 0-3 giving a total score between 0 and 21 for either anxiety or depression where higher score indicates more anxiety/depression.

FSS is a method designed to assess disabling fatigue in all the individuals. The Fatigue Severity Scale is a 9-item questionnaire developed to assess the level of fatigue due to neurological disease, were each item assessed on a 1-7 scale (1= no fatigue and 7= severe fatigue). The total score was calculated as the average of individual 9-items and ranged from 1 to 7 with a higher value indicating greater impairment due to fatigue.

PSQI is a self-rated questionnaire which assess sleep quality and disturbances over a 1-month interval using seven clinically derived components of sleep difficulties: sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction. PSQI is a summary of 7 components. Each component is scored from 0 to 3, therefore PSQI has a range of 0 (better) to 21 (worse). Interpretation of the PSQI is that a score less than 5 is associated with good sleep quality and a score of 5 or greater is associated with poor sleep quality.

The MusiQoL is a validated 31-item questionnaire describing 9 dimensions: activities of daily living (8 items); psychological well-being (4 items); symptoms (3 items); relationships with friends (4 items); relationships with family (3 items); relationship with healthcare system (3 items); sentimental and sexual life (2 items); coping (2 items); and rejection (2 items). Each of the questions was answered using a 6-point Likert scale ranging from 1 (never/not at all) to 6 (always/very much). The scores of each dimension were obtained by computing mean of the item scores of dimension with negatively worded item scores reversed so that higher scores indicated higher health-related quality of life (QoL). All 9 dimension scores were linearly transformed to a 0 to 100 scale and the average of the 9 dimensions was used to give a Global Score ranging from 0 to 100, where higher scores indicated higher health-related quality of life (QoL).

Adherence to treatment was calculated as 100 x the number of completed injections the subject administered divided by the expected number of injections. Treatment adherence was divided in two categories: percentage of subjects with less than (<) 80 percent adherence and percentage of subjects with more than or equal to (>=) 80 percent adherence.

Results are presented for three cytokines: leptin, resistin and adiponectin.

Correlation was assessed by using Pearson correlation coefficient. The MSTCQ was used as a tool to measure treatment satisfaction, focusing on the attributes specific to MS medications. The FLS subscale of MSTCQ was defined as the sum of the scores for questions 13 to 16 with a minimum possible total FLS score = 1 and a maximum possible total FLS score = 20. Lower score indicates lower flu like symptoms and better satisfaction.

Correlation was assessed by using Pearson correlation coefficient. MSTCQ, HADS, FSS, PSQI and MusiQOL are described in the above endpoints. Following abbreviations used in the categories: Global side-effects (GLOBSE); description of pain (PAINDESCR).

Results are presented for cytokines: leptin and resistin.

Polysomnography (PSG) was performed for subjects who participated in the sub study. PSG is a multi-parametric test used in the study of sleep and as a diagnostic tool in sleep medicine. Total sleep time is the total of all REM and non-REM sleep in a sleep episode.

Correlations between change from baseline at Week 12 in TST or REM sleep and the area under the curve (AUC) calculated using the trapezoidal method for cytokine levels (i.e., leptin, resistin, adiponectin, Interleukin (IL)-12, IL 10, and IL 6) were analyzed using Pearson's correlation coefficient. Polysomnography (PSG) was performed for subjects who participated in the sub study.

An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug.