A Phase 4 Study to Assess the Impact of Patient Support Program on Health Related Quality of Life and Adherence in Subjects With Relapsing-Remitting Multiple Sclerosis Administered Rebif® With the RebiSmart™ Device

Multiple Sclerosis Impact Scale-29 (MSIS-29) is a validated MS specific questionnaire consisting of 29 questions of which 20 addressed the physical impact component and 9 assessed the psychological impact. A combined score can be generated, or both components can be reported separately. The psychological wellbeing assessment portion of the MSIS-29 was comprised of 9 questions in which subjects rate the impact of MS on their day-to-day life from 1=no impact to 5=extreme impact. The total Psychological Score was calculated using following formula: sum of score for 9 questions - 9/0.36. The total score range ranges from 0-100 where, lower total score indicates less psychologically-related impact while a higher total score indicates greater psychologically-related impact on a subject's functioning.

Time frame: Baseline and Month 12

Population: The ITT population included all subjects randomized into the trial and have completed at least 1 post-baseline assessment of the questionnaires.

Quality of life was assessed using the EQ5D-5L score, which is one of the most widely used generic index measures of health-related quality of life. It consists of a 5-item descriptive system that measures 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension comprises 5 levels with corresponding numeric scores ranging from 1 (no problems) through 5 (extreme problems) in which 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. A unique EQ5D-5L health state was defined by combining the numeric level scores for each of the 5 dimensions and the total score ranges from 5 to 25. An increase in the EQ5D-5L total score indicates worsening.

Time frame: Baseline, Month 6 and 12

Population: ITT population included all subjects randomized into the trial and have completed at least 1 post-baseline assessment of the questionnaires.

EQ-5D-5L VAS was used to record a subject's rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 = worst imaginable health state and 100 = best imaginable health state.

Time frame: Baseline, Month 6 and 12

Population: ITT population included all subjects randomized into the trial and have completed at least 1 post-baseline assessment of the questionnaires.

Fatigue Severity Scale (FSS) is a method of evaluating fatigue in multiple sclerosis and is designed to differentiate fatigue from clinical depression, since both share some of the same symptoms. The Fatigue Severity Scale is a 9-item questionnaire developed to assess the level of fatigue due to neurological disease, were each 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.

Time frame: Baseline, Month 6 and 12

Population: ITT population included all subjects randomized into the trial and have completed at least 1 post-baseline assessment of the questionnaires.

Hospital Anxiety and Depression Scale (HADS) was used to measure depression and anxiety in patients. The scale was limited to 14 questions, a practical tool for identifying and quantifying the two most common forms psychological disturbances in medical subjects. 7 of the items relate to anxiety and 7 relate 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.

Time frame: Baseline, Month 6 and 12

Population: ITT population included all subjects randomized into the trial and have completed at least 1 post-baseline assessment of the questionnaires.

The Modified Fatigue Impact Index assesses fatigue- severity, distress, or degree of interference. Modified Fatigue Impact Scale Index was expressed in terms of percentage and ranged from 0% (no fatigue) to 100% (almost always impacted by fatigue).

Time frame: Baseline, Month 6 and 12

Population: ITT population included all subjects randomized into the trial and have completed at least 1 post-baseline assessment of the questionnaires. Here, Number of subjects analyzed signifies those subjects who were evaluable for this outcome Measure.

The Modified Fatigue Impact Scale is a list of 21 statements describing how fatigue may affect a person's functioning. Answers ranging from 0 (Never) to 4 (Almost always). A total score ranged from a possible 0 (no fatigue impact) to 84 (almost always impacted by fatigue). A lower total score indicates less fatigue-related impact while a higher total score indicates greater fatigue-related impact on a subject's functioning.

Time frame: Baseline, Month 6 and 12

Population: ITT population included all subjects randomized into the trial and have completed at least 1 post-baseline assessment of the questionnaires.. Here, Overall Number of subjects analyzed signifies those subjects who were evaluable for this outcome Measure.

Multiple Sclerosis Impact Scale-29 (MSIS-29) is a validated MS specific questionnaire consisting of 29 questions of which 20 addressed the physical impact component and 9 assessed the psychological impact. A combined score can be generated, or both components can be reported separately. The psychological wellbeing assessment portion of the MSIS-29 was comprised of 9 questions in which subjects rate the impact of MS on their day-to-day life from 1=no impact to 5=extreme impact. The total Psychological Score was calculated using following formula: sum of score for 9 questions - 9/0.36. The total score range ranges from 0-100 where, lower total score indicates less psychologically-related impact while a higher total score indicates greater psychologically-related impact on a subject's functioning.

Time frame: Baseline and Month 6

Population: ITT population included all subjects randomized into the trial and have completed at least 1 post-baseline assessment of the questionnaires.

Multiple Sclerosis Impact Scale-29 (MSIS-29) is a validated MS specific questionnaire consisting of 29 questions of which 20 addressed the physical impact component and 9 assessed the psychological impact. A combined score can be generated, or both components can be reported separately. The total score of the MSIS-29 was comprised of all the 29 questions in which subjects rate the impact of MS on their day-to-day life from 1=no impact to 5=extreme impact. The total Score was calculated using following formula: sum of score for 29 questions - 29/1.45. The total score range ranges from 0-100 where, lower total score indicates less psychologically-related impact while a higher total score indicates greater psychologically-related impact on a subject's functioning.

Time frame: Baseline, Month 6 and 12

Population: ITT population included all subjects randomized into the trial and have completed at least 1 post-baseline assessment of the questionnaires.

Subjects defined up to 4 personal lifestyle goals during the first study week. Subjects completed the following questions related to lifestyle goals achieved during this study: 1. Was the goal achieved? (Yes/No) 2. If yes, better than expected or achieved as expected? 3. If better than expected, a lot or a little better than expected? 4. If no, a little or a lot less than expected?

Time frame: Month 12

Population: ITT population included all subjects randomized into the trial and have completed at least 1 post-baseline assessment of the questionnaires. Here, n signifies subjects who were evaluable for the specific goal in this outcome measure.

The subject satisfaction questionnaire was defined as satisfaction with overall treatment and support from health care providers during the last 12 months. Subjects were asked to rate their satisfaction by choosing either Very unsatisfied, unsatisfied, satisfied or very satisfied.

Time frame: Month 12

Population: ITT population included all subjects randomized into the trial and have completed at least 1 post-baseline assessment of the questionnaires. Here, Overall Number of Participants Analyzed signifies those subjects who were evaluable for this outcome measure.

Lifestyle Questionnaire was used to assess the quality of life for subjects based on following parameters: Stress, Alcohol, Cost, Physical Aspect, Sleep, Activity and Smoking. Subjects provided their responses on the basis of three color codes: Green, Orange and Red, where Green refers to - no problem; Orange refers to - some problem and red refers to - definite/debilitating problem.

Time frame: Month 6 and 12

Population: ITT population was used. Here, Overall Number of Participants Analyzed signifies those subjects who were evaluable for this outcome Measure and n signifies those subjects who were evaluable for specified time points, respectively.

The subject satisfaction questionnaire was defined as satisfaction with overall treatment and support from health care providers during the last 12 months. Subjects were asked to rate their satisfaction by choosing either Very discontented, discontented, contented or Very contented.

Time frame: Month 12

Population: ITT population included all subjects randomized into the trial and have completed at least 1 post-baseline assessment of the questionnaires. Here, Number of Subjects Analyzed signifies those subjects who were evaluable for this outcome measure.

Working ability was assessed by measuring the number of subjects for the following categories: 1) Subjects with full sickness/disability pension, 2) Subjects who were employed or had their own business, 3) Subjects who were retired, 4) Subjects who were studying, 5) None of the above.

Time frame: Month 12

Population: ITT population included all subjects randomized into the trial and have completed at least 1 post-baseline assessment of the questionnaires. Here, Overall Number of subjects analyzed signifies those subjects who were evaluable for this outcome Measure.

AE was defined as any untoward medical occurrence which does not necessarily have a causal relationship with this the study drug. An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE 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. Treatment Emergent Adverse Events (TEAEs) include both Serious TEAEs and non-serious TEAEs.

Time frame: Baseline up to Month 12

Population: The Safety Population included all subjects who were randomized and received at least 1 dose of trial treatment.

According to the World Health Organisation (WHO), treatment adherence is defined as both compliance (taking the medication in the correct dose and according to the schedule prescribed) and persistency (maintenance of the drug regimen over the long-term). Percentage of subjects with \<10% missed injections (measured with the software RDS 2.0) during 6 and 12 months were reported.

Time frame: Month 6 and 12

Population: ITT population included all subjects randomized into the trial and have completed at least 1 post-baseline assessment of the questionnaires.