A Study of Suboptimally Controlled Participants Previously Taking Oral or Infusion DMDs for RMS (MASTER-2)

A relapse was defined as per routine clinical practice as determined by the investigator. As a guide, relapse may be defined as exacerbation of symptoms that occur over a minimum of 24 hours and separated from a previous attack by at least 30 days, in the absence of fever or infection. ARR was calculated as the total number of reported relapses in the 24 months after treatment divided by the days on study corresponding to relapse information and multiplied by 365.25.

The TSQM-14 was a participant-rated scale used to assess subjective satisfaction with medication. The TSQM has 14 questions that assesses participants' global satisfaction level with their treatment in 4 domains: side effects (There are 5 questions in the side effects domain, however one of them is a Yes/No question and there are 4 sub-components, hence a maximum score of 20), effectiveness (3 questions), global satisfaction (3 questions), and convenience (3 questions). All questions are scored from 1 (least satisfied) to 5 or 7 (most satisfied). The total score is summed for each domain to obtain: side effects (1-20), effectiveness (1-21), global satisfaction (1-17), and convenience (1-21), using transformed scores between 0 and 100. Lower total scores in each domain indicate dissatisfaction with the study medication and higher total scores indicate satisfaction.

The SF-36 Health Survey is a validated, self-administered questionnaire designed to assess general health status across eight domains: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. It includes one item evaluating perceived change in health over the past year and generates two summary scores-the Physical Component Summary (PCS) and Mental Component Summary (MCS)-derived using factor analytic methods. Each domain and summary score is scaled from 0 to 100, with higher scores indicating better health status.

The MFIS-5 is a shortened version of the Fatigue Impact Scale consisting of 5 items that assess the impact of fatigue on physical, cognitive, and psychosocial functioning. Each item is rated on a 5-point Likert scale: 0 (Never), 1 (Rarely), 2 (Sometimes), 3 (Often), and 4 (Almost always). The total score ranges from 0 to 20, with higher scores indicating a greater impact of fatigue. Items include: reduced alertness, limitations in activities away from home, difficulty sustaining physical effort, reduced ability to complete tasks requiring physical effort, and trouble concentrating.

The 7-item Beck Depression Inventory-Fast Screen (BDI-FS) is a self-report tool used to assess the severity of depressive symptoms. It includes seven items: Sadness, Pessimism, Past Failure, Loss of Pleasure, Self-Dislike, Self-Criticalness, and Suicidal Thoughts. Each item is rated on a 4-point scale from 0 to 3, with higher scores indicating greater symptom severity. The total score ranges from 0 to 21 and is calculated by summing the highest-rated response for each item.

The WPAI-MS questionnaire is a 6-item validated instrument to measure impairments in work and activities. The WPAI-MS included 6 questions: 1 (if currently employed); 2 (hours missed due to disease); 3 (hours missed other reasons); 4 (hours actually worked); 5 (degree disease affected productivity while working); 6 (degree disease affected regular activities). WPAI-MS generated four component scores: percentage of work time missed (absenteeism); percentage of impairment while working (presentisms); percentage of overall work impairment (absenteeism and presentisms combined); and percentage of activity impairment. Scores for WPAI range from 0% to 100%, where 0 % indicates no impairment and 100% is total loss of work productivity/activity. Change from baseline in percentage of work time missed (absenteeism) was reported.

The WPAI-MS questionnaire is a 6-item validated instrument to measure impairments in work and activities. The WPAI-MS included 6 questions: 1 (if currently employed); 2 (hours missed due to disease); 3 (hours missed other reasons); 4 (hours actually worked); 5 (degree disease affected productivity while working); 6 (degree disease affected regular activities). WPAI-MS generated four component scores: percentage of work time missed (absenteeism); percentage of impairment while working (presentisms); percentage of overall work impairment (absenteeism and presentisms combined); and percentage of activity impairment. Scores for WPAI range from 0% to 100%, where 0 % indicates no impairment and 100% is total loss of work productivity/activity. Change from baseline in percentage of impairment while working (presentisms) was reported.

The WPAI-MS questionnaire is a 6-item validated instrument to measure impairments in work and activities. The WPAI-MS included 6 questions: 1 (if currently employed); 2 (hours missed due to disease); 3 (hours missed other reasons); 4 (hours actually worked); 5 (degree disease affected productivity while working); 6 (degree disease affected regular activities). WPAI-MS generated four component scores: percentage of work time missed (absenteeism); percentage of impairment while working (presentisms); percentage of overall work impairment (absenteeism and presentisms combined); and percentage of activity impairment. Scores for WPAI range from 0% to 100%, where 0 % indicates no impairment and 100% is total loss of work productivity/activity. Change from baseline in total percentage of work impairment (absenteeism and presentisms) were reported.

The WPAI-MS questionnaire is a 6-item validated instrument to measure impairments in work and activities. The WPAI-MS included 6 questions: 1 (if currently employed); 2 (hours missed due to disease); 3 (hours missed other reasons); 4 (hours actually worked); 5 (degree disease affected productivity while working); 6 (degree disease affected regular activities). WPAI-MS generated four component scores: percentage of work time missed (absenteeism); percentage of impairment while working (presentisms); percentage of overall work impairment (absenteeism and presentisms combined); and percentage of activity impairment. Scores for WPAI range from 0% to 100%, where 0 % indicates no impairment and 100% is total loss of work productivity/activity. Change from baseline in percentage of activity impairment was reported.

The PDDS is a patient-reported scale to assess the disability status in participants with MS, and it focuses mainly on how participants walk. Scores on the PDDS range from 0 (normal) to 8 (bedridden): 0 (Normal), 1 (Mild Disability), 2 (Moderate Disability), 3 (Gait Disability), 4 (Early Cane), 5 (Late Cane), 6 (Bilateral Support), 7 (Wheelchair/Scooter), and 8 (Bedridden). A higher score represents higher level of disability.

7 Treatment adherence questions, based on MS-TAQ, were developed to determine level of adherence as well as identify barriers to adherence for MS participants taking DMDs. 1.What treatment week of cladribine (Clad.) tablets (tab.) did you most recently complete? 2.How many Clad. tab. were you supposed to take during this treatment week? 3.Did you miss/forget to take any Clad. tab. during this treatment week? 4. How many Clad. tab. did you miss/ forget to take? 5.How important were following factors in missing/forgetting to take a dose? (scale from 0-3, where, 0=Not important at all and 3=Extremely important). 6.Overall, how hard/easy do you feel it is to take Clad. tab. as recommended by your physician during your treatment week? (scale from 1- 5, where 1=Extremely easy and 5=Extremely hard). 7.How satisfied are you with how things have been with your Clad. tab. treatment during your treatment week? (scale from 1-5, where 1=Not satisfied at all and 5=Completely satisfied).

A relapse was defined as per routine clinical practice as determined by the investigator. As a guide, relapse may be defined as exacerbation of symptoms that occur over a minimum of 24 hours and separated from a previous attack by at least 30 days, in the absence of fever or infection.

A relapse was defined according to routine clinical practice as determined by the investigator. A relapse will be associated with hospitalization if the participants will be hospitalized for the relapse. As a guide, relapse was considered an exacerbation of symptoms that occurred over a minimum of 24 hours and was separated from a previous attack by at least 30 days, in the absence of fever or infection. The percentage of participants who experienced a relapse associated with hospitalization was reported.

The qualifying relapse is the occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis (MS) (for more than [>] 24 hours, no fever, infection, injury, adverse events (AEs), and preceded by a stable or improving neurological state for more than or equal to [>=] 30 days).ARR was calculated as the total number of reported relapses in the 24 months after treatment divided by the days on study corresponding to relapse information and multiplied by 365.25. ARR associated with hospitalization at Months 12 and 24 were reported. A relapse was associated with hospitalization if the participant will be hospitalized for the relapse.

A relapse was defined according to routine clinical practice as determined by the investigator. As a guide, relapse was considered an exacerbation of symptoms that occurred over a minimum of 24 hours and was separated from a previous attack by at least 30 days, in the absence of fever or infection. The percentage of participants with relapse associated with glucocorticoid use over the 12-month period, 13th to 24th month and over the 24-month period of treatment with cladribine tablets was reported.

The qualifying relapse is the occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis (MS) (for more than [>] 24 hours, no fever, infection, injury, adverse events (AEs), and preceded by a stable or improving neurological state for more than or equal to [>=] 30 days). ARR was calculated as the total number of reported relapses in the 24 months after treatment divided by the days on study corresponding to relapse information and multiplied by 365.25. ARR associated with glucocorticoid use at Months 12 and 24 were reported. A relapse will be associated with glucocorticoid use if steroid treatment will be required for the relapse.

Number of previous DMD received by participants with MS were reported.

Percentage of participants who discontinued cladribine tablets were reported.

Number of participants who discontinued cladribine tablets in each category of reason for discontinuation were reported.

Elapsed time to discontinuation after first dose of cladribine tablets was reported. Elapsed time to discontinuation of cladribine tablets is calculated by subtracting the date of the first study dose from the date on which the participant discontinued cladribine tablets.

Number of doses received by participants as per United States prescribing information were reported.

Total planned doses received by participants as per United States Prescribing Information was reported.

Percentage of participants with subsequent treatment chosen following discontinuation of cladribine tablets was reported. The percentages were calculated using the number of participants who discontinued Cladribine tablets as denominator.

Number of participants with at least one concomitant medication were reported.

A relapse was defined as an exacerbation of symptoms that occurred over a minimum of 24 hours and was separated from a previous attack by at least 30 days, in the absence of fever or infection. Annualized relapse rate (ARR) during the 24 months prior to baseline, based on retrospectively collected data, was reported. ARR was calculated as the total number of reported relapses in the 24 months after treatment divided by the days on study corresponding to relapse information and multiplied by 365.25.

A serious adverse event (SAE) is an adverse event (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 is otherwise considered medically important. An ADR is a response to a medicinal product which is noxious and unintended. An AESI is an AE of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the Sponsor can be appropriate. Special Situations included AEs related to pregnancy, overdose, off-label use, misuse, medication error, occupational exposure, or lack of therapeutic effectiveness.