To determine the individual disease activity scores and their evolution since baseline (improvement/worsening), the 9-Hole Peg Test (9-HPT) is performed. The 9-HPT evaluates manual dexterity by measuring the time it takes for the participant to move nine pegs from a box into nine holes on a board and back. Lower times indicate better dexterity and hand function, while higher times suggest greater impairment. The test will be carried out twice per hand, starting with the dominant hand, and the best performance will be used.

To determine the individual disease activity scores and their evolution since baseline (improvement/worsening), the Timed 25-Foot Walk (T25FW) is performed. The T25FW measures the time it takes for the patient to walk a distance of 25 ft (7,62 m) in their usual manner. Shorter times indicate better walking ability and mobility, while longer times suggest greater impairment.

To determine the individual disease activity scores and their evolution since baseline (improvement/worsening), the Stroop Test (Victoria Version) is performed. The Stroop Test measures processing speed and inhibition ability. First round: Participant is presented with 24 coloured dots and is asked to name the colour of the dots as fast as possible. Second round: Participant sees coloured random words (when, and, hard, over) and is asked to name the colour of each word as fast as possible. Third round: Participants is presented with 24 coloured words spelling colours (and the printed colour of the word is not the same as spelled colour), and is asked to name the printed colour as fast as possible. The test gives three scores based on the number of completed items in each round, and interference scores can be calculated.

To determine the individual disease activity scores and their evolution since baseline (improvement/worsening), the Symbol Digit Modalities Test (SDMT) is performed. The SDMT measures information processing speed. The participant is presented with a key, matching symbols to numbers (1-9). The participant must then use this key to orally (or in written form) match symbols to digits from list during 90 seconds and the number of correctly matched symbols are counted. Higher scores indicate better cognitive processing speed and efficiency, while lower scores suggest slower processing speed and potential cognitive impairment.

To determine the individual disease activity scores and their evolution since baseline (improvement/worsening), the Trail Making Test A&B (TMT A&B) is performed. The TMT A&B evaluates information processing speed and mental flexibility. In part A, the participants are asked to connect numbers in ascending order (randomly spread out on a sheet) with a pencil as fast as they can. In part B there is an additional sequence (alphabet), also randomly spread out on the sheet. The participants must now connect switching from number to letter (e.g., 1-A-2-B-3-C…) as fast as they can. In each part, the result is measured as time to completion of the task. Lower completion times indicate better cognitive functioning, while higher times may suggest difficulties with cognitive flexibility and processing speed.

To determine the individual disease activity scores and their evolution since baseline (improvement/worsening), the Multiple Sclerosis Inventory of Cognition (MUSIC) is performed. The MUSIC evaluates various cognitive domains such as memory, attention, processing speed, and executive function. The number of correctly associated words within 1 min is measured, not counting in repetitions or missed alternations. Higher scores indicate better cognitive performance, while lower scores suggest cognitive impairment.

To determine the individual disease activity scores and their evolution since baseline (improvement/worsening), the Digit span backwards (DSB) is performed. The DSB assesses working memory. The tester reads out a series of random digits, which the participants must repeat starting from the last digit going to the first e.g.: tester: "1, 2, 3", participant: "3, 2, 1". The test starts with 3 digits, after each successful round (2 series of digits) the series increases 1 digit. The test goes on until the participant fails twice to reproduce the series backwards.

To determine the individual disease activity scores and their evolution since baseline (improvement/worsening), the Rey-Osterrieth Complex Figure Test (ROCF) is performed. The ROCF tests visuo-constructive abilities, visual memory and executive functioning (mainly planning). Participants are asked to copy and memorise a complex figure, then draw from memory after ~ 3 minutes and draw once more after ~ 30 minutes. The test proposed by Taylor (1959), which is an adapted version of the original, is used. Scoring is determined by the number of correctly drawn sub-sections of the complex figure and their position. The maximum score is 36 (18 subsections with 2 possible points per subsection (1 for correctly drawn, 1 for correctly placed). Higher scores indicate better visuospatial and memory performance, while lower scores suggest impairments in these cognitive functions.

To determine the individual disease activity scores and their evolution since baseline (improvement/worsening), the Verbal Learn und Memory Test (VLMT) is performed. The VLMT assesses verbal learning and memory by having participants memorize and recall 15 words read aloud by a rater. This process is repeated five times with new word lists introduced between trials. The participant recalls the initial list immediately and again after a 20-30 minute delay. Scores range from 0 to 75 for learning trials and 0 to 15 for immediate and delayed recall, where higher scores indicate better memory performance and lower scores indicate cognitive challenges. The VLMT is the German precursor to the California auditory-verbal learning test.

To determine the individual disease activity scores and their evolution since baseline (improvement/worsening), the Near vision acuity test is performed. The Near Vision Acuity Test measures how well a person can see and read at close distances, using a common near vision chart according to manufacturer instructions. Common charts yield ratio values from 0.1 to 1.2. The test is non-verbal. Higher scores indicate better near vision acuity, while lower scores suggest difficulties with seeing close-up details.

To determine the individual disease activity scores and their evolution since baseline (improvement/worsening), the Contrast vision test (Pelli-Robson low-contrast chart) is performed. This is a contrast discrimination test to detect visual disturbances (with equally large letters of decreasing contrast, organized in triplets, to be read at a distance of 1 m). The participant is asked to name the letters and the test continues until two or more errors are made for a triplet of letters. Contrast sensitivity is determined by the last triplet in which the participant can correctly name two of three letters, and the chart's log sensitivity range is from 0 to 2.25.

The Short-form Food Frequency Questionnaire is used to ask five questions about the typical weekly diet.

To assess the quality of life and disease activity and their evolution since baseline (improvement/worsening), the Fatigue Severity Scale (FSS) is distributed through the Healios+Me app. The FSS is a self-report questionnaire that measures the severity of fatigue and how it has interfered with certain activities during the past 14 days. Scores range from 1 to 7 for each statement, with higher scores indicating greater severity of fatigue symptoms. Lower scores suggest milder fatigue symptoms or less impact on daily life.

To assess the quality of life and disease activity and their evolution since baseline (improvement/worsening), the Multiple Sclerosis Impact Scale (MSIS-29) is distributed through the Healios+Me app. The MSIS-29 is a self-report questionnaire that measures the physical and psychological impact of MS during the past 2 weeks. Scores range from 0 to 100 for each subscale, with higher scores indicating a greater impact of MS on physical and psychological well-being. Lower scores suggest less impact and better quality of life in these domains.

To assess the quality of life and disease activity and their evolution since baseline (improvement/worsening), the MS Symptom Tracker is integrated in the Healios+Me app. The MS Symptom Tracker consists of questions regarding symptoms experienced during the past 2 weeks.

To assess the quality of life and disease activity and their evolution since baseline (improvement/worsening), Relapse reporting is integrated through the Healios+Me app. It allows patients to report in the app when a relapse has occurred, following a structured questionnaire.

To assess the quality of life and disease activity and their evolution since baseline (improvement/worsening), the Multiple Sclerosis Quality of Life-54 (MSQoL-54) is performed. The MSQoL-54 is a self-report questionnaire on quality of life with 36 generic and 18 MS-specific items. Scores are calculated for each domain and range from 0 to 100, with higher scores indicating better quality of life. Lower scores indicate poorer quality of life in the respective domains assessed by the questionnaire.

To assess the quality of life and disease activity and their evolution since baseline (improvement/worsening), the Hospital Anxiety and Depression Scale (HADS) is performed. The HADS is a self-report questionnaire on anxiety and depression symptoms with 14 items. Each item is scored on a scale from 0 to 3, with higher scores indicating higher levels of anxiety or depression. Total scores for each subscale (anxiety and depression) range from 0 to 21, where higher scores indicate more severe symptoms of anxiety or depression.

To assess the quality of life and disease activity and their evolution since baseline (improvement/worsening), the PROMIS Self-Efficacy for Managing Chronic Conditions - Managing Symptoms - Short Form 8a is used. It consists of 8 items that ask respondents to rate their level of confidence in managing various symptoms on a scale from 1 (not at all confident) to 5 (totally confident). Higher scores indicate greater self-efficacy in managing symptoms associated with chronic conditions.

To assess the quality of life and disease activity and their evolution since baseline (improvement/worsening), the PROMIS Numeric Rating Scale v1.0 - Pain Intensity 1a is used. It consists of a single item where respondents rate their pain intensity on a numeric scale from 0 (no pain) to 10 (worst imaginable pain). Higher scores indicate higher levels of pain intensity reported by the individual.

To assess the quality of life and disease activity and their evolution since baseline (improvement/worsening), the PROMIS Short Form v1.1 - Pain Interference 4a is used. It consists of four items that ask about the impact of pain on activities, mood, relationships, and enjoyment of life. Responses are scored on a 5-point scale ranging from 1 (not at all) to 5 (very much). Higher scores indicate greater pain interference, reflecting more significant impacts of pain on daily activities and quality of life.

To assess the quality of life and disease activity and their evolution since baseline (improvement/worsening), the PROMIS Short Form v2.0 - Cognitive Function - Abilities 8a is used. It consists of eight items that ask about various cognitive functions such as memory, concentration, and problem-solving abilities. Responses are scored on a 5-point scale ranging from 1 (not at all) to 5 (very much). Higher scores indicate better perceived cognitive abilities, reflecting higher levels of cognitive function and capability in daily activities.

To assess the quality of life and disease activity and their evolution since baseline (improvement/worsening), the PROMIS Scale v1.2 - Global Health is used. It includes 10 items covering physical, mental, and social health domains. Responses are rated on a 5-point scale ranging from 1 (poor) to 5 (excellent). Higher scores indicate better perceived global health, encompassing physical, mental, and social aspects of well-being.

To assess the quality of life and disease activity and their evolution since baseline (improvement/worsening), the electronic Health (eHealth) Literacy Scale (eHEALS) is evaluated. The eHEALS is a self-report questionnaire with 8 items measuring patients' knowledge, comfort, and perceived ability to find, evaluate, and apply electronic health information to one's health problems. It consists of 8 items rated on a 5-point Likert scale from 1 (strongly disagree) to 5 (strongly agree). Higher scores indicate higher levels of perceived eHealth literacy, reflecting greater confidence and ability in using online health information effectively.