Trial Outcomes & Findings for Discontinuation of Disease Modifying Therapies (DMTs) in Multiple Sclerosis (MS) (NCT NCT03073603)

NCT ID: NCT03073603

Last Updated: 2023-08-16

Results Overview

The outcome is the proportion of participants in each group developing a new MS relapse and/or MRI brain lesion over the course of the study duration. Count of Participants with either a new MS relapse and/or a new brain MRI lesion is reported.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 259 participants
• Primary outcome timeframe: 18-24 months, based on time of enrollment
• Results posted on: 2023-08-16

Participant Flow

Participant milestones

Measure	Drug Continuation Arm Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Standard of Care: Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.	Drug Discontinuation Arm Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Discontinuation of disease modifying therapy: Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Overall Study STARTED	128	131
Overall Study COMPLETED	106	123
Overall Study NOT COMPLETED	22	8

Reasons for withdrawal

Measure	Drug Continuation Arm Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Standard of Care: Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.	Drug Discontinuation Arm Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Discontinuation of disease modifying therapy: Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Overall Study Noncompliance	3	1
Overall Study Adverse Event	5	3
Overall Study Physician Decision	1	2
Overall Study Required treatment not allowed by protocol	1	0
Overall Study Financial or insurance-related	8	0
Overall Study Withdrawal by Subject	0	1
Overall Study Discontinued DMT	4	0
Overall Study Restarted DMT	0	1

Baseline Characteristics

Discontinuation of Disease Modifying Therapies (DMTs) in Multiple Sclerosis (MS)

Baseline characteristics by cohort

Measure	Drug Continuation Arm n=128 Participants Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Standard of Care: Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.	Drug Discontinuation Arm n=131 Participants Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Discontinuation of disease modifying therapy: Participants who will discontinue their current MS drug. No other changes to their treatment occur.	Total n=259 Participants Total of all reporting groups
Age, Continuous	63.0 years STANDARD_DEVIATION 5.2 • n=5 Participants	63.1 years STANDARD_DEVIATION 4.9 • n=7 Participants	63.0 years STANDARD_DEVIATION 5.0 • n=5 Participants
Sex: Female, Male Female	107 Participants n=5 Participants	109 Participants n=7 Participants	216 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	22 Participants n=7 Participants	43 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	12 Participants n=5 Participants	11 Participants n=7 Participants	23 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White	112 Participants n=5 Participants	119 Participants n=7 Participants	231 Participants n=5 Participants
Race/Ethnicity, Customized Other	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment United States	128 Participants n=5 Participants	131 Participants n=7 Participants	259 Participants n=5 Participants
MS Phenotype Primary Progressive	2 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants
MS Phenotype Secondary Progressive	18 Participants n=5 Participants	17 Participants n=7 Participants	35 Participants n=5 Participants
MS Phenotype Relapsing-Remitting	108 Participants n=5 Participants	108 Participants n=7 Participants	216 Participants n=5 Participants
Time since first onset of symptoms related to MS	20.9 years STANDARD_DEVIATION 10.4 • n=5 Participants	23.4 years STANDARD_DEVIATION 10.5 • n=7 Participants	22.2 years STANDARD_DEVIATION 10.5 • n=5 Participants
Time since last documented relapse	13.2 years STANDARD_DEVIATION 6.2 • n=5 Participants	14.5 years STANDARD_DEVIATION 7.4 • n=7 Participants	13.9 years STANDARD_DEVIATION 6.9 • n=5 Participants

PRIMARY outcome

Timeframe: 18-24 months, based on time of enrollment

The outcome is the proportion of participants in each group developing a new MS relapse and/or MRI brain lesion over the course of the study duration. Count of Participants with either a new MS relapse and/or a new brain MRI lesion is reported.

Outcome measures

Measure	Drug Continuation Arm n=128 Participants Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Standard of Care: Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.	Drug Discontinuation Arm n=131 Participants Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Discontinuation of disease modifying therapy: Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Number of Participants Developing a New MS Relapse and/or MRI Brain Lesion Over the Course of the Study Duration	6 Participants	16 Participants

SECONDARY outcome

Timeframe: Baseline, then every 6 months for up to a maximum of 24 months, based on time of enrollment.

Population: Three subjects (2 in drug continuation arm and 1 in drug discontinuation arm) did not have a baseline EDSS recorded, so change in EDSS could not be assessed.

The EDSS is a neurological examination performed by a blinded rater. This assessment is collected at each study visit. Increase in the EDSS score shows disease activity or progression, and must be observed six months later to be confirmed. Whether a confirmed change is significant depends on the subject's EDSS at baseline: for those with a baseline EDSS of 5.5 points or fewer, the increase must be at least one point to be significant; for those with a baseline EDSS of 6.0 points or greater, a change of at least 0.5 points is considered significant. We will calculate the percentage in each group of those who had a significant change at anytime during the follow-up period, which was then confirmed at 6 months later.

Outcome measures

Measure	Drug Continuation Arm n=126 Participants Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Standard of Care: Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.	Drug Discontinuation Arm n=130 Participants Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Discontinuation of disease modifying therapy: Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Number With Disability Progression Confirmed at 6 Months Using the Expanded Disability Status Scale (EDSS)	14 Participants	16 Participants

SECONDARY outcome

Timeframe: Baseline, 18-24 Months, based on time of enrollment

Population: Subjects missing Neuro-QOL at either baseline or at Month 18-24 were excluded from this analysis

The Neuro-QOL Adult PRO short form measures are collected to evaluate self-reported overall quality of life and functioning in patients with a variety of neurological conditions including MS. The Neuro-Qol short form scales consist of 5-9 single scale item scales. Raw scores are then converted to a standardized score with mean 50 and standard deviation 10. The Neuro-QoL short forms used in this study with higher scores representing better outcomes are: Upper Extremity Function, Lower Extremity Function, Cognitive -- General Concerns, Cognitive -- Executive Function, Communication, Positive Affect and Well-Being, Satisfaction with Social Roles and Activities, and Ability to Participate in Social Roles and Activities. The short forms used with lower scores representing better outcomes are: Fatigue, Sleep Disturbance, Anxiety, Depression, and Emotional-Behavioral Dyscontrol.

Outcome measures

Measure	Drug Continuation Arm n=109 Participants Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Standard of Care: Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.	Drug Discontinuation Arm n=113 Participants Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Discontinuation of disease modifying therapy: Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Upper Extremity Function	-1.1 units on a scale Standard Deviation 6.2	-0.6 units on a scale Standard Deviation 5.8

SECONDARY outcome

Timeframe: Baseline, 18-24 Months, based on time of enrollment

Population: Subjects missing Neuro-QOL at either baseline or at Month 18-24 were excluded from this analysis

The Neuro-QOL Adult PRO short form measures are collected to evaluate self-reported overall quality of life and functioning in patients with a variety of neurological conditions including MS. The Neuro-Qol short form scales consist of 5-9 single scale item scales. Raw scores are then converted to a standardized score with mean 50 and standard deviation 10. The Neuro-QoL short forms used in this study with higher scores representing better outcomes are: Upper Extremity Function, Lower Extremity Function, Cognitive -- General Concerns, Cognitive -- Executive Function, Communication, Positive Affect and Well-Being, Satisfaction with Social Roles and Activities, and Ability to Participate in Social Roles and Activities. The short forms used with lower scores representing better outcomes are: Fatigue, Sleep Disturbance, Anxiety, Depression, and Emotional-Behavioral Dyscontrol.

Outcome measures

Measure	Drug Continuation Arm n=108 Participants Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Standard of Care: Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.	Drug Discontinuation Arm n=113 Participants Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Discontinuation of disease modifying therapy: Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Lower Extremity Function	-0.2 units on a scale Standard Deviation 5.5	-1.1 units on a scale Standard Deviation 5

SECONDARY outcome

Timeframe: Baseline, 18-24 Months, based on time of enrollment

Population: Subjects missing Neuro-QOL at either baseline or at Month 18-24 were excluded from this analysis

The Neuro-QOL Adult PRO short form measures are collected to evaluate self-reported overall quality of life and functioning in patients with a variety of neurological conditions including MS. The Neuro-Qol short form scales consist of 5-9 single scale item scales. Raw scores are then converted to a standardized score with mean 50 and standard deviation 10. The Neuro-QoL short forms used in this study with higher scores representing better outcomes are: Upper Extremity Function, Lower Extremity Function, Cognitive -- General Concerns, Cognitive -- Executive Function, Communication, Positive Affect and Well-Being, Satisfaction with Social Roles and Activities, and Ability to Participate in Social Roles and Activities. The short forms used with lower scores representing better outcomes are: Fatigue, Sleep Disturbance, Anxiety, Depression, and Emotional-Behavioral Dyscontrol.

Outcome measures

Measure	Drug Continuation Arm n=109 Participants Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Standard of Care: Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.	Drug Discontinuation Arm n=113 Participants Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Discontinuation of disease modifying therapy: Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Fatigue	-0.1 units on a scale Standard Deviation 6.2	-0.9 units on a scale Standard Deviation 6.8

SECONDARY outcome

Timeframe: Baseline, 18-24 Months, based on time of enrollment

Population: Subjects missing Neuro-QOL at either baseline or at Month 18-24 were excluded from this analysis

The Neuro-QOL Adult PRO short form measures are collected to evaluate self-reported overall quality of life and functioning in patients with a variety of neurological conditions including MS. The Neuro-Qol short form scales consist of 5-9 single scale item scales. Raw scores are then converted to a standardized score with mean 50 and standard deviation 10. The Neuro-QoL short forms used in this study with higher scores representing better outcomes are: Upper Extremity Function, Lower Extremity Function, Cognitive -- General Concerns, Cognitive -- Executive Function, Communication, Positive Affect and Well-Being, Satisfaction with Social Roles and Activities, and Ability to Participate in Social Roles and Activities. The short forms used with lower scores representing better outcomes are: Fatigue, Sleep Disturbance, Anxiety, Depression, and Emotional-Behavioral Dyscontrol.

Outcome measures

Measure	Drug Continuation Arm n=108 Participants Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Standard of Care: Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.	Drug Discontinuation Arm n=113 Participants Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Discontinuation of disease modifying therapy: Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Sleep Disturbance	-0.3 units on a scale Standard Deviation 5.6	-0.5 units on a scale Standard Deviation 5.7

SECONDARY outcome

Timeframe: Baseline, 18-24 Months, based on time of enrollment

Population: Subjects missing Neuro-QOL at either baseline or at Month 18-24 were excluded from this analysis

The Neuro-QOL Adult PRO short form measures are collected to evaluate self-reported overall quality of life and functioning in patients with a variety of neurological conditions including MS. The Neuro-Qol short form scales consist of 5-9 single scale item scales. Raw scores are then converted to a standardized score with mean 50 and standard deviation 10. The Neuro-QoL short forms used in this study with higher scores representing better outcomes are: Upper Extremity Function, Lower Extremity Function, Cognitive -- General Concerns, Cognitive -- Executive Function, Communication, Positive Affect and Well-Being, Satisfaction with Social Roles and Activities, and Ability to Participate in Social Roles and Activities. The short forms used with lower scores representing better outcomes are: Fatigue, Sleep Disturbance, Anxiety, Depression, and Emotional-Behavioral Dyscontrol.

Outcome measures

Measure	Drug Continuation Arm n=109 Participants Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Standard of Care: Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.	Drug Discontinuation Arm n=112 Participants Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Discontinuation of disease modifying therapy: Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- General Concerns	0.6 units on a scale Standard Deviation 5.6	1.5 units on a scale Standard Deviation 6.4

SECONDARY outcome

Timeframe: Baseline, 18-24 Months, based on time of enrollment

Population: Subjects missing Neuro-QOL at either baseline or at Month 18-24 were excluded from this analysis

The Neuro-QOL Adult PRO short form measures are collected to evaluate self-reported overall quality of life and functioning in patients with a variety of neurological conditions including MS. The Neuro-Qol short form scales consist of 5-9 single scale item scales. Raw scores are then converted to a standardized score with mean 50 and standard deviation 10. The Neuro-QoL short forms used in this study with higher scores representing better outcomes are: Upper Extremity Function, Lower Extremity Function, Cognitive -- General Concerns, Cognitive -- Executive Function, Communication, Positive Affect and Well-Being, Satisfaction with Social Roles and Activities, and Ability to Participate in Social Roles and Activities. The short forms used with lower scores representing better outcomes are: Fatigue, Sleep Disturbance, Anxiety, Depression, and Emotional-Behavioral Dyscontrol.

Outcome measures

Measure	Drug Continuation Arm n=105 Participants Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Standard of Care: Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.	Drug Discontinuation Arm n=112 Participants Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Discontinuation of disease modifying therapy: Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Executive Function	0.3 units on a scale Standard Deviation 6.3	0.3 units on a scale Standard Deviation 6.2

SECONDARY outcome

Timeframe: Baseline, 18-24 Months, based on time of enrollment

Population: Subjects missing Neuro-QOL at either baseline or at Month 18-24 were excluded from this analysis

The Neuro-QOL Adult PRO short form measures are collected to evaluate self-reported overall quality of life and functioning in patients with a variety of neurological conditions including MS. The Neuro-Qol short form scales consist of 5-9 single scale item scales. Raw scores are then converted to a standardized score with mean 50 and standard deviation 10. The Neuro-QoL short forms used in this study with higher scores representing better outcomes are: Upper Extremity Function, Lower Extremity Function, Cognitive -- General Concerns, Cognitive -- Executive Function, Communication, Positive Affect and Well-Being, Satisfaction with Social Roles and Activities, and Ability to Participate in Social Roles and Activities. The short forms used with lower scores representing better outcomes are: Fatigue, Sleep Disturbance, Anxiety, Depression, and Emotional-Behavioral Dyscontrol.

Outcome measures

Measure	Drug Continuation Arm n=105 Participants Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Standard of Care: Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.	Drug Discontinuation Arm n=109 Participants Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Discontinuation of disease modifying therapy: Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Communication	0.1 units on a scale Standard Deviation 2.2	-0.4 units on a scale Standard Deviation 3

SECONDARY outcome

Timeframe: Baseline, 18-24 Months, based on time of enrollment

Population: Subjects missing Neuro-QOL at either baseline or at Month 18-24 were excluded from this analysis

The Neuro-QOL Adult PRO short form measures are collected to evaluate self-reported overall quality of life and functioning in patients with a variety of neurological conditions including MS. The Neuro-Qol short form scales consist of 5-9 single scale item scales. Raw scores are then converted to a standardized score with mean 50 and standard deviation 10. The Neuro-QoL short forms used in this study with higher scores representing better outcomes are: Upper Extremity Function, Lower Extremity Function, Cognitive -- General Concerns, Cognitive -- Executive Function, Communication, Positive Affect and Well-Being, Satisfaction with Social Roles and Activities, and Ability to Participate in Social Roles and Activities. The short forms used with lower scores representing better outcomes are: Fatigue, Sleep Disturbance, Anxiety, Depression, and Emotional-Behavioral Dyscontrol.

Outcome measures

Measure	Drug Continuation Arm n=108 Participants Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Standard of Care: Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.	Drug Discontinuation Arm n=113 Participants Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Discontinuation of disease modifying therapy: Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Anxiety	0.2 units on a scale Standard Deviation 6	0.4 units on a scale Standard Deviation 6.2

SECONDARY outcome

Timeframe: Baseline, 18-24 Months, based on time of enrollment

Population: Subjects missing Neuro-QOL at either baseline or at Month 18-24 were excluded from this analysis

The Neuro-QOL Adult PRO short form measures are collected to evaluate self-reported overall quality of life and functioning in patients with a variety of neurological conditions including MS. The Neuro-Qol short form scales consist of 5-9 single scale item scales. Raw scores are then converted to a standardized score with mean 50 and standard deviation 10. The Neuro-QoL short forms used in this study with higher scores representing better outcomes are: Upper Extremity Function, Lower Extremity Function, Cognitive -- General Concerns, Cognitive -- Executive Function, Communication, Positive Affect and Well-Being, Satisfaction with Social Roles and Activities, and Ability to Participate in Social Roles and Activities. The short forms used with lower scores representing better outcomes are: Fatigue, Sleep Disturbance, Anxiety, Depression, and Emotional-Behavioral Dyscontrol.

Outcome measures

Measure	Drug Continuation Arm n=108 Participants Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Standard of Care: Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.	Drug Discontinuation Arm n=112 Participants Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Discontinuation of disease modifying therapy: Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Depression	0.9 units on a scale Standard Deviation 4.9	1.1 units on a scale Standard Deviation 5.5

SECONDARY outcome

Timeframe: Baseline, 18-24 Months, based on time of enrollment

Population: Subjects missing Neuro-QOL at either baseline or at Month 18-24 were excluded from this analysis

The Neuro-QOL Adult PRO short form measures are collected to evaluate self-reported overall quality of life and functioning in patients with a variety of neurological conditions including MS. The Neuro-Qol short form scales consist of 5-9 single scale item scales. Raw scores are then converted to a standardized score with mean 50 and standard deviation 10. The Neuro-QoL short forms used in this study with higher scores representing better outcomes are: Upper Extremity Function, Lower Extremity Function, Cognitive -- General Concerns, Cognitive -- Executive Function, Communication, Positive Affect and Well-Being, Satisfaction with Social Roles and Activities, and Ability to Participate in Social Roles and Activities. The short forms used with lower scores representing better outcomes are: Fatigue, Sleep Disturbance, Anxiety, Depression, and Emotional-Behavioral Dyscontrol.

Outcome measures

Measure	Drug Continuation Arm n=108 Participants Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Standard of Care: Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.	Drug Discontinuation Arm n=113 Participants Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Discontinuation of disease modifying therapy: Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Positive Affect and Well-Being	0 units on a scale Standard Deviation 6.3	-1.2 units on a scale Standard Deviation 8.2

SECONDARY outcome

Timeframe: Baseline, 18-24 Months, based on time of enrollment

Population: Subjects missing Neuro-QOL at either baseline or at Month 18-24 were excluded from this analysis

The Neuro-QOL Adult PRO short form measures are collected to evaluate self-reported overall quality of life and functioning in patients with a variety of neurological conditions including MS. The Neuro-Qol short form scales consist of 5-9 single scale item scales. Raw scores are then converted to a standardized score with mean 50 and standard deviation 10. The Neuro-QoL short forms used in this study with higher scores representing better outcomes are: Upper Extremity Function, Lower Extremity Function, Cognitive -- General Concerns, Cognitive -- Executive Function, Communication, Positive Affect and Well-Being, Satisfaction with Social Roles and Activities, and Ability to Participate in Social Roles and Activities. The short forms used with lower scores representing better outcomes are: Fatigue, Sleep Disturbance, Anxiety, Depression, and Emotional-Behavioral Dyscontrol.

Outcome measures

Measure	Drug Continuation Arm n=109 Participants Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Standard of Care: Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.	Drug Discontinuation Arm n=112 Participants Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Discontinuation of disease modifying therapy: Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Emotional-Behavioral Dyscontrol	-0.2 units on a scale Standard Deviation 7.8	-0.3 units on a scale Standard Deviation 7.2

SECONDARY outcome

Timeframe: Baseline, 18-24 Months, based on time of enrollment

Population: Subjects missing Neuro-QOL at either baseline or at Month 18-24 were excluded from this analysis

The Neuro-QOL Adult PRO short form measures are collected to evaluate self-reported overall quality of life and functioning in patients with a variety of neurological conditions including MS. The Neuro-Qol short form scales consist of 5-9 single scale item scales. Raw scores are then converted to a standardized score with mean 50 and standard deviation 10. The Neuro-QoL short forms used in this study with higher scores representing better outcomes are: Upper Extremity Function, Lower Extremity Function, Cognitive -- General Concerns, Cognitive -- Executive Function, Communication, Positive Affect and Well-Being, Satisfaction with Social Roles and Activities, and Ability to Participate in Social Roles and Activities. The short forms used with lower scores representing better outcomes are: Fatigue, Sleep Disturbance, Anxiety, Depression, and Emotional-Behavioral Dyscontrol.

Outcome measures

Measure	Drug Continuation Arm n=105 Participants Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Standard of Care: Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.	Drug Discontinuation Arm n=113 Participants Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Discontinuation of disease modifying therapy: Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Satisfaction With Social Roles and Activities	1.7 units on a scale Standard Deviation 6.9	-0.7 units on a scale Standard Deviation 5.7

SECONDARY outcome

Timeframe: Baseline, 18-24 Months, based on time of enrollment

Population: Subjects missing Neuro-QOL at either baseline or at Month 18-24 were excluded from this analysis

The Neuro-QOL Adult PRO short form measures are collected to evaluate self-reported overall quality of life and functioning in patients with a variety of neurological conditions including MS. The Neuro-Qol short form scales consist of 5-9 single scale item scales. Raw scores are then converted to a standardized score with mean 50 and standard deviation 10. The Neuro-QoL short forms used in this study with higher scores representing better outcomes are: Upper Extremity Function, Lower Extremity Function, Cognitive -- General Concerns, Cognitive -- Executive Function, Communication, Positive Affect and Well-Being, Satisfaction with Social Roles and Activities, and Ability to Participate in Social Roles and Activities. The short forms used with lower scores representing better outcomes are: Fatigue, Sleep Disturbance, Anxiety, Depression, and Emotional-Behavioral Dyscontrol.

Outcome measures

Measure	Drug Continuation Arm n=105 Participants Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Standard of Care: Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.	Drug Discontinuation Arm n=112 Participants Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Discontinuation of disease modifying therapy: Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Change in Neuro-QoL (Quality of Life) Short Form Scores -- Ability to Participate in Social Roles and Activities	-2.8 units on a scale Standard Deviation 10	-1.6 units on a scale Standard Deviation 11

SECONDARY outcome

Timeframe: Baseline, then every 6 months for up to a maximum of 24 months, based on time of enrollment. The change between baseline and Month 18-24 is reported.

Population: Subjects missing SymptoMScreen at either baseline or at Month 18-24 were excluded from this analysis

SymptoMScreen will be collected to assess overall symptom severity. Participants self-report across multiple neurological domains (mobility, hand function, spasticity, pain, sensory, bladder, fatigue, vision, dizziness, cognition, depression, and anxiety). This scale is a single page, validated measure that allows for quick assessment of multiple symptoms. Single item scores are rated as 0-6 with higher numbers representing increased limitations and symptom severity. Composite score is calculated by summing the single item scores with total score ranges from 0 to 72.

Outcome measures

Measure	Drug Continuation Arm n=113 Participants Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Standard of Care: Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.	Drug Discontinuation Arm n=118 Participants Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Discontinuation of disease modifying therapy: Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Change in SymptoMScreen Composite Score (SymptoMScreen - Overall Symptom Severity).	0 units on a scale Standard Deviation 0.5	0 units on a scale Standard Deviation 0.5

SECONDARY outcome

Timeframe: Baseline, then every 6 months for up to a maximum of 24 months, based on time of enrollment. The change between baseline and Month 18-24 is reported.

Population: Subjects missing PDDS at either baseline or at Month 18-24 were excluded from this analysis

Patient-Determined Disease Steps will be collected to assess changes in disability from the patient's perspective. This outcome measure is a single question. The scores range from 0 to 8, and a participant with a low score has less perceived disability than a participant with a higher score.

Outcome measures

Measure	Drug Continuation Arm n=107 Participants Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Standard of Care: Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.	Drug Discontinuation Arm n=115 Participants Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Discontinuation of disease modifying therapy: Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Change in Patient-Determined Disease Steps (PDDS - Disability).	0 units on a scale Standard Deviation 1.1	0.3 units on a scale Standard Deviation 1.1

SECONDARY outcome

Timeframe: Baseline, then every 6 months for up to a maximum of 24 months, based on time of enrollment. The change between baseline and Month 18-24 is reported.

Population: Subjects missing SDMT at either baseline or at Month 18-24 were excluded from this analysis

The SDMT measures patient attention, concentration, and speed of information processing and has been validated for discriminating patients from controls. Possible scores range from 0 to 110, with higher scores indicating a better outcome.

Outcome measures

Measure	Drug Continuation Arm n=108 Participants Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Standard of Care: Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.	Drug Discontinuation Arm n=112 Participants Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Discontinuation of disease modifying therapy: Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Change in Symbol Digit Modalities Test (SDMT - Cognition).	2.5 units on a scale Standard Deviation 9.6	1.8 units on a scale Standard Deviation 8.8

SECONDARY outcome

Timeframe: Baseline, then every 6 months for up to a maximum of 24 months, based on time of enrollment. The change between baseline and Month 18-24 is reported.

Population: Subjects missing MSIS-29 at either baseline or at Month 18-24 were excluded from this analysis

The Multiple Sclerosis Impact Scale (MSIS-29) will be collected to assess changes in quality of life from the patient's perspective. The MSIS has 29 questions. Each question asks the participant to rank how impacted they are in a certain aspect of their life. The options are 1 through 4. 1 indicates not at all impacted while 4 indicates extremely impacted. The lower the final score, the less impacted the participant is overall. Scores on the physical impact scale range from 20-80 and from 9-36 on the psychological impact scale. We will compare the proportion in each group who have had a change of 7.5 points or more (considered a clinically meaningful change).

Outcome measures

Measure	Drug Continuation Arm n=113 Participants Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Standard of Care: Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.	Drug Discontinuation Arm n=117 Participants Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Discontinuation of disease modifying therapy: Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Evaluation of the Patient's Quality of Life Using the MSIS-29 Scale -- Physical Impact	41 Participants	45 Participants

SECONDARY outcome

Timeframe: Baseline, then every 6 months for up to a maximum of 24 months, based on time of enrollment. The change between baseline and Month 18-24 is reported.

Population: Subjects missing MSIS-29 at either baseline or at Month 18-24 were excluded from this analysis

The Multiple Sclerosis Impact Scale (MSIS-29) will be collected to assess changes in quality of life from the patient's perspective. The MSIS has 29 questions. Each question asks the participant to rank how impacted they are in a certain aspect of their life. The options are 1 through 4. 1 indicates not at all impacted while 4 indicates extremely impacted. The lower the final score, the less impacted the participant is overall. Scores on the physical impact scale range from 20-80 and from 9-36 on the psychological impact scale. We will compare the proportion in each group who have had a change of 7.5 points or more (considered a clinically meaningful change).

Outcome measures

Measure	Drug Continuation Arm n=113 Participants Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Standard of Care: Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.	Drug Discontinuation Arm n=117 Participants Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Discontinuation of disease modifying therapy: Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Evaluation of the Patient's Quality of Life Using the MSIS-29 Scale -- Psychological Impact	44 Participants	43 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, then every 6 months for 2 years with one exception at 18 months.

MRIs will be reviewed to determine the total number of new T2 lesions that develop for each subject over the course of the study. Lesion counts will be performed by the central MRI facility.

Outcome measures

Measure	Drug Continuation Arm n=128 Participants Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Standard of Care: Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.	Drug Discontinuation Arm n=131 Participants Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Discontinuation of disease modifying therapy: Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Total Number of New T2 Lesions on MRI	0 lesions Interval 0.0 to 2.0	0 lesions Interval 0.0 to 5.0

Adverse Events

Drug Continuation Arm

Serious events: 1 serious events

Other events: 66 other events

Deaths: 1 deaths

Drug Discontinuation Arm

Serious events: 1 serious events

Other events: 70 other events

Deaths: 2 deaths

Serious adverse events

Measure	Drug Continuation Arm n=128 participants at risk Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Standard of Care: Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.	Drug Discontinuation Arm n=131 participants at risk Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Discontinuation of disease modifying therapy: Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Nervous system disorders MS relapse	0.78% 1/128 • Number of events 1 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.	0.76% 1/131 • Number of events 1 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.

Other adverse events

Measure	Drug Continuation Arm n=128 participants at risk Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Standard of Care: Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.	Drug Discontinuation Arm n=131 participants at risk Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease. Discontinuation of disease modifying therapy: Participants who will discontinue their current MS drug. No other changes to their treatment occur.
Nervous system disorders MS relapse	0.00% 0/128 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.	2.3% 3/131 • Number of events 3 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.
Nervous system disorders New MS MRI lesion	3.9% 5/128 • Number of events 5 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.	10.7% 14/131 • Number of events 16 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.
Blood and lymphatic system disorders Leg edema	0.78% 1/128 • Number of events 1 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.	0.00% 0/131 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.
Gastrointestinal disorders Abdominal pain	0.78% 1/128 • Number of events 1 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.	0.00% 0/131 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.
Nervous system disorders Leptomeningeal enhancement	0.00% 0/128 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.	0.76% 1/131 • Number of events 1 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.
Blood and lymphatic system disorders Elevated PSA	0.78% 1/128 • Number of events 1 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.	0.00% 0/131 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.
Blood and lymphatic system disorders Abnormal white blood cell count	0.00% 0/128 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.	0.76% 1/131 • Number of events 1 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.
Blood and lymphatic system disorders Abnormal glucose level	0.00% 0/128 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.	0.76% 1/131 • Number of events 1 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.
General disorders Injection reaction	0.00% 0/128 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.	0.76% 1/131 • Number of events 1 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.
Infections and infestations COVID-19 infection	2.3% 3/128 • Number of events 3 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.	5.3% 7/131 • Number of events 7 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.
Renal and urinary disorders Urinary tract infection	13.3% 17/128 • Number of events 27 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.	8.4% 11/131 • Number of events 26 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.
Musculoskeletal and connective tissue disorders Osteoarthritis	7.8% 10/128 • Number of events 10 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.	4.6% 6/131 • Number of events 6 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.
Injury, poisoning and procedural complications Fall	9.4% 12/128 • Number of events 13 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.	9.9% 13/131 • Number of events 14 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.
Infections and infestations Influenza	3.1% 4/128 • Number of events 4 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.	7.6% 10/131 • Number of events 10 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	13.3% 17/128 • Number of events 17 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.	10.7% 14/131 • Number of events 14 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.
Respiratory, thoracic and mediastinal disorders Upper respiratory infection	14.8% 19/128 • Number of events 20 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.	22.9% 30/131 • Number of events 37 • Baseline to end of study (24 months) All SAEs are reported in the table of Serious Adverse Events. Other adverse events exceeding a frequency threshold of 5% are reported. Additionally, AEs were classified as being unrelated to treatment, unlikely to be related to treatment, possibly (\> 50% likelihood) related to treatment, probably related to treatment, or definitely related to treatment. Any AEs deemed probably or definitely related to treatment are reported, even if they did not exceed the 5% threshold.

Additional Information

John R. Corboy, MD

University of Colorado School of Medicine

Phone: 13037242187

Email: john.corboy@cuanschutz.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place