Trial Outcomes & Findings for Study of Evobrutinib in Participants With RMS (evolutionRMS 2) (NCT NCT04338061)

NCT ID: NCT04338061

Last Updated: 2025-03-21

Results Overview

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).

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 1166 participants
• Primary outcome timeframe: Baseline up to 170 weeks
• Results posted on: 2025-03-21

Participant Flow

Participant milestones

Measure	Teriflunomide Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
Double-blind Treatment Period: 156 Weeks STARTED	583	583
Double-blind Treatment Period: 156 Weeks COMPLETED	409	410
Double-blind Treatment Period: 156 Weeks NOT COMPLETED	174	173
Double-blind Extension Period: 96 Weeks STARTED	390	389
Double-blind Extension Period: 96 Weeks COMPLETED	381	377
Double-blind Extension Period: 96 Weeks NOT COMPLETED	9	12

Reasons for withdrawal

Measure	Teriflunomide Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
Double-blind Treatment Period: 156 Weeks Withdrawal by Subject	59	52
Double-blind Treatment Period: 156 Weeks Lack of Efficacy	11	16
Double-blind Treatment Period: 156 Weeks Other Reasons	17	22
Double-blind Treatment Period: 156 Weeks Adverse Event	67	70
Double-blind Treatment Period: 156 Weeks Protocol Non-Compliance	9	8
Double-blind Treatment Period: 156 Weeks Lost to Follow-up	11	3
Double-blind Treatment Period: 156 Weeks Randomized, but not treated	0	2
Double-blind Extension Period: 96 Weeks Withdrawal by Subject	2	1
Double-blind Extension Period: 96 Weeks Lost to Follow-up	1	2
Double-blind Extension Period: 96 Weeks Adverse Event	1	1
Double-blind Extension Period: 96 Weeks Protocol Non-Compliance	1	0
Double-blind Extension Period: 96 Weeks Other Reasons	4	8

Baseline Characteristics

Study of Evobrutinib in Participants With RMS (evolutionRMS 2)

Baseline characteristics by cohort

Measure	Teriflunomide n=583 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=583 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.	Total n=1166 Participants Total of all reporting groups
Age, Continuous	37 Years STANDARD_DEVIATION 9.5 • n=5 Participants	36 Years STANDARD_DEVIATION 9.1 • n=7 Participants	37 Years STANDARD_DEVIATION 9.3 • n=5 Participants
Sex: Female, Male Female	370 Participants n=5 Participants	413 Participants n=7 Participants	783 Participants n=5 Participants
Sex: Female, Male Male	213 Participants n=5 Participants	170 Participants n=7 Participants	383 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity-Hispanic or Latino	30 Participants n=5 Participants	51 Participants n=7 Participants	81 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity-Not Hispanic or Latino	553 Participants n=5 Participants	531 Participants n=7 Participants	1084 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity-Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race-American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race-Asian	17 Participants n=5 Participants	15 Participants n=7 Participants	32 Participants n=5 Participants
Race/Ethnicity, Customized Race-Black or African American	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Race-Multiple	7 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Race-Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race-Other	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Race-Unknown or Not Reported	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Race-White	551 Participants n=5 Participants	556 Participants n=7 Participants	1107 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to 170 weeks

Population: Full Analysis Set (FAS) included all participants who were randomized to study treatment.

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).

Outcome measures

Measure	Teriflunomide n=583 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=583 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
Double Blind Treatment Period (DBTP) and Double Blind Extension (DBE) Period: Annualized Relapse Rate (ARR)	0.11 relapses per year Interval 0.09 to 0.13	0.11 relapses per year Interval 0.09 to 0.13

SECONDARY outcome

Timeframe: Week 96 and Week 156 (combined DBTP and DBE periods)

Population: Full Analysis Set (FAS) included all participants who were randomized to study treatment. The result reported for this outcome measure are the results from data of combined DBTP and DBE periods.

Disability progression was defined as increase in EDSS of greater than or equal to [>=] 1 point from baseline EDSS score, if EDSS score at baseline is 5.0 or less and an increase of >=0.5 point, if the baseline score is 5.5. Disability progression is considered sustained for 12 weeks when the initial increase in the EDSS is confirmed at a regularly scheduled visit at least 12 weeks after the initial documentation of neurological worsening. The total EDSS score ranges from 0 (normal) to 10 (death due to multiple sclerosis). Kaplan-Meier method was used to estimate the percentage of participants without 12-week CDP.

Outcome measures

Measure	Teriflunomide n=583 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=583 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Period: Percentage of Participants Without 12-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) Week 96	88.9 percentage of participants Interval 85.7 to 91.4	91.8 percentage of participants Interval 88.9 to 93.9
DBTP and DBE Period: Percentage of Participants Without 12-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) Week 156	82.3 percentage of participants Interval 76.0 to 87.1	85.0 percentage of participants Interval 77.8 to 90.0

SECONDARY outcome

Timeframe: Week 96 and Week 156 (combined DBTP and DBE periods)

Population: Full Analysis Set (FAS) included all participants who were randomized to study treatment. The result reported for this outcome measure are the results from data of combined DBTP and DBE periods.

Disability progression was defined as increase in EDSS of greater than or equal to [>=] 1 point from baseline EDSS score, if EDSS score at baseline is 5.0 or less and an increase of >=0.5 point, if the baseline score is 5.5. Disability progression is considered sustained for 24 weeks when the initial increase in the EDSS is confirmed at a regularly scheduled visit at least 24 weeks after the initial documentation of neurological worsening. The total EDSS score ranges from 0 (normal) to 10 (death due to multiple sclerosis). Kaplan-Meier method was used to estimate the percentage of participants without 24-week CDP.

Outcome measures

Measure	Teriflunomide n=583 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=583 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Period: Percentage of Participants Without 24-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) Week 96	91.6 percentage of participants Interval 88.7 to 93.8	93.6 percentage of participants Interval 91.0 to 95.5
DBTP and DBE Period: Percentage of Participants Without 24-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) Week 156	89.7 percentage of participants Interval 86.5 to 92.2	90.9 percentage of participants Interval 87.8 to 93.3

SECONDARY outcome

Timeframe: Week 96 and Week 156 (combined DBTP and DBE periods)

Population: Full Analysis Set (FAS) included all participants who were randomized to study treatment. The result reported for this outcome measure are the results from data of combined DBTP and DBE periods.

Disability improvement was defined as a reduction of 1 point from Baseline EDSS score when the Baseline score is >= 2 and less than or equal to [<=] 6 and a reduction of 0.5 point from Baseline EDSS score when the Baseline score is >= 6.5 and <= 9.5. Disability improvement is considered sustained when the initial reduction in the EDSS score is confirmed at a regularly scheduled visit at least 24 weeks after the initial reduction. The total EDSS score ranges from 0 (normal) to 10 (death due to multiple sclerosis). Kaplan-Meier method was used to estimate the percentage of participants with 12-week CDI.

Outcome measures

Measure	Teriflunomide n=583 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=583 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Period: Percentage of Participants With 24-Week Confirmed Disability Improvement (CDI) as Measured by Expanded Disability Status Scale (EDSS) Week 96	11.4 percentage of participants Interval 8.6 to 15.0	7.6 percentage of participants Interval 5.4 to 10.7
DBTP and DBE Period: Percentage of Participants With 24-Week Confirmed Disability Improvement (CDI) as Measured by Expanded Disability Status Scale (EDSS) Week 156	12.5 percentage of participants Interval 9.5 to 16.4	8.4 percentage of participants Interval 6.0 to 11.6

SECONDARY outcome

Timeframe: Baseline, Week 48, Week 96, Week 120, Week 144 and Week 156 (Combined DBTP and DBE periods)

Population: Full Analysis Set (FAS) included all participants who were randomized to study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure. The result reported for this outcome measure are the results from data of combined DBTP and DBE periods.

Physical function was assessed with PROMISnq Short Form v2.0 - Physical Function - Multiple Sclerosis 15a (PROMISnq PF(MS) 15a). PROMISnq PF(MS) 15a assesses a participant's abilities and limitations with respect to everyday physical activities. Results are reported as a T-score. In the general population, T-scores have a mean of 50, standard deviation of 10, and range from 10 to 65. Higher T-scores represent higher physical function. Change from baseline in PROMIS PF score was analyzed using Mixed Effect Model for Repeated Measures (MMRM) to evaluate the result of the 2 periods (DBTP and DBE).

Outcome measures

Measure	Teriflunomide n=572 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=572 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Period: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) Score at Week 48, Week 96, Week 120, Week 144 and Week 156 Week 48	0.25 units on a scale Interval -0.22 to 0.72	0.31 units on a scale Interval -0.16 to 0.78
DBTP and DBE Period: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) Score at Week 48, Week 96, Week 120, Week 144 and Week 156 Week 96	-0.31 units on a scale Interval -0.88 to 0.26	-0.45 units on a scale Interval -1.03 to 0.13
DBTP and DBE Period: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) Score at Week 48, Week 96, Week 120, Week 144 and Week 156 Week 120	-0.56 units on a scale Interval -1.23 to 0.11	-0.19 units on a scale Interval -0.86 to 0.48
DBTP and DBE Period: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) Score at Week 48, Week 96, Week 120, Week 144 and Week 156 Week 144	-0.38 units on a scale Interval -1.12 to 0.35	-0.57 units on a scale Interval -1.31 to 0.17
DBTP and DBE Period: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) Score at Week 48, Week 96, Week 120, Week 144 and Week 156 Week 156	NA units on a scale Week 156 is not evaluable in the modelling due to the lack of participants in some of the covariate categories at that visit.	NA units on a scale Week 156 is not evaluable in the modelling due to the lack of participants in some of the covariate categories at that visit.

SECONDARY outcome

Timeframe: Baseline, Week 48, Week 96, Week 120, Week 144 and Week 156 ((combined DBTP and DBE periods)

Population: Full Analysis Set (FAS) included all participants who were randomized to study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure. The result reported for this outcome measure are the results from data of combined DBTP and DBE periods.

PROMIS Fatigue score was assessed with PROMIS Short Form v1.0 - Fatigue - Multiple Sclerosis 8a (PROMIS Fatigue (MS) 8a). PROMIS Fatigue (MS) 8a assesses level of fatigue and its interference on daily activities. Results are reported as a T-score. In the general population, T-scores have a mean of 50, standard deviation of 10, and range from 33 to 85. Higher T-scores represent higher fatigue. Change from baseline in PROMIS fatigue score was analyzed using Mixed Effect Model for Repeated Measures (MMRM) to evaluate the result of the 2 periods (DBTP and DBE).

Outcome measures

Measure	Teriflunomide n=572 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=572 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Period: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Score at Week 48, Week 96, Week 120, Week 144 and Week 156 Week 48	-2.20 units on a scale Interval -2.81 to -1.6	-2.59 units on a scale Interval -3.19 to -1.98
DBTP and DBE Period: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Score at Week 48, Week 96, Week 120, Week 144 and Week 156 Week 96	-2.17 units on a scale Interval -2.85 to -1.49	-2.12 units on a scale Interval -2.81 to -1.44
DBTP and DBE Period: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Score at Week 48, Week 96, Week 120, Week 144 and Week 156 Week 120	-2.24 units on a scale Interval -3.0 to -1.48	-2.59 units on a scale Interval -3.35 to -1.83
DBTP and DBE Period: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Score at Week 48, Week 96, Week 120, Week 144 and Week 156 Week 144	-2.41 units on a scale Interval -3.35 to -1.48	-2.16 units on a scale Interval -3.1 to -1.22
DBTP and DBE Period: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Score at Week 48, Week 96, Week 120, Week 144 and Week 156 Week 156	-2.21 units on a scale Interval -3.62 to -0.81	-2.34 units on a scale Interval -3.83 to -0.86

SECONDARY outcome

Timeframe: Baseline up to 170 weeks

Population: Full Analysis Set (FAS) included all participants who were randomized to study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Analysis of Gadolinium-positive T1 lesions was done using magnetic resonance imaging (MRI) scans.

Outcome measures

Measure	Teriflunomide n=544 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=544 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Period: Total Number of T1 Gadolinium-positive (Gd+) Lesions	0.29 lesions per scan Interval 0.24 to 0.34	0.51 lesions per scan Interval 0.43 to 0.6

SECONDARY outcome

Timeframe: Baseline up to 170 weeks

Population: Full Analysis Set (FAS) included all participants who were randomized to study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Analysis of new or enlarging T2 lesions rate was done using magnetic resonance imaging (MRI) scans. Negative binomial model for lesion count (summed over scans) includes treatment and covariates based on randomization strata and baseline volume of T2 lesion (continuous), with offset equal to the log of the time in years between the last available MRI scan and the baseline scan.

Outcome measures

Measure	Teriflunomide n=544 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=544 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Period: New or Enlarging T2 Lesions Rate	6.88 lesions per year Interval 6.01 to 7.87	6.17 lesions per year Interval 5.38 to 7.07

SECONDARY outcome

Timeframe: Week 12

Population: Full Analysis Set (FAS) included all participants who were randomized to study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

NfL is a biomarker of neuro-axonal damage whose concentration was assessed in blood at Week 12.

Outcome measures

Measure	Teriflunomide n=544 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=544 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP Period: Neurofilament Light Chain (NfL) Concentration at Week 12	13.09 nanogram per liter (ng/L) Interval 12.69 to 13.5	12.51 nanogram per liter (ng/L) Interval 12.13 to 12.9

SECONDARY outcome

Timeframe: Baseline up to 170 weeks

Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment.

Adverse event (AE): Any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the study drug. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs: those AEs with an onset date on or after the date of first study intervention administration, or AEs present prior to any study intervention administration but exacerbating after. TEAEs included both Serious TEAEs and non-serious TEAEs. AESIs included liver AEs (possible drug-induced, non-infectious, non-alcoholic, and immune-mediated), infections (serious and opportunistic infections), lipase and amylase elevation, and seizure.

Outcome measures

Measure	Teriflunomide n=583 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=581 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Adverse Events of Special Interest (AESIs) Participants with TEAEs	524 Participants	508 Participants
DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Adverse Events of Special Interest (AESIs) Participants with AESIs	144 Participants	135 Participants

SECONDARY outcome

Timeframe: Baseline up to 170 weeks

Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment.

Severity of adverse events (AE) were assessed by the investigator per the National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0. Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with Grades 1, 2, 3, 4 and 5 were reported.

Outcome measures

Measure	Teriflunomide n=583 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=581 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity Participants with Grade 1	41 Participants	59 Participants
DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity Participants with Grade 2	389 Participants	351 Participants
DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity Participants with Grade 3	87 Participants	92 Participants
DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity Participants with Grade 4	7 Participants	6 Participants
DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity Participants with Grade 5	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to 170 weeks

Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Diastolic blood pressure and systolic blood pressure were measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. Changes in vital signs: diastolic blood pressure and systolic blood pressure from baseline up to 170 weeks were reported.

Outcome measures

Measure	Teriflunomide n=457 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=454 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Periods: Change From Baseline in Vital Signs: Diastolic Blood Pressure and Systolic Blood Pressure Systolic Blood Pressure	2.4 millimeter of mercury (mmHg) Standard Deviation 11.0	1.0 millimeter of mercury (mmHg) Standard Deviation 11.50
DBTP and DBE Periods: Change From Baseline in Vital Signs: Diastolic Blood Pressure and Systolic Blood Pressure Diastolic Blood Pressure	1.4 millimeter of mercury (mmHg) Standard Deviation 8.73	-0.5 millimeter of mercury (mmHg) Standard Deviation 8.38

SECONDARY outcome

Timeframe: Baseline up to 170 weeks

Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Pulse rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. Changes in vital signs: pulse rate from baseline up to 170 weeks was reported.

Outcome measures

Measure	Teriflunomide n=457 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=454 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Periods: Change From Baseline in Vital Signs: Pulse Rate	2.2 beats per minute Standard Deviation 10.19	3.0 beats per minute Standard Deviation 10.15

SECONDARY outcome

Timeframe: Baseline up to 170 weeks

Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Respiratory rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. Changes in vital signs: respiratory rate from baseline up to 170 weeks was reported.

Outcome measures

Measure	Teriflunomide n=457 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=454 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Periods: Change From Baseline in Vital Signs: Respiratory Rate	-0.3 breaths per minute Standard Deviation 1.75	-0.5 breaths per minute Standard Deviation 1.87

SECONDARY outcome

Timeframe: Baseline up to 170 weeks

Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Changes in vital signs: weight from baseline up to 170 weeks was reported.

Outcome measures

Measure	Teriflunomide n=457 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=454 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Periods: Change From Baseline in Vital Signs: Weight	-0.51 kilograms (kg) Standard Deviation 5.447	1.06 kilograms (kg) Standard Deviation 5.310

SECONDARY outcome

Timeframe: Baseline up to 170 weeks

Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Temperature was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. Changes in vital signs: Temperature from baseline up to 170 weeks was reported.

Outcome measures

Measure	Teriflunomide n=457 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=454 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Periods: Change From Baseline in Vital Signs: Temperature	-0.02 degree Celsius Standard Deviation 0.340	-0.03 degree Celsius Standard Deviation 0.350

SECONDARY outcome

Timeframe: Baseline up to 170 weeks

Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Heart rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. Changes in vital signs: heart rate from baseline up to 170 weeks was reported.

Outcome measures

Measure	Teriflunomide n=77 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=69 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Periods: Change From Baseline in Electrocardiograms (ECGs): Heart Rate	-0.1 beats per minute Standard Deviation 10.36	2.6 beats per minute Standard Deviation 10.20

SECONDARY outcome

Timeframe: Baseline up to 170 weeks

Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

QT Interval - Fridericia's Correction Formula, PR Interval and QRS Duration was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. Changes in vital signs: QT Interval - Fridericia's Correction Formula, PR Interval and QRS Duration from baseline up to 170 weeks were reported.

Outcome measures

Measure	Teriflunomide n=77 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=69 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Periods: Change From Baseline in Electrocardiograms (ECGs): QT Interval - Fridericia's Correction Formula, PR Interval and QRS Duration QT Interval - Fridericia's Correction Formula	-2.14 milliseconds (msec) Standard Deviation 16.459	-0.07 milliseconds (msec) Standard Deviation 14.935
DBTP and DBE Periods: Change From Baseline in Electrocardiograms (ECGs): QT Interval - Fridericia's Correction Formula, PR Interval and QRS Duration PR Interval	-4.2 milliseconds (msec) Standard Deviation 16.82	-3.1 milliseconds (msec) Standard Deviation 14.51
DBTP and DBE Periods: Change From Baseline in Electrocardiograms (ECGs): QT Interval - Fridericia's Correction Formula, PR Interval and QRS Duration QRS Duration	-2.8 milliseconds (msec) Standard Deviation 6.77	-1.1 milliseconds (msec) Standard Deviation 8.94

SECONDARY outcome

Timeframe: Baseline up to 170 weeks

Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure and "number analyzed"= participants who were evaluable for the specified categories.

Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameters: erythrocytes mean corpuscular HGB concentration and hemoglobin. Changes in hematology parameters: erythrocytes mean corpuscular HGB concentration and hemoglobin from baseline up to 170 weeks were reported.

Outcome measures

Measure	Teriflunomide n=447 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=436 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration Erythrocytes Mean Corpuscular HGB Concentration	0.0 gram per liter (g/L) Standard Deviation 11.07	-1.9 gram per liter (g/L) Standard Deviation 12.42
DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration Hemoglobin	-3.4 gram per liter (g/L) Standard Deviation 11.40	-3.4 gram per liter (g/L) Standard Deviation 11.43

SECONDARY outcome

Timeframe: Baseline up to 170 weeks

Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure and "number analyzed"= participants who were evaluable for the specified categories.

Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameters: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes. Changes in hematology parameters: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes from baseline up to 170 weeks were reported.

Outcome measures

Measure	Teriflunomide n=446 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=437 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes Platelets	-8.4 10^9 cells per liter Standard Deviation 48.38	9.8 10^9 cells per liter Standard Deviation 52.24
DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes Leukocytes	-0.39 10^9 cells per liter Standard Deviation 1.954	0.24 10^9 cells per liter Standard Deviation 1.883
DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes Neutrophils	-0.471 10^9 cells per liter Standard Deviation 1.7550	0.156 10^9 cells per liter Standard Deviation 1.7796
DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes Eosinophils	0.0198 10^9 cells per liter Standard Deviation 0.14809	0.0238 10^9 cells per liter Standard Deviation 0.14945
DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes Basophils	-0.0081 10^9 cells per liter Standard Deviation 0.03882	-0.0042 10^9 cells per liter Standard Deviation 0.03902
DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes Monocytes	0.0797 10^9 cells per liter Standard Deviation 0.19710	0.0772 10^9 cells per liter Standard Deviation 0.20715
DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes Lymphocytes	-0.0241 10^9 cells per liter Standard Deviation 0.57564	0.0311 10^9 cells per liter Standard Deviation 0.57810
DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes Reticulocytes	2.001 10^9 cells per liter Standard Deviation 23.3886	-0.841 10^9 cells per liter Standard Deviation 20.2200

SECONDARY outcome

Timeframe: Baseline up to 170 weeks

Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameter: Hematocrit. Changes in hematology parameter: Hematocrit from baseline up to 170 weeks was reported.

Outcome measures

Measure	Teriflunomide n=442 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=431 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Periods: Change From Baseline in Hematology Parameters: Hematocrit	-0.0107 percentage of cells Standard Deviation 0.03199	-0.0085 percentage of cells Standard Deviation 0.03311

SECONDARY outcome

Timeframe: Baseline up to 170 weeks

Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameter: Erythrocytes Mean Corpuscular Hemoglobin. Changes in hematology parameter: Erythrocytes Mean Corpuscular Hemoglobin from baseline up to 170 weeks was reported.

Outcome measures

Measure	Teriflunomide n=443 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=435 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin	-0.44 picogram Standard Deviation 1.603	-0.93 picogram Standard Deviation 1.941

SECONDARY outcome

Timeframe: Baseline up to 170 weeks

Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameter: Erythrocytes Mean Corpuscular Volume. Changes in hematology parameter: Erythrocytes Mean Corpuscular Volume from baseline up to 170 weeks was reported.

Outcome measures

Measure	Teriflunomide n=441 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=431 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume	-1.48 femtoliters Standard Deviation 4.150	-2.53 femtoliters Standard Deviation 5.217

SECONDARY outcome

Timeframe: Baseline up to 170 weeks

Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure and "number analyzed"= participants who were evaluable for the specified categories.

Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the biochemistry parameters: Bilirubin and Creatinine. Changes in biochemistry parameters: Bilirubin and Creatinine from baseline up to 170 weeks were reported.

Outcome measures

Measure	Teriflunomide n=455 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=446 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Bilirubin and Creatinine Bilirubin	-0.02 micromoles per liter (mcmol/L) Standard Deviation 4.649	0.33 micromoles per liter (mcmol/L) Standard Deviation 4.212
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Bilirubin and Creatinine Creatinine	1.6 micromoles per liter (mcmol/L) Standard Deviation 8.93	2.4 micromoles per liter (mcmol/L) Standard Deviation 12.06

SECONDARY outcome

Timeframe: Baseline up to 170 weeks

Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure and "number analyzed"= participants who were evaluable for the specified categories.

Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the biochemistry parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase. Changes in biochemistry parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase from baseline up to 170 weeks were reported.

Outcome measures

Measure	Teriflunomide n=455 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=446 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase Aspartate Aminotransferase	2.64 units per liter (U/L) Standard Deviation 15.365	1.74 units per liter (U/L) Standard Deviation 13.219
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase Alanine Aminotransferase	4.40 units per liter (U/L) Standard Deviation 33.878	2.75 units per liter (U/L) Standard Deviation 32.018
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase Alkaline Phosphatase	2.32 units per liter (U/L) Standard Deviation 15.875	6.69 units per liter (U/L) Standard Deviation 15.659
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase Amylase	1.3 units per liter (U/L) Standard Deviation 14.42	2.1 units per liter (U/L) Standard Deviation 15.91
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase Lipase	-0.3 units per liter (U/L) Standard Deviation 18.35	2.3 units per liter (U/L) Standard Deviation 17.26
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase Gamma Glutamyl Transferase	3.71 units per liter (U/L) Standard Deviation 26.084	1.98 units per liter (U/L) Standard Deviation 20.207
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase Lactate Dehydrogenase	7.08 units per liter (U/L) Standard Deviation 27.049	-5.41 units per liter (U/L) Standard Deviation 27.637

SECONDARY outcome

Timeframe: Baseline up to 170 weeks

Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure and "number analyzed"= participants who were evaluable for the specified categories.

Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the biochemistry parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium. Changes in biochemistry parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium from baseline up to 170 weeks were reported.

Outcome measures

Measure	Teriflunomide n=450 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=446 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium Sodium	0.9286 millimole per liter (mmol/L) Standard Deviation 2.56796	0.7750 millimole per liter (mmol/L) Standard Deviation 3.21185
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium Potassium	0.0405 millimole per liter (mmol/L) Standard Deviation 0.48750	0.0376 millimole per liter (mmol/L) Standard Deviation 0.44331
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium Calcium	-0.006 millimole per liter (mmol/L) Standard Deviation 0.1197	-0.008 millimole per liter (mmol/L) Standard Deviation 0.1121
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium Magnesium	-0.002 millimole per liter (mmol/L) Standard Deviation 0.0656	-0.006 millimole per liter (mmol/L) Standard Deviation 0.0667
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium Glucose	0.09 millimole per liter (mmol/L) Standard Deviation 0.949	0.16 millimole per liter (mmol/L) Standard Deviation 0.812
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium Chloride	2.3 millimole per liter (mmol/L) Standard Deviation 3.30	2.1 millimole per liter (mmol/L) Standard Deviation 3.53
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium Urea Nitrogen	0.126 millimole per liter (mmol/L) Standard Deviation 1.2759	0.122 millimole per liter (mmol/L) Standard Deviation 1.1651
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium Phosphate	-0.047 millimole per liter (mmol/L) Standard Deviation 0.1944	-0.024 millimole per liter (mmol/L) Standard Deviation 0.1799
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium Bicarbonate	0.44 millimole per liter (mmol/L) Standard Deviation 2.592	0.17 millimole per liter (mmol/L) Standard Deviation 2.980
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium Corrected Calcium	0.0290 millimole per liter (mmol/L) Standard Deviation 0.10405	0.0292 millimole per liter (mmol/L) Standard Deviation 0.09775

SECONDARY outcome

Timeframe: Baseline up to 170 weeks

Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure and "number analyzed"= participants who were evaluable for the specified categories.

Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the biochemistry parameters: Total Protein and Albumin. Changes in biochemistry parameters: Total Protein and Albumin from baseline up to 170 weeks were reported.

Outcome measures

Measure	Teriflunomide n=448 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=444 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Total Protein and Albumin Total protein	-1.31 gram per liter (g/L) Standard Deviation 4.905	-0.59 gram per liter (g/L) Standard Deviation 4.998
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Total Protein and Albumin Albumin	-1.75 gram per liter (g/L) Standard Deviation 3.497	-1.83 gram per liter (g/L) Standard Deviation 3.287

SECONDARY outcome

Timeframe: Baseline up to 170 weeks

Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the biochemistry parameter: Glomerular Filtration Rate. Changes in biochemistry parameter: Glomerular Filtration Rate from baseline up to 170 weeks were reported. The Glomerular Filtration Rate was measured as milliliter per minute per 1.73 square meter (mL/min/1.73m^2).

Outcome measures

Measure	Teriflunomide n=360 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=351 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Glomerular Filtration Rate	-4.7 mL/min/1.73m^2 Standard Deviation 13.41	-5.7 mL/min/1.73m^2 Standard Deviation 13.81

SECONDARY outcome

Timeframe: Baseline up to 170 weeks

Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Urine samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the urinalyses parameter: pH. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Changes in urinalyses parameter: pH from baseline up to 170 weeks was reported.

Outcome measures

Measure	Teriflunomide n=442 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=438 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Periods: Change From Baseline in Urinalyses Parameter: Potential of Hydrogen (pH) of Urine	-0.03 pH Standard Deviation 0.936	-0.04 pH Standard Deviation 0.973

SECONDARY outcome

Timeframe: Baseline up to 170 weeks

Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Urine samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the urinalyses parameter: Specific Gravity of Urine. Changes in urinalyses parameter: Specific Gravity of Urine from baseline up to 170 weeks was reported.

Outcome measures

Measure	Teriflunomide n=436 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=428 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Periods: Change From Baseline in Urinalyses Parameter: Specific Gravity of Urine	-0.0015 Kilogram per cubic meter Standard Deviation 0.04460	-0.0017 Kilogram per cubic meter Standard Deviation 0.03748

SECONDARY outcome

Timeframe: At Week 170

Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Absolute Concentrations serum levels of IgG, IgA, IgM were assessed.

Outcome measures

Measure	Teriflunomide n=319 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=341 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Periods: Absolute Concentrations of Immunoglobulin (Ig) Levels IgA	1.899 gram per liter (g/L) Standard Deviation 0.7787	2.581 gram per liter (g/L) Standard Deviation 1.1201
DBTP and DBE Periods: Absolute Concentrations of Immunoglobulin (Ig) Levels IgG	10.082 gram per liter (g/L) Standard Deviation 2.1551	10.990 gram per liter (g/L) Standard Deviation 2.4844
DBTP and DBE Periods: Absolute Concentrations of Immunoglobulin (Ig) Levels IgM	1.251 gram per liter (g/L) Standard Deviation 0.6445	1.196 gram per liter (g/L) Standard Deviation 0.6151

SECONDARY outcome

Timeframe: Baseline up to 170 weeks

Population: Safety (SAF) analysis set included all participants who received at least one dose of study treatment. Here, Overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Change from baseline serum levels of IgG, IgA, IgM were assessed.

Outcome measures

Measure	Teriflunomide n=319 Participants Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=339 Participants Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
DBTP and DBE Periods: Change From Baseline in Immunoglobulin (Ig) Levels IgA	-0.203 gram per liter (g/L) Standard Deviation 0.5704	0.500 gram per liter (g/L) Standard Deviation 0.7197
DBTP and DBE Periods: Change From Baseline in Immunoglobulin (Ig) Levels IgG	-0.645 gram per liter (g/L) Standard Deviation 1.6188	0.146 gram per liter (g/L) Standard Deviation 1.8712
DBTP and DBE Periods: Change From Baseline in Immunoglobulin (Ig) Levels IgM	-0.167 gram per liter (g/L) Standard Deviation 0.5094	-0.175 gram per liter (g/L) Standard Deviation 0.3888

Adverse Events

Teriflunomide

Serious events: 37 serious events

Other events: 455 other events

Deaths: 0 deaths

Evobrutinib

Serious events: 51 serious events

Other events: 409 other events

Deaths: 0 deaths

Serious adverse events

Measure	Teriflunomide n=583 participants at risk Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=581 participants at risk Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
Infections and infestations Respiratory tract infection viral	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Infections and infestations Salpingo-oophoritis	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Infections and infestations Tonsillitis	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Infections and infestations Urinary tract infection	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.34% 2/581 • Number of events 3 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Accidental overdose	0.34% 2/583 • Number of events 2 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Bladder injury	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Carbon monoxide poisoning	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Concussion	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Craniocerebral injury	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Facial bones fracture	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Foot fracture	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Head injury	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Cardiac disorders Acute myocardial infarction	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Cardiac disorders Myocardial infarction	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Eye disorders Chalazion	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Ileus spastic	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Hepatobiliary disorders Cholecystitis acute	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Hepatobiliary disorders Cholelithiasis	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Hepatobiliary disorders Drug-induced liver injury	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Hepatobiliary disorders Hepatitis	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Infections and infestations Acute sinusitis	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Infections and infestations Appendicitis	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.34% 2/581 • Number of events 2 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Infections and infestations COVID-19	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.34% 2/581 • Number of events 2 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Infections and infestations COVID-19 pneumonia	0.34% 2/583 • Number of events 2 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.34% 2/581 • Number of events 2 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Infections and infestations Cholecystitis infective	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Infections and infestations Chronic tonsillitis	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Infections and infestations Pyelonephritis acute	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Infections and infestations Renal abscess	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Incisional hernia	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Joint injury	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Muscle injury	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Musculoskeletal injury	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Pelvic fracture	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Scar	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Urinary tract injury	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Vascular pseudoaneurysm	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Investigations Alanine aminotransferase increased	0.51% 3/583 • Number of events 3 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	1.2% 7/581 • Number of events 7 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Investigations Aspartate aminotransferase increased	0.34% 2/583 • Number of events 2 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.52% 3/581 • Number of events 3 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Investigations SARS-CoV-2 test positive	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Electrolyte imbalance	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Symphysiolysis	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangioma of liver	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary thyroid cancer	0.34% 2/583 • Number of events 2 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Synovial sarcoma	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.34% 2/583 • Number of events 2 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.69% 4/581 • Number of events 4 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Nervous system disorders Autonomic neuropathy	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Nervous system disorders Epilepsy	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Nervous system disorders Headache	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Nervous system disorders Ischaemic stroke	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Nervous system disorders Lumbosacral radiculopathy	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.34% 2/581 • Number of events 2 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Nervous system disorders Migraine	0.17% 1/583 • Number of events 2 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Nervous system disorders Multiple sclerosis relapse	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.52% 3/581 • Number of events 3 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Nervous system disorders Syncope	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Psychiatric disorders Alcoholism	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Psychiatric disorders Depression	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Psychiatric disorders Mental disorder	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Psychiatric disorders Mood disorder due to a general medical condition	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Psychiatric disorders Neuropsychiatric symptoms	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Psychiatric disorders Suicidal ideation	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Psychiatric disorders Suicide attempt	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Reproductive system and breast disorders Abnormal uterine bleeding	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Reproductive system and breast disorders Cervical polyp	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Reproductive system and breast disorders Endometrial hyperplasia	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Reproductive system and breast disorders Endometriosis	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Reproductive system and breast disorders Genital haemorrhage	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Reproductive system and breast disorders Haemorrhagic ovarian cyst	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Reproductive system and breast disorders Uterine haemorrhage	0.17% 1/583 • Number of events 2 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Reproductive system and breast disorders Uterine polyp	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Emphysema	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Paranasal sinus inflammation	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pneumothorax spontaneous	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.17% 1/583 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.00% 0/581 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Respiratory arrest	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Social circumstances Miscarriage of partner	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Social circumstances Pregnancy of partner	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Vascular disorders Subgaleal haematoma	0.00% 0/583 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	0.17% 1/581 • Number of events 1 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.

Other adverse events

Measure	Teriflunomide n=583 participants at risk Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period.	Evobrutinib n=581 participants at risk Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period.
Blood and lymphatic system disorders Anaemia	3.9% 23/583 • Number of events 35 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	5.9% 34/581 • Number of events 54 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Blood and lymphatic system disorders Neutropenia	8.1% 47/583 • Number of events 112 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	3.8% 22/581 • Number of events 33 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Diarrhoea	8.1% 47/583 • Number of events 59 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	4.1% 24/581 • Number of events 28 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Nausea	6.2% 36/583 • Number of events 39 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	5.0% 29/581 • Number of events 39 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
General disorders Fatigue	8.1% 47/583 • Number of events 66 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	6.4% 37/581 • Number of events 46 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Infections and infestations COVID-19	20.8% 121/583 • Number of events 139 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	18.1% 105/581 • Number of events 119 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Infections and infestations Nasopharyngitis	11.5% 67/583 • Number of events 103 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	10.0% 58/581 • Number of events 89 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Infections and infestations Respiratory tract infection viral	6.3% 37/583 • Number of events 52 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	4.0% 23/581 • Number of events 36 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Infections and infestations Upper respiratory tract infection	7.7% 45/583 • Number of events 81 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	9.5% 55/581 • Number of events 83 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Infections and infestations Urinary tract infection	5.7% 33/583 • Number of events 46 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	6.7% 39/581 • Number of events 49 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Investigations Alanine aminotransferase increased	21.6% 126/583 • Number of events 227 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	17.0% 99/581 • Number of events 168 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Investigations Aspartate aminotransferase increased	13.7% 80/583 • Number of events 123 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	10.5% 61/581 • Number of events 84 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Investigations Gamma-glutamyltransferase increased	5.0% 29/583 • Number of events 70 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	5.3% 31/581 • Number of events 37 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Investigations Lipase increased	5.7% 33/583 • Number of events 39 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	5.7% 33/581 • Number of events 55 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Investigations Lymphocyte count decreased	6.7% 39/583 • Number of events 73 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	4.6% 27/581 • Number of events 40 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Investigations Neutrophil count decreased	15.8% 92/583 • Number of events 156 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	6.9% 40/581 • Number of events 42 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Investigations White blood cell count decreased	10.8% 63/583 • Number of events 122 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	4.0% 23/581 • Number of events 39 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Back pain	10.5% 61/583 • Number of events 79 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	8.4% 49/581 • Number of events 63 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	5.5% 32/583 • Number of events 40 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	5.2% 30/581 • Number of events 46 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Nervous system disorders Headache	17.7% 103/583 • Number of events 169 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	16.5% 96/581 • Number of events 198 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Alopecia	14.4% 84/583 • Number of events 87 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.	6.0% 35/581 • Number of events 38 • Baseline up to 170 weeks Safety (SAF) analysis set included all participants who received at least one dose of study treatment.

Additional Information

Communication Center

Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Email: service@emdgroup.com

Results disclosure agreements

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