Trial Outcomes & Findings for Characterize Flu-like Symptoms in Relapsing Multiple Sclerosis Patients Transitioning From Non-Pegylated Interferon Beta (IFN-β) Therapies to Peginterferon Beta-1a (BIIB017) (NCT NCT01939002)

Results Overview

The total Flu-like Symptoms Score (FLS-S) is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. New or increased FLS is defined as an FLS overall score of 2 points or greater over Screening. Pre-dose data were not used; up to 48-hour data after dosing were used. Overall score was imputed as the average score after dose.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

251 participants

Primary outcome timeframe

during the first 8 weeks of treatment

Results posted on

2017-01-25

Participant Flow

Of the 251 participants who entered into the run-in period of non-pegylated interferon (IFN) therapy, a total of 201 were randomized.

Participant milestones

Participant milestones
Measure	BIIB017 Plus Current FLS Therapy Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus current FLS management regimen as determined by the clinician.	BIIB017 Plus Naproxen Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.
Overall Study STARTED	103	98
Overall Study COMPLETED	84	80
Overall Study NOT COMPLETED	19	18

Reasons for withdrawal

Reasons for withdrawal
Measure	BIIB017 Plus Current FLS Therapy Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus current FLS management regimen as determined by the clinician.	BIIB017 Plus Naproxen Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.
Overall Study Adverse Event	13	13
Overall Study Withdrawal by Subject	5	3
Overall Study Other	1	2

Baseline Characteristics

Characterize Flu-like Symptoms in Relapsing Multiple Sclerosis Patients Transitioning From Non-Pegylated Interferon Beta (IFN-β) Therapies to Peginterferon Beta-1a (BIIB017)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BIIB017 Plus Current FLS Therapy n=103 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus current FLS management regimen as determined by the clinician.	BIIB017 Plus Naproxen n=98 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Total n=201 Participants Total of all reporting groups
Age, Continuous	49.76 years STANDARD_DEVIATION 10.32 • n=5 Participants	49.88 years STANDARD_DEVIATION 9.45 • n=7 Participants	49.82 years STANDARD_DEVIATION 9.88 • n=5 Participants
Gender Female	84 Participants n=5 Participants	79 Participants n=7 Participants	163 Participants n=5 Participants
Gender Male	19 Participants n=5 Participants	19 Participants n=7 Participants	38 Participants n=5 Participants

PRIMARY outcome

Timeframe: during the first 8 weeks of treatment

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment and had efficacy data in both the 4-week run-in period and the post-baseline treatment period.

The total Flu-like Symptoms Score (FLS-S) is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. New or increased FLS is defined as an FLS overall score of 2 points or greater over Screening. Pre-dose data were not used; up to 48-hour data after dosing were used. Overall score was imputed as the average score after dose.

Outcome measures

Outcome measures
Measure	Overall Population n=194 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Percentage of Participants Experiencing New or Increased FLS During the First 8 Weeks: Overall Population	10.3 percentage of participants	—	—

SECONDARY outcome

Timeframe: during the first 8 weeks of treatment

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment and had efficacy data in both the 4-week run-in period and the post-baseline treatment period.

The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. New or increased FLS is defined as an FLS overall score of 2 points or greater over Screening. Pre-dose data were not used; up to 48-hour data after dosing were used. Overall score was imputed as the average score after dose.

Outcome measures

Outcome measures
Measure	Overall Population n=100 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen n=94 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Percentage of Participants Experiencing New or Increased FLS During the First 8 Weeks: Between FLS Management Arms	13 percentage of participants	7.4 percentage of participants	—

SECONDARY outcome

Timeframe: 4-week run-in period, first 8 weeks of treatment, 48 weeks of treatment

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment and had efficacy data in both the 4-week run-in period and the post-baseline treatment period.

Any FLS is defined as an FLS-S total score \> 0. The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. 4WRI=4-week run-in; F8W=first 8 weeks; 48W=48 weeks.

Outcome measures

Outcome measures
Measure	Overall Population n=100 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen n=94 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population n=194 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Percentage of Participants With Any FLS in the 4-Week Run-In Period, During the First 8 Weeks of Treatment, and During 48 Weeks of Treatment F8W	91 percentage of participants	88.3 percentage of participants	89.7 percentage of participants
Percentage of Participants With Any FLS in the 4-Week Run-In Period, During the First 8 Weeks of Treatment, and During 48 Weeks of Treatment 4WRI	88 percentage of participants	91.5 percentage of participants	89.7 percentage of participants
Percentage of Participants With Any FLS in the 4-Week Run-In Period, During the First 8 Weeks of Treatment, and During 48 Weeks of Treatment 48W	95 percentage of participants	94.7 percentage of participants	94.8 percentage of participants

SECONDARY outcome

Timeframe: 4-week run-in period, first 8 weeks of treatment

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment and had efficacy data in both the 4-week run-in period and the post-baseline treatment period.

Any FLS is defined as an FLS-S total score \> 0. The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. Pre-dose data not were used. Data up to 48-hours after dosing were used. Total score was imputed as the highest score after dose. 4WRI=4-week run-in period; F8W=first 8 weeks.

Outcome measures

Outcome measures
Measure	Overall Population n=100 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen n=94 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population n=194 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Shift in Percentage of Participants With Any FLS From 4-Week Run-In Period to the First 8 Weeks Without FLS in 4WRI / With FLS during F8W	6.00 percentage of participants	5.32 percentage of participants	5.67 percentage of participants
Shift in Percentage of Participants With Any FLS From 4-Week Run-In Period to the First 8 Weeks Without FLS in 4WRI / Without FLS during F8W	6.00 percentage of participants	3.19 percentage of participants	4.64 percentage of participants
Shift in Percentage of Participants With Any FLS From 4-Week Run-In Period to the First 8 Weeks With FLS in 4WRI / With FLS during F8W	85.00 percentage of participants	82.98 percentage of participants	84.02 percentage of participants
Shift in Percentage of Participants With Any FLS From 4-Week Run-In Period to the First 8 Weeks With FLS in 4WRI / Without FLS during F8W	3.00 percentage of participants	8.51 percentage of participants	5.67 percentage of participants

SECONDARY outcome

Timeframe: 4-week run-in period, 48 weeks of treatment

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment and had efficacy data in both the 4-week run-in period and the post-baseline treatment period.

Any FLS is defined as an FLS-S total score \> 0. The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. Pre-dose data not were used. Data up to 48-hours after dosing were used. Total score was imputed as the highest score after dose. 4WRI=4-week run-in period; 48W=48 weeks.

Outcome measures

Outcome measures
Measure	Overall Population n=100 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen n=94 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population n=194 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Shift in Percentage of Participants With Any FLS From 4-Week Run-In Period to 48 Weeks With FLS in 4WRI / With FLS during 48W	86.00 percentage of participants	87.23 percentage of participants	86.60 percentage of participants
Shift in Percentage of Participants With Any FLS From 4-Week Run-In Period to 48 Weeks With FLS in 4WRI / Without FLS during 48W	2.00 percentage of participants	4.26 percentage of participants	3.09 percentage of participants
Shift in Percentage of Participants With Any FLS From 4-Week Run-In Period to 48 Weeks Without FLS in 4WRI / With FLS during 48W	9.00 percentage of participants	7.45 percentage of participants	8.25 percentage of participants
Shift in Percentage of Participants With Any FLS From 4-Week Run-In Period to 48 Weeks Without FLS in 4WRI / Without FLS during 48W	3.00 percentage of participants	1.06 percentage of participants	2.06 percentage of participants

SECONDARY outcome

Timeframe: 4-week run-in period, first 8 weeks of treatment

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment and had efficacy data in both the 4-week run-in period and the post-baseline treatment period.

The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. 4WRI=4-week run-in period; F8W=first 8 weeks.

Outcome measures

Outcome measures
Measure	Overall Population n=100 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen n=94 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population n=194 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Summary of Severity of FLS (Per FLS-S) in the First 8 Weeks Compared to 4-Week Run-In Period Between Arms Severity of FLS in 4WRI	1.198 units on a scale Standard Deviation 1.224	1.05 units on a scale Standard Deviation 1.02	1.126 units on a scale Standard Deviation 1.129
Summary of Severity of FLS (Per FLS-S) in the First 8 Weeks Compared to 4-Week Run-In Period Between Arms Severity of FLS in F8W	1.311 units on a scale Standard Deviation 1.185	1.036 units on a scale Standard Deviation 0.951	1.178 units on a scale Standard Deviation 1.084
Summary of Severity of FLS (Per FLS-S) in the First 8 Weeks Compared to 4-Week Run-In Period Between Arms Mean Change from 4WRI to F8W	0.113 units on a scale Standard Deviation 0.67	-0.013 units on a scale Standard Deviation 0.581	0.052 units on a scale Standard Deviation 0.63

SECONDARY outcome

Timeframe: 4-week run-in period, 48 weeks of treatment

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment and had efficacy data in both the 4-week run-in period and the post-baseline treatment period.

The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. 4WRI=4-week run-in period; 48W=48 weeks.

Outcome measures

Outcome measures
Measure	Overall Population n=100 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen n=94 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population n=194 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Summary of Severity of FLS (Per FLS-S) in the 48 Weeks of Treatment Compared to 4-Week Run-In Period Between Arms Severity of FLS in 4WRI	1.2 units on a scale Standard Deviation 1.22	1.05 units on a scale Standard Deviation 1.02	1.13 units on a scale Standard Deviation 1.13
Summary of Severity of FLS (Per FLS-S) in the 48 Weeks of Treatment Compared to 4-Week Run-In Period Between Arms Severity of FLS in 48W	1.28 units on a scale Standard Deviation 1.19	0.98 units on a scale Standard Deviation 1.00	1.14 units on a scale Standard Deviation 1.11
Summary of Severity of FLS (Per FLS-S) in the 48 Weeks of Treatment Compared to 4-Week Run-In Period Between Arms Mean Change from 4WRI to 48W	0.08 units on a scale Standard Deviation 0.83	-0.07 units on a scale Standard Deviation 0.7	0.01 units on a scale Standard Deviation 0.77

SECONDARY outcome

Timeframe: 4-week run-in period, first 8 weeks of treatment

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment and had efficacy data in both the 4-week run-in period and the post-baseline treatment period; n=number of subjects assessed at the given timepoint.

Duration of FLS for a treatment was defined as the sum of hours from the time of treatment to 48 hours with an FLS-S score \> 0. The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. If an FLS is \> 0 at an evaluation time, 6 hours were counted as the duration assuming the event started from previous evaluation time. Average duration of FLS for the first 8 weeks was defined as the mean duration from Weeks 0, 2, 4, 6, and 8. 4WRI=4-week run-in period; F8W=first 8 weeks.

Outcome measures

Outcome measures
Measure	Overall Population n=100 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen n=94 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population n=194 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Summary of Average Duration of FLS in the First 8 Weeks of Treatment Average duration in 4WRI; n=88, 86, 174	16 hours Interval 6.0 to 33.38	12.8 hours Interval 6.0 to 42.86	13.75 hours Interval 6.0 to 42.86
Summary of Average Duration of FLS in the First 8 Weeks of Treatment Average duration in F8W; n=91, 83, 174	18 hours Interval 6.0 to 40.8	18 hours Interval 6.0 to 43.5	18 hours Interval 6.0 to 43.5
Summary of Average Duration of FLS in the First 8 Weeks of Treatment Change from 4WRI to F8W; n=85, 78, 163	2.1 hours Interval -16.5 to 18.4	3.8 hours Interval -10.5 to 20.4	3 hours Interval -16.5 to 20.4

SECONDARY outcome

Timeframe: 4-week run-in period, 48 weeks of treatment

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment and had efficacy data in both the 4-week run-in period and the post-baseline treatment period; n=number of subjects assessed at the given timepoint.

Duration of FLS for a treatment was defined as the sum of hours from the time of treatment to 48 hours with a FLS-S score \> 0. The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. If a FLS is \> 0 at an evaluation time, 6 hours were counted as the duration assuming the event started from previous evaluation time. Average duration of FLS for the first 8 weeks was defined as the mean duration from Weeks 0, 2, 4, 6, and 8. 4WRI=4-week run-in period; 48W=48 weeks.

Outcome measures

Outcome measures
Measure	Overall Population n=100 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen n=94 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population n=194 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Summary of Average Duration of FLS in the 48 Weeks of Treatment Average duration in 4WRI; n=88, 86, 174	16 hours Interval 6.0 to 33.38	12.8 hours Interval 6.0 to 42.86	13.75 hours Interval 6.0 to 42.86
Summary of Average Duration of FLS in the 48 Weeks of Treatment Change from 4WRI to 48W; n=86, 82, 168	2.82 hours Interval -19.57 to 17.83	2 hours Interval -10.0 to 14.88	2.16 hours Interval -19.57 to 17.83
Summary of Average Duration of FLS in the 48 Weeks of Treatment Average duration in 48W; n=95, 89, 184	16.75 hours Interval 6.0 to 38.09	16.96 hours Interval 6.0 to 39.0	16.96 hours Interval 6.0 to 39.0

SECONDARY outcome

Timeframe: 4-week run-in period, first 8 weeks of treatment

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment and had efficacy data in both the 4-week run-in period and the post-baseline treatment period; n=number of participants assessed at the given timepoint.

Participants reported the effectiveness of their FLS management regimen on a 100-mm VAS between not effective (0) and very effective (100). 4WRI=4-week run-in period; F8W=first 8 weeks.

Outcome measures

Outcome measures
Measure	Overall Population n=100 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen n=94 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population n=194 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Summary of FLS-Visual Analogue Scale (VAS) During the First 8 Weeks of Treatment Compared to 4-Week Run-In Period: Effectiveness of FLS Treatment Effectiveness in 4WRI; n=91, 86, 177	64.5 units on a scale Standard Deviation 27.952	66.398 units on a scale Standard Deviation 28.855	65.422 units on a scale Standard Deviation 28.329
Summary of FLS-Visual Analogue Scale (VAS) During the First 8 Weeks of Treatment Compared to 4-Week Run-In Period: Effectiveness of FLS Treatment Effectiveness in F8W; n=96, 91, 187	69.695 units on a scale Standard Deviation 22.423	74.253 units on a scale Standard Deviation 23.85	71.913 units on a scale Standard Deviation 23.179
Summary of FLS-Visual Analogue Scale (VAS) During the First 8 Weeks of Treatment Compared to 4-Week Run-In Period: Effectiveness of FLS Treatment Change from 4WRI to F8W; n=87, 83, 170	6.525 units on a scale Standard Deviation 23.271	5.694 units on a scale Standard Deviation 29.151	6.119 units on a scale Standard Deviation 26.231

SECONDARY outcome

Timeframe: 4-week run-in period, first 8 weeks of treatment

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment and had efficacy data in both the 4-week run-in period and the post-baseline treatment period; n=number of participants assessed at the given timepoint.

Participants reported their satisfaction with the effectiveness of their FLS management regimen on a 100-mm VAS between not satisfied (0) and very satisfied (100). 4WRI=4-week run-in period; F8W=first 8 weeks.

Outcome measures

Outcome measures
Measure	Overall Population n=100 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen n=94 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population n=194 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Summary of FLS-VAS During the First 8 Weeks of Treatment Compared to 4-Week Run-In Period: Satisfaction With FLS Treatment Satisfaction in F8W; n=96, 91, 187	71.153 units on a scale Standard Deviation 21.884	74.684 units on a scale Standard Deviation 23.671	72.871 units on a scale Standard Deviation 22.778
Summary of FLS-VAS During the First 8 Weeks of Treatment Compared to 4-Week Run-In Period: Satisfaction With FLS Treatment Satisfaction in 4WRI; n=91, 86, 177	68.654 units on a scale Standard Deviation 26.574	72.778 units on a scale Standard Deviation 23.817	70.658 units on a scale Standard Deviation 25.285
Summary of FLS-VAS During the First 8 Weeks of Treatment Compared to 4-Week Run-In Period: Satisfaction With FLS Treatment Change from 4WRI to F8W; n=87, 83, 170	3.715 units on a scale Standard Deviation 23.307	0.759 units on a scale Standard Deviation 24.729	2.272 units on a scale Standard Deviation 23.986

SECONDARY outcome

Timeframe: 4-week run-in period, 48 weeks of treatment

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment and had efficacy data in both the 4-week run-in period and the post-baseline treatment period; n=number of participants assessed at the given timepoint.

Participants reported the effectiveness of their FLS management regimen on a 100-mm VAS between not effective (0) and very effective (100). 4WRI=4-week run-in period; 48W=48 weeks.

Outcome measures

Outcome measures
Measure	Overall Population n=100 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen n=94 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population n=194 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Summary of FLS-VAS During the 48 Weeks of Treatment Compared to 4-Week Run-In Period: Effectiveness of FLS Treatment Change from 4WRI to 48W; n=90, 86, 176	6.803 units on a scale Standard Deviation 24.182	8.042 units on a scale Standard Deviation 27.206	7.408 units on a scale Standard Deviation 25.638
Summary of FLS-VAS During the 48 Weeks of Treatment Compared to 4-Week Run-In Period: Effectiveness of FLS Treatment Effectiveness in 4WRI; n=91, 86, 177	64.5 units on a scale Standard Deviation 27.952	66.398 units on a scale Standard Deviation 28.855	65.422 units on a scale Standard Deviation 28.329
Summary of FLS-VAS During the 48 Weeks of Treatment Compared to 4-Week Run-In Period: Effectiveness of FLS Treatment Effectiveness in 48W; n=99, 94, 193	70.547 units on a scale Standard Deviation 21.657	75.416 units on a scale Standard Deviation 21.28	72.918 units on a scale Standard Deviation 21.557

SECONDARY outcome

Timeframe: 4-week run-in period, 48 weeks of treatment

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment and had efficacy data in both the 4-week run-in period and the post-baseline treatment period; n=number of participants assessed at the given timepoint.

Participants reported their satisfaction with the effectiveness of their FLS management regimen on a 100-mm VAS between not satisfied (0) and very satisfied (100). 4WRI=4-week run-in period; 48W=48 weeks.

Outcome measures

Outcome measures
Measure	Overall Population n=100 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen n=94 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population n=194 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Summary of FLS-VAS During the 48 Weeks of Treatment Compared to 4-Week Run-In Period: Satisfaction With FLS Treatment Satisfaction in 4WRI; n=91, 86, 177	68.654 units on a scale Standard Deviation 26.574	72.778 units on a scale Standard Deviation 23.817	70.658 units on a scale Standard Deviation 25.285
Summary of FLS-VAS During the 48 Weeks of Treatment Compared to 4-Week Run-In Period: Satisfaction With FLS Treatment Satisfaction in 48W; n=99, 94, 193	72.192 units on a scale Standard Deviation 21.053	76.061 units on a scale Standard Deviation 21.075	74.076 units on a scale Standard Deviation 21.098
Summary of FLS-VAS During the 48 Weeks of Treatment Compared to 4-Week Run-In Period: Satisfaction With FLS Treatment Change from 4WRI to 48W; n=90, 86, 176	4.607 units on a scale Standard Deviation 22.43	2.274 units on a scale Standard Deviation 21.874	3.467 units on a scale Standard Deviation 22.128

SECONDARY outcome

Timeframe: during the first 8 weeks of treatment

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment and had efficacy data in both the 4-week run-in period and the post-baseline treatment period; n=number of subjects assessed at the given timepoint.

Outcome measures

Outcome measures
Measure	Overall Population n=100 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen n=94 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Percentage of Participants Requiring Additional FLS Management Regimen to Relieve BIIB017-related FLS Used additional regimen, Weeks 5-6; n=63, 76	0 percentage of participants	2.6 percentage of participants	—
Percentage of Participants Requiring Additional FLS Management Regimen to Relieve BIIB017-related FLS No additional regimen, Weeks 5-6; n=63, 76	100 percentage of participants	97.4 percentage of participants	—
Percentage of Participants Requiring Additional FLS Management Regimen to Relieve BIIB017-related FLS Used additional regimen, first 8 weeks; n=78, 85	6.4 percentage of participants	15.3 percentage of participants	—
Percentage of Participants Requiring Additional FLS Management Regimen to Relieve BIIB017-related FLS No additional regimen, first 8 weeks; n=78, 85	93.6 percentage of participants	84.7 percentage of participants	—
Percentage of Participants Requiring Additional FLS Management Regimen to Relieve BIIB017-related FLS Used additional regimen, Weeks 0-2; n=57, 73	1.8 percentage of participants	11 percentage of participants	—
Percentage of Participants Requiring Additional FLS Management Regimen to Relieve BIIB017-related FLS No additional regimen, Weeks 0-2; n=57, 73	98.2 percentage of participants	89 percentage of participants	—
Percentage of Participants Requiring Additional FLS Management Regimen to Relieve BIIB017-related FLS Used additional regimen, Weeks 3-4; n=61, 77	6.6 percentage of participants	5.2 percentage of participants	—
Percentage of Participants Requiring Additional FLS Management Regimen to Relieve BIIB017-related FLS No additional regimen, Weeks 3-4; n=61, 77	93.4 percentage of participants	94.8 percentage of participants	—
Percentage of Participants Requiring Additional FLS Management Regimen to Relieve BIIB017-related FLS Used additional regimen, Weeks 7-8; n=52, 74	1.9 percentage of participants	4.1 percentage of participants	—
Percentage of Participants Requiring Additional FLS Management Regimen to Relieve BIIB017-related FLS No additional regimen, Weeks 7-8; n=52, 74	98.1 percentage of participants	95.9 percentage of participants	—

SECONDARY outcome

Timeframe: 4-week run-in period, Weeks 4, 12, 24, 36, 48 (or Early Termination)

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment and had efficacy data in both the 4-week run-in period and the post-baseline treatment period; n=number of participants assessed at the given timepoint.

The TSQM assessed participants' global satisfaction with treatment and captured information on treatment side effects, effectiveness, and convenience. Changes from the 4-week run-in period to each visit using transformed scores between 0 and 100 for effectiveness (with higher scores indicating greater satisfaction) are presented. 4WRI=4-week run-in.

Outcome measures

Outcome measures
Measure	Overall Population n=194 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Mean Change From 4-Week Run-In Period at Each Visit for Treatment Satisfaction Questionnaire for Medication (TSQM), Effectiveness Scale Factor: Overall Population Change at Week 12; n=175	-1.274 units on a scale Standard Deviation 30.682	—	—
Mean Change From 4-Week Run-In Period at Each Visit for Treatment Satisfaction Questionnaire for Medication (TSQM), Effectiveness Scale Factor: Overall Population Change at Week 24; n=167	0.341 units on a scale Standard Deviation 27.401	—	—
Mean Change From 4-Week Run-In Period at Each Visit for Treatment Satisfaction Questionnaire for Medication (TSQM), Effectiveness Scale Factor: Overall Population Change at Week 48; n=153	2.863 units on a scale Standard Deviation 29.172	—	—
Mean Change From 4-Week Run-In Period at Each Visit for Treatment Satisfaction Questionnaire for Medication (TSQM), Effectiveness Scale Factor: Overall Population Change at Early Termination; n=26	-17.308 units on a scale Standard Deviation 34.534	—	—
Mean Change From 4-Week Run-In Period at Each Visit for Treatment Satisfaction Questionnaire for Medication (TSQM), Effectiveness Scale Factor: Overall Population Effectiveness at 4WRI; n=194	73.871 units on a scale Standard Deviation 20.131	—	—
Mean Change From 4-Week Run-In Period at Each Visit for Treatment Satisfaction Questionnaire for Medication (TSQM), Effectiveness Scale Factor: Overall Population Change at Week 4; n=185	-2.589 units on a scale Standard Deviation 28.139	—	—
Mean Change From 4-Week Run-In Period at Each Visit for Treatment Satisfaction Questionnaire for Medication (TSQM), Effectiveness Scale Factor: Overall Population Change at Week 36; n =162	1.864 units on a scale Standard Deviation 29.175	—	—

SECONDARY outcome

Timeframe: 4-week run-in period, Weeks 4, 12, 24, 36, 48 (or Early Termination)

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment and had efficacy data in both the 4-week run-in period and the post-baseline treatment period; n=number of participants assessed at the given timepoint.

The TSQM assessed participants' global satisfaction with treatment and captured information on treatment side effects, effectiveness, and convenience. Changes from the 4-week run-in period to each visit using transformed scores between 0 and 100 for side effects (with higher scores indicating greater satisfaction) are presented. 4WRI=4-week run-in.

Outcome measures

Outcome measures
Measure	Overall Population n=194 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Side-Effects Scale Factor: Overall Population Side Effects at 4WRI; n=194	85.17 units on a scale Standard Deviation 18.136	—	—
Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Side-Effects Scale Factor: Overall Population Change at Week 4; n=185	6.065 units on a scale Standard Deviation 21.243	—	—
Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Side-Effects Scale Factor: Overall Population Change at Week 12; n=175	5.109 units on a scale Standard Deviation 19.67	—	—
Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Side-Effects Scale Factor: Overall Population Change at Week 24; n=167	2.958 units on a scale Standard Deviation 18.131	—	—
Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Side-Effects Scale Factor: Overall Population Change at Week 36; n=162	3.37 units on a scale Standard Deviation 18.207	—	—
Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Side-Effects Scale Factor: Overall Population Change at Week 48; n=153	1.418 units on a scale Standard Deviation 20.922	—	—
Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Side-Effects Scale Factor: Overall Population Change at Early Termination; n=26	-18.731 units on a scale Standard Deviation 31.776	—	—

SECONDARY outcome

Timeframe: 4-week run-in period, Weeks 4, 12, 24, 36, 48 (or Early Termination)

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment and had efficacy data in both the 4-week run-in period and the post-baseline treatment period; n=number of participants assessed at the given timepoint.

The TSQM assessed participants' global satisfaction with treatment and captured information on treatment side effects, effectiveness, and convenience. Changes from the 4-week run-in period to each visit using transformed scores between 0 and 100 for convenience (with higher scores indicating greater satisfaction) are presented. 4WRI=4-week run-in.

Outcome measures

Outcome measures
Measure	Overall Population n=194 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Convenience Scale Factor: Overall Population Change at Week 24; n=167	18.419 units on a scale Standard Deviation 20.804	—	—
Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Convenience Scale Factor: Overall Population Convenience at 4WRI; n=194	66.665 units on a scale Standard Deviation 16.588	—	—
Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Convenience Scale Factor: Overall Population Change at Week 4; n=185	18.703 units on a scale Standard Deviation 21.864	—	—
Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Convenience Scale Factor: Overall Population Change at Week 12; n=175	18.12 units on a scale Standard Deviation 20.588	—	—
Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Convenience Scale Factor: Overall Population Change at Week 36; n =162	18.704 units on a scale Standard Deviation 21.258	—	—
Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Convenience Scale Factor: Overall Population Change at Week 48; n=153	19.588 units on a scale Standard Deviation 20.912	—	—
Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Convenience Scale Factor: Overall Population Change at Early Termination; n=26	7.808 units on a scale Standard Deviation 28.788	—	—

SECONDARY outcome

Timeframe: 4-week run-in period, Weeks 4, 12, 24, 36, 48 (or Early Termination)

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment and had efficacy data in both the 4-week run-in period and the post-baseline treatment period; n=number of participants assessed at the given timepoint.

The TSQM assessed participants' global satisfaction with treatment and captured information on treatment side effects, effectiveness, and convenience. Changes from the 4-week run-in period to each visit using transformed scores between 0 and 100 for global satisfaction (with higher scores indicating greater satisfaction) are presented. 4WRI=4-week run-in.

Outcome measures

Outcome measures
Measure	Overall Population n=194 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Global Satisfaction Scale Factor: Overall Population Global Satisfaction at 4WRI; n=194	75.985 units on a scale Standard Deviation 15.137	—	—
Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Global Satisfaction Scale Factor: Overall Population Change at Week 4; n=185	6.789 units on a scale Standard Deviation 19.8	—	—
Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Global Satisfaction Scale Factor: Overall Population Change at Week 12; n=175	7.354 units on a scale Standard Deviation 20.296	—	—
Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Global Satisfaction Scale Factor: Overall Population Change at Week 24; n=167	7.575 units on a scale Standard Deviation 19.91	—	—
Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Global Satisfaction Scale Factor: Overall Population Change at Week 36; n =162	9.179 units on a scale Standard Deviation 19.215	—	—
Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Global Satisfaction Scale Factor: Overall Population Change at Week 48; n=153	8.556 units on a scale Standard Deviation 23.389	—	—
Mean Change From 4-Week Run-In Period at Each Visit for TSQM, Global Satisfaction Scale Factor: Overall Population Change at Early Termination; n=26	-38.538 units on a scale Standard Deviation 26.224	—	—

SECONDARY outcome

Timeframe: 4-week run-in period, Week 4

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment and had efficacy data in both the 4-week run-in period and the post-baseline treatment period; n=number of participants assessed at the given timepoint.

The TSQM assessed participants' global satisfaction with treatment and captured information on treatment side effects, effectiveness, and convenience. Changes from the 4-week run-in period to Week 4 using transformed scores between 0 and 100 for effectiveness (with higher scores indicating greater satisfaction) are presented. This secondary endpoint was targeted for Week 4 only. 4WRI=4-week run-in.

Outcome measures

Outcome measures
Measure	Overall Population n=100 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen n=94 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Effectiveness Scale Factor: Between FLS Management Arms Effectiveness at 4WRI; n=100, 94	75.16 units on a scale Standard Deviation 19.431	72.5 units on a scale Standard Deviation 20.866	—
Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Effectiveness Scale Factor: Between FLS Management Arms Change at Week 4; n=95, 90	0.979 units on a scale Standard Deviation 24.793	-6.356 units on a scale Standard Deviation 30.982	—

SECONDARY outcome

Timeframe: 4-week run-in period, Week 4

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment and had efficacy data in both the 4-week run-in period and the post-baseline treatment period; n=number of participants assessed at the given timepoint.

The TSQM assessed participants' global satisfaction with treatment and captured information on treatment side effects, effectiveness, and convenience. Changes from the 4-week run-in period to Week 4 using transformed scores between 0 and 100 for side effects (with higher scores indicating greater satisfaction) are presented. This secondary endpoint was targeted for Week 4 only. 4WRI=4-week run-in.

Outcome measures

Outcome measures
Measure	Overall Population n=100 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen n=94 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Side Effects Scale Factor: Between FLS Management Arms Side Effects at 4WRI; n=100, 94	83.78 units on a scale Standard Deviation 20.074	86.649 units on a scale Standard Deviation 15.789	—
Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Side Effects Scale Factor: Between FLS Management Arms Change at Week 4; n=95, 90	8.579 units on a scale Standard Deviation 23.576	3.411 units on a scale Standard Deviation 18.222	—

SECONDARY outcome

Timeframe: 4-week run-in period, Week 4

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment and had efficacy data in both the 4-week run-in period and the post-baseline treatment period; n=number of participants assessed at the given timepoint.

The TSQM assessed participants' global satisfaction with treatment and captured information on treatment side effects, effectiveness, and convenience. Changes from the 4-week run-in period to Week 4 using transformed scores between 0 and 100 for convenience (with higher scores indicating greater satisfaction) are presented. This secondary endpoint was targeted for Week 4 only. 4WRI=4-week run-in.

Outcome measures

Outcome measures
Measure	Overall Population n=100 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen n=94 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Convenience Scale Factor: Between FLS Management Arms Change at Week 4; n=95, 90	19.768 units on a scale Standard Deviation 22.403	17.578 units on a scale Standard Deviation 21.347	—
Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Convenience Scale Factor: Between FLS Management Arms Convenience at 4WRI; n=100, 94	65.94 units on a scale Standard Deviation 15.878	67.436 units on a scale Standard Deviation 17.365	—

SECONDARY outcome

Timeframe: 4-week run-in period, Week 4

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment and had efficacy data in both the 4-week run-in period and the post-baseline treatment period; n=number of participants assessed at the given timepoint.

The TSQM assessed participants' global satisfaction with treatment and captured information on treatment side effects, effectiveness, and convenience. Changes from the 4-week run-in period to Week 4 using transformed scores between 0 and 100 for global satisfaction (with higher scores indicating greater satisfaction) are presented. This secondary endpoint was targeted for Week 4 only. 4WRI=4-week run-in.

Outcome measures

Outcome measures
Measure	Overall Population n=100 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen n=94 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Global Satisfaction Scale Factor: Between FLS Management Arms Global Satisfaction at 4WRI; n=100, 94	75.86 units on a scale Standard Deviation 14.001	76.117 units on a scale Standard Deviation 16.334	—
Mean Change From 4-Week Run-In Period at Week 4 for TSQM, Global Satisfaction Scale Factor: Between FLS Management Arms Change at Week 4; n=95, 90	8.663 units on a scale Standard Deviation 16.633	4.811 units on a scale Standard Deviation 22.596	—

SECONDARY outcome

Timeframe: Week -4 (screening), Week 12, Week 24, Week 36, Week 48, Early Termination

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment, had efficacy data in both the 4-week run-in period and the post-baseline treatment period, and were employed; n=number of participants assessed at the given timepoint.

Categorical questions in the Absenteeism Questionnaire asked participants to report the number of usual work days per week, the number of days missed in 2 weeks from multiple sclerosis (MS) symptoms, and the number of days missed in 2 weeks from MS treatment. This secondary endpoint was targeted to analyze the Overall Population only. 4WRI=4-week run-in.

Outcome measures

Outcome measures
Measure	Overall Population n=123 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Usual Work Days Per Week: Overall Population Days in 4WRI; n=123	4.691 days Standard Deviation 1.033	—	—
Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Usual Work Days Per Week: Overall Population Change at Week 12; n=106	-0.019 days Standard Deviation 0.436	—	—
Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Usual Work Days Per Week: Overall Population Change at Week 24; n=99	-0.081 days Standard Deviation 0.566	—	—
Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Usual Work Days Per Week: Overall Population Change at Week 36; n=96	-0.052 days Standard Deviation 0.773	—	—
Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Usual Work Days Per Week: Overall Population Change at Week 48; n=95	0.032 days Standard Deviation 0.573	—	—
Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Usual Work Days Per Week: Overall Population Change at Early Termination; n=15	0.2 days Standard Deviation 0.862	—	—

SECONDARY outcome

Timeframe: Week -4 (screening), Week 12, Week 24, Week 36, Week 48, Early Termination

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment, had efficacy data in both the 4-week run-in period and the post-baseline treatment period, and were employed; n=number of participants assessed at the given timepoint.

Categorical questions in the Absenteeism Questionnaire asked participants to report the number of usual work days per week, the number of days missed in 2 weeks from MS symptoms, and the number of days missed in 2 weeks from MS treatment. This secondary endpoint was targeted to analyze the Overall Population only. 4WRI=4-week run-in.

Outcome measures

Outcome measures
Measure	Overall Population n=123 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Days Missed in 2 Weeks From MS Symptoms: Overall Population Change at Week 36; n=96	0 days Standard Deviation 0.205	—	—
Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Days Missed in 2 Weeks From MS Symptoms: Overall Population Change at Week 48; n =95	0.137 days Standard Deviation 1.078	—	—
Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Days Missed in 2 Weeks From MS Symptoms: Overall Population Change at Early Termination; n=15	0 days Standard Deviation 0	—	—
Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Days Missed in 2 Weeks From MS Symptoms: Overall Population Days in 4WRI; n=123	0.016 days Standard Deviation 0.127	—	—
Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Days Missed in 2 Weeks From MS Symptoms: Overall Population Change at Week 12; n=106	0.057 days Standard Deviation 0.513	—	—
Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Days Missed in 2 Weeks From MS Symptoms: Overall Population Change at Week 24; n=99	0.061 days Standard Deviation 0.373	—	—

SECONDARY outcome

Timeframe: Week -4 (screening), Week 12, Week 24, Week 36, Week 48, Early Termination

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment, had efficacy data in both the 4-week run-in period and the post-baseline treatment period, and were employed; n=number of participants assessed at the given timepoint.

Categorical questions in the Absenteeism Questionnaire asked participants to report the number of usual work days per week, the number of days missed in 2 weeks from MS symptoms, and the number of days missed in 2 weeks from MS treatment. This secondary endpoint was targeted to analyze the Overall Population only. 4WRI=4-week run-in.

Outcome measures

Outcome measures
Measure	Overall Population n=123 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Days Missed in 2 Weeks From MS Treatment: Overall Population Days in 4WRI; n=123	0.016 days Standard Deviation 0.127	—	—
Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Days Missed in 2 Weeks From MS Treatment: Overall Population Change at Week 12; n=106	0.019 days Standard Deviation 0.275	—	—
Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Days Missed in 2 Weeks From MS Treatment: Overall Population Change at Week 24; n=99	0.02 days Standard Deviation 0.319	—	—
Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Days Missed in 2 Weeks From MS Treatment: Overall Population Change at Week 36; n=96	-0.021 days Standard Deviation 0.144	—	—
Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Days Missed in 2 Weeks From MS Treatment: Overall Population Change at Week 48; n =95	0.126 days Standard Deviation 1.074	—	—
Mean Change From Screening at Each Visit in Absenteeism Questionnaire, Days Missed in 2 Weeks From MS Treatment: Overall Population Change at Early Termination; n=15	0.2 days Standard Deviation 0.414	—	—

SECONDARY outcome

Timeframe: Day 1 (Baseline, pre-dose), Week 12, Week 48, Early Termination

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment and had efficacy data in both the 4-week run-in period and the post-baseline treatment period; n=number of participants assessed at the given timepoint.

Subjects rated their perceived walking disability on a scale of 0 to 8 using the PDDS, with higher scores indicating more severe disability. This secondary endpoint was targeted to analyze the Overall Population only.

Outcome measures

Outcome measures
Measure	Overall Population n=194 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Change From Baseline Visit (Day 1) to Week 48 in Walking Disability Status as Measured by Patient Determined Disease Steps (PDDS): Overall Population Baseline; n=194	0.83 units on a scale Standard Deviation 1.258	—	—
Change From Baseline Visit (Day 1) to Week 48 in Walking Disability Status as Measured by Patient Determined Disease Steps (PDDS): Overall Population Change at Week 12; n=174	0.029 units on a scale Standard Deviation 0.836	—	—
Change From Baseline Visit (Day 1) to Week 48 in Walking Disability Status as Measured by Patient Determined Disease Steps (PDDS): Overall Population Change at Week 48; n=153	0.15 units on a scale Standard Deviation 0.857	—	—
Change From Baseline Visit (Day 1) to Week 48 in Walking Disability Status as Measured by Patient Determined Disease Steps (PDDS): Overall Population Change Early Termination; n=26	0.346 units on a scale Standard Deviation 1.093	—	—

SECONDARY outcome

Timeframe: Day 1 to Week 52

Population: Safety population: all participants who received at least 1 injection of study treatment.

An AE was any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. An SAE was any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigator, placed the subject at immediate risk of death (a life-threatening event); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, could jeopardize the subject or could require intervention to prevent one of the other outcomes listed in the definition above. ISR=injection site reactions.

Outcome measures

Outcome measures
Measure	Overall Population n=103 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen n=98 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Summary of Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Any event	93 participants	90 participants	—
Summary of Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Serious event	4 participants	6 participants	—
Summary of Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Moderate or severe event	54 participants	60 participants	—
Summary of Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Severe event	7 participants	12 participants	—
Summary of Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Related event	80 participants	71 participants	—
Summary of Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Discontinuations due to AEs	14 participants	13 participants	—
Summary of Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Treatment discontinuation due to FLS event	3 participants	2 participants	—
Summary of Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Treatment discontinuation due to ISR events	5 participants	3 participants	—
Summary of Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Study discontinuation due to an event	13 participants	13 participants	—

SECONDARY outcome

Timeframe: Weeks -4 to -1 (Screening), Weeks 45-48 (last 4 weeks of study)

Population: Efficacy population: randomized participants who received at least 1 dose of study treatment, had efficacy data in both the 4-week run-in period and the post-baseline treatment period, and had FLS; n=number of participants assessed at the given timepoint.

Average duration of FLS for the last 4 weeks (L4W) is defined as the mean duration of last 4 weeks. Duration of FLS for a treatment is defined as the sum of hours from the treatment to 48 hours with a FLS-S score \> 0. The total FLS-S is the sum of all 4 symptom scores (muscle aches, chills, fatigue and fever), each rated from 0 (absent) to 3 (severe), with a range of 0-12 with 0 indicating no FLS and 12 indicating severe FLS. If a FLS is \> 0 at an evaluation time, 6 hours were counted as the duration assuming the event started from previous evaluation time. 4WRI=4-week run-in.

Outcome measures

Outcome measures
Measure	Overall Population n=88 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen n=86 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population n=174 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Summary of Average Duration of FLS Within the Last 4 Weeks of the BIIB017 Treatment Period Compared With the Duration of FLS in the 4-Week Run-In Period Average duration in 4WRI; n=88, 86, 174	16.067 hours Standard Deviation 8.277	14.915 hours Standard Deviation 7.637	15.497 hours Standard Deviation 7.965
Summary of Average Duration of FLS Within the Last 4 Weeks of the BIIB017 Treatment Period Compared With the Duration of FLS in the 4-Week Run-In Period Change from 4WRI to L4W; n=80, 77, 157	2.612 hours Standard Deviation 8.067	0.943 hours Standard Deviation 6.738	1.793 hours Standard Deviation 7.468
Summary of Average Duration of FLS Within the Last 4 Weeks of the BIIB017 Treatment Period Compared With the Duration of FLS in the 4-Week Run-In Period Average duration in L4W; n=87, 83, 170	18.057 hours Standard Deviation 9.06	15.892 hours Standard Deviation 8.073	17 hours Standard Deviation 8.635

SECONDARY outcome

Timeframe: Baseline (BL; Day 1), Week 12, Week 24, Week 36, Week 48 or early withdrawal (EW)

Population: Safety population: participants who received at least 1 injection of study treatment and had an assessment; n=number of participants with an assessment at given timepoint.

The number of participants who tested positive for IFN β-1a binding antibodies (BAbs). Value was coded as 'positive' if observed value \> 0 or coded as 'negative' if observed value \< 0. This secondary endpoint was targeted to analyze the Overall Population only.

Outcome measures

Outcome measures
Measure	Overall Population n=199 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Antibody Data in the Overall Population: IFN β-1a Antibody Screening Week 12: Negative; n=183	157 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Antibody Screening Week 24: Positive; n=171	22 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Antibody Screening Baseline: Positive; n=199	22 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Antibody Screening Baseline: Negative; n=199	177 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Antibody Screening Any post-baseline visit: Positive; n=198	35 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Antibody Screening Any post-baseline visit: Negative; n=198	178 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Antibody Screening Week 12: Positive; n=183	26 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Antibody Screening Week 24: Negative; n=171	149 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Antibody Screening Week 36: Positive; n=167	18 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Antibody Screening Week 36: Negative; n=167	149 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Antibody Screening Week 48/EW: Positive; n=193	25 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Antibody Screening Week 48/EW: Negative; n=193	168 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Antibody Screening Negative at BL with ≥ 1 positive post-BL; n=174	13 participants	—	—

SECONDARY outcome

Timeframe: Baseline (BL; Day 1), Week 12, Week 24, Week 36, Week 48 or early withdrawal (EW)

Population: Safety population: participants who received at least 1 injection of study treatment and had an assessment; n=number of participants with an assessment at given timepoint.

The number of participants who tested positive or negative for IFN β-1a anti-PEG antibodies. Value was coded as 'positive' if observed value \> 0 or coded as 'negative' if observed value \< 0. This secondary endpoint was targeted to analyze the Overall Population only.

Outcome measures

Outcome measures
Measure	Overall Population n=201 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Antibody Data in the Overall Population: IFN β-1a Anti-Pegylated (PEG) Antibody Testing Week 24: Positive; n=173	3 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Anti-Pegylated (PEG) Antibody Testing Week 24: Negative; n=173	170 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Anti-Pegylated (PEG) Antibody Testing Baseline: Positive; n=201	7 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Anti-Pegylated (PEG) Antibody Testing Baseline: Negative; n=201	194 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Anti-Pegylated (PEG) Antibody Testing Any post-baseline visit: Positive; n=198	8 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Anti-Pegylated (PEG) Antibody Testing Any post-baseline visit: Negative; n=198	196 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Anti-Pegylated (PEG) Antibody Testing Week 12: Positive; n=182	6 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Anti-Pegylated (PEG) Antibody Testing Week 12: Negative; n=182	176 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Anti-Pegylated (PEG) Antibody Testing Week 36: Positive; n=168	1 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Anti-Pegylated (PEG) Antibody Testing Week 36: Negative; n=168	167 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Anti-Pegylated (PEG) Antibody Testing Week 48/EW: Positive; n=193	3 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Anti-Pegylated (PEG) Antibody Testing Week 48/EW: Negative; n=193	190 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Anti-Pegylated (PEG) Antibody Testing Negative at BL with ≥ 1 positive post-BL; n=192	4 participants	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1), Week 12, Week 24, Week 36, Week 48 or early withdrawal (EW)

Population: Safety population: participants who received at least 1 injection of study treatment and had an assessment; n=number of participants with an assessment at given timepoint.

The number of participants who tested positive for IFN β-1a Nabs. Value was coded as 'positive' if observed value \> 0 or coded as 'negative' if observed value \< 0. This secondary endpoint was targeted to analyze the Overall Population only.

Outcome measures

Outcome measures
Measure	Overall Population n=201 Participants Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	BIIB017 Plus Naproxen Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently.	Overall Population Following a 4-week run-in period (starting 1 day after the Screening Visit) in which participants administered non-pegylated IFN therapy, participants received BIIB017 at an initial dose of 63 μg followed by 94 μg dose at Week 2 and 125 μg every 2 weeks from Week 4 to Week 46, plus: * current FLS management regimen as determined by the clinician; or * 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Antibody Data in the Overall Population: IFN β-1a Neutralizing Antibodies (Nabs) Testing Baseline: Positive; n=22	14 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Neutralizing Antibodies (Nabs) Testing Baseline: Negative; n=22	8 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Neutralizing Antibodies (Nabs) Testing Any post-baseline visit: Positive; n=35	17 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Neutralizing Antibodies (Nabs) Testing Any post-baseline visit: Negative; n=35	20 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Neutralizing Antibodies (Nabs) Testing Week 12: Positive; n=26	15 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Neutralizing Antibodies (Nabs) Testing Week 12: Negative; n=26	11 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Neutralizing Antibodies (Nabs) Testing Week 24: Positive; n=22	11 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Neutralizing Antibodies (Nabs) Testing Week 24: Negative; n=22	11 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Neutralizing Antibodies (Nabs) Testing Week 36: Positive; n=18	11 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Neutralizing Antibodies (Nabs) Testing Week 36: Negative; n=18	7 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Neutralizing Antibodies (Nabs) Testing Week 48/EW: Positive; n=25	12 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Neutralizing Antibodies (Nabs) Testing Week 48/EW: Negative; n=25	13 participants	—	—
Antibody Data in the Overall Population: IFN β-1a Neutralizing Antibodies (Nabs) Testing Negative at BL with ≥ 1 positive post-BL; n=7	1 participants	—	—

Adverse Events

BIIB017 Plus Current FLS Therapy

Serious events: 4 serious events

Other events: 92 other events

Deaths: 0 deaths

BIIB017 Plus Naproxen

Serious events: 6 serious events

Other events: 90 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	BIIB017 Plus Current FLS Therapy n=103 participants at risk BIIB017 initial dose of 63 μg followed by 94 μg dose at week 2 and 125 μg every 2 weeks from week 4 to week 46, plus current FLS management regimen as determined by the clinician	BIIB017 Plus Naproxen n=98 participants at risk BIIB017 initial dose of 63 μg followed by 94 μg dose at week 2 and 125 μg every 2 weeks from week 4 to week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Appendix cancer	0.00% 0/103 • Day 1 to Week 52	1.0% 1/98 • Day 1 to Week 52
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/103 • Day 1 to Week 52	1.0% 1/98 • Day 1 to Week 52
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/103 • Day 1 to Week 52	1.0% 1/98 • Day 1 to Week 52
Gastrointestinal disorders Gastritis	0.97% 1/103 • Day 1 to Week 52	0.00% 0/98 • Day 1 to Week 52
Gastrointestinal disorders Gastrointestinal disorder	0.97% 1/103 • Day 1 to Week 52	0.00% 0/98 • Day 1 to Week 52
Infections and infestations Abscess limb	0.97% 1/103 • Day 1 to Week 52	0.00% 0/98 • Day 1 to Week 52
Infections and infestations Influenza	0.97% 1/103 • Day 1 to Week 52	0.00% 0/98 • Day 1 to Week 52
Infections and infestations Pneumonia	0.97% 1/103 • Day 1 to Week 52	0.00% 0/98 • Day 1 to Week 52
Infections and infestations Sepsis	0.97% 1/103 • Day 1 to Week 52	0.00% 0/98 • Day 1 to Week 52
Infections and infestations Urinary tract infection	0.97% 1/103 • Day 1 to Week 52	0.00% 0/98 • Day 1 to Week 52
Cardiac disorders Acute myocardial infarction	0.00% 0/103 • Day 1 to Week 52	1.0% 1/98 • Day 1 to Week 52
Cardiac disorders Arteriospasm coronary	0.00% 0/103 • Day 1 to Week 52	1.0% 1/98 • Day 1 to Week 52
Endocrine disorders Hyperthyroidism	0.00% 0/103 • Day 1 to Week 52	1.0% 1/98 • Day 1 to Week 52
Injury, poisoning and procedural complications Fall	0.00% 0/103 • Day 1 to Week 52	1.0% 1/98 • Day 1 to Week 52
Injury, poisoning and procedural complications Hip fracture	0.00% 0/103 • Day 1 to Week 52	1.0% 1/98 • Day 1 to Week 52
Nervous system disorders Multiple sclerosis relapse	0.00% 0/103 • Day 1 to Week 52	1.0% 1/98 • Day 1 to Week 52
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.97% 1/103 • Day 1 to Week 52	0.00% 0/98 • Day 1 to Week 52

Other adverse events

Other adverse events
Measure	BIIB017 Plus Current FLS Therapy n=103 participants at risk BIIB017 initial dose of 63 μg followed by 94 μg dose at week 2 and 125 μg every 2 weeks from week 4 to week 46, plus current FLS management regimen as determined by the clinician	BIIB017 Plus Naproxen n=98 participants at risk BIIB017 initial dose of 63 μg followed by 94 μg dose at week 2 and 125 μg every 2 weeks from week 4 to week 46, plus 500 mg naproxen administered twice daily up to 24 hours prior to BIIB017 treatment and continuing for 48 hours following the BIIB017 injection for the first 8 weeks of treatment, and as recommended by the treating physician subsequently
General disorders Injection site erythema	44.7% 46/103 • Day 1 to Week 52	34.7% 34/98 • Day 1 to Week 52
General disorders Injection site reaction	22.3% 23/103 • Day 1 to Week 52	21.4% 21/98 • Day 1 to Week 52
General disorders Influenza like illness	10.7% 11/103 • Day 1 to Week 52	13.3% 13/98 • Day 1 to Week 52
General disorders Injection site pruritus	11.7% 12/103 • Day 1 to Week 52	7.1% 7/98 • Day 1 to Week 52
General disorders Injection site pain	7.8% 8/103 • Day 1 to Week 52	3.1% 3/98 • Day 1 to Week 52
General disorders Injection site bruising	3.9% 4/103 • Day 1 to Week 52	6.1% 6/98 • Day 1 to Week 52
General disorders Fatigue	1.9% 2/103 • Day 1 to Week 52	6.1% 6/98 • Day 1 to Week 52
General disorders Pain	1.9% 2/103 • Day 1 to Week 52	6.1% 6/98 • Day 1 to Week 52
General disorders Chills	5.8% 6/103 • Day 1 to Week 52	1.0% 1/98 • Day 1 to Week 52
Infections and infestations Urinary tract infection	7.8% 8/103 • Day 1 to Week 52	10.2% 10/98 • Day 1 to Week 52
Infections and infestations Upper respiratory tract infection	4.9% 5/103 • Day 1 to Week 52	10.2% 10/98 • Day 1 to Week 52
Infections and infestations Sinusitis	9.7% 10/103 • Day 1 to Week 52	4.1% 4/98 • Day 1 to Week 52
Nervous system disorders Headache	8.7% 9/103 • Day 1 to Week 52	6.1% 6/98 • Day 1 to Week 52
Nervous system disorders Multiple sclerosis relapse	0.97% 1/103 • Day 1 to Week 52	7.1% 7/98 • Day 1 to Week 52
Musculoskeletal and connective tissue disorders Arthralgia	1.9% 2/103 • Day 1 to Week 52	7.1% 7/98 • Day 1 to Week 52
Musculoskeletal and connective tissue disorders Back pain	6.8% 7/103 • Day 1 to Week 52	1.0% 1/98 • Day 1 to Week 52
Gastrointestinal disorders Constipation	1.9% 2/103 • Day 1 to Week 52	6.1% 6/98 • Day 1 to Week 52
Psychiatric disorders Depression	2.9% 3/103 • Day 1 to Week 52	6.1% 6/98 • Day 1 to Week 52

Additional Information

Biogen Study Medical Director

Biogen

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
Publication restrictions are in place

Restriction type: OTHER