A Study of Ixekizumab (LY2439821) in Participants With Nonradiographic Axial Spondyloarthritis (COAST-X)

• ClinicalTrials.gov Identifier: NCT02757352
• Recruitment Status: Completed
• First Posted: May 2, 2016
• Results First Posted: March 13, 2020
• Last Update Posted: March 13, 2020
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Axial Spondyloarthritis
• Interventions: Drug: Ixekizumab; Drug: Placebo
• Enrollment: 303

Participant Flow

Recruitment Details	This study has 3 periods: Period 1 - Screening; Period 2 - A Double-Blind Treatment Period (Weeks 0 Up to 52); (Inadequate Responders [IR] Week 16-52) followed by a Follow-Up Period (Up to 24 Weeks after last visit)
Pre-assignment Details	Participants who completed study were eligible to enroll into a long-term study (Study I1F-MC-RHBY [RHBY]) for up to 2 additional years. Participants that do not enroll into study RHBY will complete the Post-Treatment Follow-Up Period.

Arm/Group Title	Placebo Double-Blind Period	Ixekizumab 80 mg Q4W (IxeQ4W) Double-Blind Period	Ixekizumab 80 mg Q2W (IxeQ2W) Double-Blind Period	PBO IR/Ixe80Q2W-Open Label	Ixekizumab 80 mg Q4W IR (Ixe80Q4WIR)/Ixe80Q2W-Open Label	Ixekizumab 80 mg Q2W IR (Ixe80Q2WIR)/Ixe80Q2W-Open Label	Placebo Post Treatment Follow-Up Period	Ixekizumab 80 mg Q4W Post Treatment Follow-Up Period	Ixekizumab 80 mg Q2W Post Treatment Follow-Up Period	Other Biologic Treatment Group
Arm/Group Description	Participants received placebo (PBO) as 2 subcutaneous (SC) injections every two weeks (Q2W) to week 52.	Participants received a starting dose of 80 or 160 milligram (mg) of ixekizumab given subcutaneously (SC) at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC (Q2W) to week 52.	Participants who received placebo in double blind period and were inadequate responders as determined by investigators switched to ixekizumab 80 mg Q2W open label.	Participants who received ixekizumab 80 mg Q4W in double blind period and were inadequate responders as determined by investigators switched to ixekizumab 80 mg Q2W open label.	Participants who received ixekizumab 80 mg Q2W in double blind period and were inadequate responders as determined by investigators continued on the same regimen of ixekizumab 80 mg Q2W open label.	Participants discontinued the study early and entered the post-treatment follow-up period. Participants received placebo immediately prior to entering the post-treatment follow-up period.	Participants discontinued the study early and entered the post-treatment follow-up period. Participants received ixekizumab 80 mg Q4W immediately prior to entering the post-treatment follow-up period.	Participants discontinued the study early and entered the post-treatment follow-up period. Participants received ixekizumab 80 mg Q2W immediately prior to entering the post-treatment follow-up period	Participants who discontinued study treatment and were on other biologic therapy prior to entering follow-up period.
Period Title: Double-Blind Period (Week 0 - Week 16)
Started	105	96	102	0	0	0	0	0	0	0
Received at Least One Dose of Study Drug	104	96	102	0	0	0	0	0	0	0
Completed	97	95	98	0	0	0	0	0	0	0
Not Completed	8	1	4	0	0	0	0	0	0	0
Reason Not Completed
Adverse Event	2	0	1	0	0	0	0	0	0	0
Lost to Follow-up	0	0	1	0	0	0	0	0	0	0
Withdrawal by Subject	6	1	2	0	0	0	0	0	0	0
Period Title: Double-Blind Period (Week 16 - Week 52)
Started	97	95	98	0	0	0	0	0	0	0
Completed	34	52	52	0	0	0	0	0	0	0
Not Completed	63	43	46	0	0	0	0	0	0	0
Reason Not Completed
Adverse Event	0	1	0	0	0	0	0	0	0	0
Lack of Efficacy	0	1	0	0	0	0	0	0	0	0
Withdrawal by Subject	1	1	4	0	0	0	0	0	0	0
Classified as Inadequate Responders (IR)	62	40	42	0	0	0	0	0	0	0
Period Title: IR-Open Label Period (Week 16 - Week 52)
Started	0 [1]	0 [1]	0 [1]	62 [2]	40 [2]	42 [2]	0	0	0	0
Initiated Other Biologic Rescue	0	0	0	2	0	3	0	0	0	0
Completed	0	0	0	55	37	35	0	0	0	0
Not Completed	0	0	0	7	3	7	0	0	0	0
Reason Not Completed
Adverse Event	0	0	0	3	0	1	0	0	0	0
Lack of Efficacy	0	0	0	2	1	4	0	0	0	0
Pregnancy	0	0	0	0	1	0	0	0	0	0
Physician Decision	0	0	0	0	0	1	0	0	0	0
Withdrawal by Subject	0	0	0	2	1	1	0	0	0	0
[1] Participants continued with original assigned treatment without switching to open label ixeQ2W.; [2] IR based on the investigator's opinion switched to ixekizumab open label 80 mg Q2W.
Period Title: Follow-Up Period
Started	0	0	0	0 [1]	0 [1]	0 [1]	3 [1]	5 [1]	28 [1]	5
Completed	0	0	0	0	0	0	2	4	18	2
Not Completed	0	0	0	0	0	0	1	1	10	3
Reason Not Completed
Adverse Event	0	0	0	0	0	0	1	0	2	0
Lost to Follow-up	0	0	0	0	0	0	0	0	1	0
Lack of Efficacy	0	0	0	0	0	0	0	0	1	1
Withdrawal by Subject	0	0	0	0	0	0	0	1	6	2
[1] Participants who completed the study were eligible to enroll in RHBY or enter follow up period.

Baseline Characteristics

Arm/Group Title		Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W	Total
Arm/Group Description		Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.	Total of all reporting groups
Overall Number of Baseline Participants		105	96	102	303
Baseline Analysis Population Description		All randomized participants.
Age, Continuous [1]; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	104 participants	96 participants	102 participants	302 participants
		39.9 (12.36)	40.9 (14.47)	40.0 (12.01)	40.3 (12.92)
		[1] Measure Analysis Population Description: Participants who had evaluable data for age were reported due to 1 participant that did not receive study drug.
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	105 participants	96 participants	102 participants	303 participants
	Female	61	46	53	160
	Male	44	50	49	143
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	105 participants	96 participants	102 participants	303 participants
	Hispanic or Latino	25	24	31	80
	Not Hispanic or Latino	68	57	63	188
	Unknown or Not Reported	12	15	8	35
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	105 participants	96 participants	102 participants	303 participants
	American Indian or Alaska Native	8	2	3	13
	Asian	17	13	11	41
	Native Hawaiian or Other Pacific Islander	0	0	0	0
	Black or African American	0	0	0	0
	White	76	80	83	239
	More than one race	3	1	5	9
	Unknown or Not Reported	1	0	0	1
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
Argentina	Number Analyzed	105 participants	96 participants	102 participants	303 participants
		8	6	9	23
Romania	Number Analyzed	105 participants	96 participants	102 participants	303 participants
		5	1	4	10
United States	Number Analyzed	105 participants	96 participants	102 participants	303 participants
		10	9	9	28
Czechia	Number Analyzed	105 participants	96 participants	102 participants	303 participants
		15	16	13	44
Japan	Number Analyzed	105 participants	96 participants	102 participants	303 participants
		6	5	5	16
Russia	Number Analyzed	105 participants	96 participants	102 participants	303 participants
		12	7	8	27
Canada	Number Analyzed	105 participants	96 participants	102 participants	303 participants
		1	3	2	6
Austria	Number Analyzed	105 participants	96 participants	102 participants	303 participants
		0	1	2	3
South Korea	Number Analyzed	105 participants	96 participants	102 participants	303 participants
		9	7	6	22
Netherlands	Number Analyzed	105 participants	96 participants	102 participants	303 participants
		0	0	1	1
Finland	Number Analyzed	105 participants	96 participants	102 participants	303 participants
		4	3	3	10
Brazil	Number Analyzed	105 participants	96 participants	102 participants	303 participants
		0	1	2	3
Poland	Number Analyzed	105 participants	96 participants	102 participants	303 participants
		19	18	20	57
Mexico	Number Analyzed	105 participants	96 participants	102 participants	303 participants
		14	13	15	42
Germany	Number Analyzed	105 participants	96 participants	102 participants	303 participants
		2	6	3	11

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving an Assessment of Spondyloarthritis International Society 40 (ASAS40) Response
Description	ASAS40 is defined as a greater than or equal to (≥)40% improvement and an absolute improvement from baseline of ≥2 units (ranges 0 to 10) in at least 3 of the 4 domains (Patient Global, Spinal Pain, Function, and Inflammation), without any worsening in the remaining domain. 1) Patient Global: How active was your spondylitis during the last week? score ranges 0 (not active) to 10 (very active). 2) Spinal Pain: How much spinal pain due to Ankylosing spondylitis? score ranges 0 (no pain) to 10 (severe pain). 3) Bath Ankylosing Spondylitis Functional Index: Participant is asked to rate the difficulty associated with 10 individual basic functional activities. Responses were captured using numeric rating scale (NRS) (ranges 0 to 10) with a higher score of worse function. 4) Inflammation based on mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) question 5 and 6 (mean of intensity, duration of stiffness). Score ranges (0 (non) to 10 (very severe).
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants. For inadequate responders who were treated with open label ixekizumab 80 mg Q2W, only data up to the time of initiation of open label of ixekizumab 80 mg Q2W were included. Missing data was imputed using the nonresponder imputation (NRI) method.

Arm/Group Title	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:	Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed	105	96	102
Measure Type: Number; Unit of Measure: percentage of participants
	19.0	35.4	40.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.009
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.36
	Confidence Interval	(2-Sided) 95%; 1.23 to 4.51
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.002
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.78
	Confidence Interval	(2-Sided) 95%; 1.48 to 5.25
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Percentage of Participants Achieving an ASAS40 Response
Description	ASAS40 is defined as a greater than or equal to (≥)40% improvement and an absolute improvement from baseline of ≥2 units (ranges 0 to 10) in at least 3 of the 4 domains (Patient Global, Spinal Pain, Function, and Inflammation), without any worsening in the remaining domain. 1) Patient Global: How active was your spondylitis during the last week? score ranges 0 (not active) to 10 (very active). 2) Spinal Pain: How much spinal pain due to Ankylosing spondylitis? score ranges 0 (no pain) to 10 (severe pain). 3) Bath Ankylosing Spondylitis Functional Index: Participant is asked to rate the difficulty associated with 10 individual basic functional activities. Responses were captured using numeric rating scale (NRS) (ranges 0 to 10) with a higher score of worse function. 4) Inflammation based on mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) question 5 and 6 (mean of intensity, duration of stiffness). Score ranges (0 (non) to 10 (very severe).
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants. For inadequate responders who were treated with open label ixekizumab 80 mg Q2W, only data up to the time of initiation of open label of ixekizumab 80 mg Q2W were included. Missing data was imputed using the nonresponder imputation (NRI) method.

Arm/Group Title	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:	Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed	105	96	102
Measure Type: Number; Unit of Measure: percentage of participants
	13.3	30.2	31.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.004
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.82
	Confidence Interval	(2-Sided) 95%; 1.38 to 5.77
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.004
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.85
	Confidence Interval	(2-Sided) 95%; 1.40 to 5.77
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS)
Description	ASDAS is a composite index to assess disease activity in axial spondyloarthritis (axSpA). ASDAS parameters used with (C-reactive protein [CRP] as acute phase reactant) are: 1) Total back pain 2) Patient global 3) Peripheral pain/swelling, duration of morning stiffness 4) CRP in mg/L: ASDAScrp is calculated with the equation: 0.121 × total back pain + 0.110×patient global + 0.073 × peripheral pain/swelling + 0.058 × duration of morning stiffness + 0.579 × Ln(CRP+1). CRP is in milligram/liter (mg/L), the range of other variables is from 0 to 10. Data from five variables combined to yield a score (0.6361 to no defined upper limit), where higher scores indicated higher disease activity. Ln represents the natural logarithm. Least squares mean (LS Mean) was derived from mixed models repeated measure analysis (MMRM) with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants. For inadequate responders who were treated with open label ixekizumab 80 mg Q2W, only data up to the time of initiation of open label of ixekizumab 80 mg Q2W were included.

Arm/Group Title	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:	Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed	105	96	102
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	-0.58 (0.095)	-1.12 (0.097)	-1.26 (0.095)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.54
	Confidence Interval	(2-Sided) 95%; -0.81 to -0.28
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.136
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.68
	Confidence Interval	(2-Sided) 95%; -0.94 to -0.41
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.134
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS)
Description	ASDAS is a composite index to assess disease activity in axSpA. ASDAS parameters used (with CRP as acute phase reactant) are: 1 )Total back pain 2) Patient global 3) Peripheral pain/swelling 4) Duration of morning stiffness 5) CRP in mg/L: ASDAScrp is calculated with the following equation: 0.121 × total back pain + 0.110 × patient global + 0.073 × peripheral pain/swelling + 0.058 × duration of morning stiffness + 0.579 × Ln(CRP+1). CRP is in milligram/liter (mg/L), the range of other variables is from 0 to 10. Data from five variables combined to yield a score (0.6361 to no defined upper limit), where higher scores indicated higher disease activity. Ln represents the natural logarithm. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants. For inadequate responders who were treated with open label ixekizumab 80 mg Q2W, only data up to the time of initiation of open label of ixekizumab 80 mg Q2W were included.

Arm/Group Title	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:	Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed	105	96	102
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	-0.78 (0.136)	-1.39 (0.116)	-1.47 (0.116)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.61
	Confidence Interval	(2-Sided) 95%; -0.96 to -0.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.179
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.69
	Confidence Interval	(2-Sided) 95%; -1.05 to -0.34
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.178
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Number of Participants Without Clinically Meaningful Changes in Background Therapy
Description	Number of participants without changes in background therapy while on originally randomized treatment.
Time Frame	Baseline through Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants. Additional analysis not performed due to small number of participants with changes in background therapy and complete overlap with switch to open-label ixekizumab.

Arm/Group Title	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:	Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed	105	96	102
Measure Type: Count of Participants; Unit of Measure: Participants
	98	90	100

6. Secondary Outcome

Title	Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score
Description	The SF-36 is a 36-item patient-administered measure designed to be a short, multipurpose assessment of health in the areas of physical functioning, role - physical, role - emotional, bodily pain, vitality, social functioning, mental health, and general health. The Physical Component Summary score ranges from 0 to 100; higher scores indicate better levels of function and/or better health. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants. For inadequate responders who were treated with open label ixekizumab 80 mg Q2W, only data up to the time of initiation of open label of ixekizumab 80 mg Q2W were included.

Arm/Group Title	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:	Participants received placebo as 2 SC injections Q2W to week 52..	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed	105	96	102
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	5.2103 (0.7999)	8.0612 (0.8129)	7.9600 (0.8023)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.013
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.8509
	Confidence Interval	(2-Sided) 95%; 0.6092 to 5.0926
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.1390
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.015
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.7497
	Confidence Interval	(2-Sided) 95%; 0.5299 to 4.9694
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.1278
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score
Description	The medical outcomes study 36-item short-form health survey (SF-36) SF-36 PCS are summarized using the t-scores. The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants. For inadequate responders who were treated with open label ixekizumab 80 mg Q2W, only data up to the time of initiation of open label of ixekizumab 80 mg Q2W were included.

Arm/Group Title	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:	Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed	105	96	102
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	4.7210 (1.2459)	8.9211 (1.0783)	9.3291 (1.0810)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.012
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.2001
	Confidence Interval	(2-Sided) 95%; 0.9525 to 7.4477
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.6467
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.006
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.6081
	Confidence Interval	(2-Sided) 95%; 1.3629 to 7.8533
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.6455
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Percentage of Participants Achieving ASDAS Low Disease Activity
Description	ASDAS is a composite index to assess disease activity in axSpA. ASDAS low disease activity is defined as a score of <2.1. The parameters used for the ASDAS (with CRP as acute phase reactant) are total back pain, patient global, peripheral pain/swelling, duration of morning stiffness and CRP in mg/L. The ASDAScrp is calculated with the following equation: 0.121×total back pain+0.110×patient global+0.073×peripheral pain/swelling+0.058×duration of morning stiffness+0.579×Ln(CRP+1). CRP is in mg/liter, the range of other variables is from 0(normal) to 10(very severe); Ln represents the natural logarithm). Data from five variables combined to yield a score (0.6361 to no defined upper limit), where higher the score worse the disease activity.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants with baseline ASDAS <2.1. For inadequate responders who were treated with open label ixekizumab 80 mg Q2W, only data up to the time of initiation of open label of ixekizumab 80 mg Q2W were included. Missing data was imputed using the NRI method.

Arm/Group Title	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:	Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed	105	94	102
Measure Type: Number; Unit of Measure: percentage of participants
	12.4	27.7	32.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.008
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.73
	Confidence Interval	(2-Sided) 95%; 1.30 to 5.76
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.43
	Confidence Interval	(2-Sided) 95%; 1.66 to 7.08
	Estimation Comments	[Not Specified]

9. Secondary Outcome

Title	Percentage of Participants Achieving ASDAS Low Disease Activity
Description	ASDAS is a composite index to assess disease activity in axSpA. ASDAS low disease activity is defined as a score of <2.1. The parameters used for the ASDAS (with CRP as acute phase reactant) are total back pain, patient global, peripheral pain/swelling, duration of morning stiffness and CRP in mg/L. The ASDAScrp is calculated with the following equation: 0.121×total back pain+0.110×patient global+0.073×peripheral pain/swelling+0.058×duration of morning stiffness+0.579×Ln(CRP+1). CRP is in mg/liter, the range of other variables is from 0(normal) to 10(very severe); Ln represents the natural logarithm). Data from five variables combined to yield a score (0.6361 to no defined upper limit), where higher the score worse the disease activity.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants with baseline ASDAS <2.1. For inadequate responders who were treated with open label ixekizumab 80 mg Q2W, only data up to the time of initiation of open label of ixekizumab 80 mg Q2W were included. Missing data was imputed using the NRI method.

Arm/Group Title	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:	Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed	105	94	102
Measure Type: Number; Unit of Measure: percentage of participants
	8.6	29.8	27.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.58
	Confidence Interval	(2-Sided) 95%; 2.02 to 10.41
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.99
	Confidence Interval	(2-Sided) 95%; 1.76 to 9.05
	Estimation Comments	[Not Specified]

10. Secondary Outcome

Title	Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
Description	The BASDAI is a participant-reported assessment consisting of 6 questions that relate to 5 major symptoms relevant to axial spondyloarthritis (axSpA): 1) Fatigue, 2) Spinal pain, 3) Peripheral arthritis, 4) Enthesitis, 5) Intensity, and 6) Duration of morning stiffness. Participants need to score each item with a score from 0 to 10 (NRS). Total score is obtained from the average of symptom scores ranging 0 (no problem) to 10 (worst problem), with a higher score indicating more severe AS symptom. LS mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants. For inadequate responders who were treated with open label ixekizumab 80 mg Q2W, only data up to the time of initiation of open label of ixekizumab 80 mg Q2W were included.

Arm/Group Title	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:	Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed	105	96	102
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	-1.51 (0.216)	-2.18 (0.220)	-2.52 (0.217)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.031
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Means Square Difference
	Estimated Value	-0.67
	Confidence Interval	(2-Sided) 95%; -1.28 to -0.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.308
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.01
	Confidence Interval	(2-Sided) 95%; -1.61 to -0.41
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.305
	Estimation Comments	[Not Specified]

11. Secondary Outcome

Title	Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
Description	The BASDAI is a participant-reported assessment consisting of 6 questions that relate to 5 major symptoms relevant to axial spondyloarthritis (axSpA): 1) Fatigue, 2) Spinal pain, 3) Peripheral arthritis, 4) Enthesitis, 5) Intensity, and 6) Duration of morning stiffness. Participants need to score each item with a score from 0 to 10 (NRS). Total score is obtained from the average of symptom scores ranging 0 (no problem) to 10 (worst problem), with a higher score indicating more severe AS symptom. LS mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants. For inadequate responders who were treated with open label ixekizumab 80 mg Q2W, only data up to the time of initiation of open label of ixekizumab 80 mg Q2W were included.

Arm/Group Title	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:	Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed	105	96	102
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	-1.76 (0.305)	-2.89 (0.266)	-3.04 (0.266)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.006
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.13
	Confidence Interval	(2-Sided) 95%; -1.92 to -0.33
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.404
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.002
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.29
	Confidence Interval	(2-Sided) 95%; -2.08 to -0.49
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.404
	Estimation Comments	[Not Specified]

12. Secondary Outcome

Title	Change From Baseline in Magnetic Resonance Imaging (MRI) of the Sacroiliac Joint (SIJ) Spondyloarthritis Research Consortium of Canada (SPARCC) Score
Description	Both left and right SIJ are scored for bone marrow edema. Each side has 6 slices and each slice has 6 scoring units, and each scoring unit has a score of 0 or 1. Total SIJ SPARCC scores can range from 0 to 72 with higher scores reflecting worse disease. LS Mean was derived from ANCOVA model with treatment, geographic region, screening MRI/CRP status and baseline value as fixed factors.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants with baseline and Week 16 SPARCC score. For inadequate responders who were treated with open label ixekizumab 80 mg Q2W, only data up to the time of initiation of open label of ixekizumab 80 mg Q2W were included.

Arm/Group Title	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:	Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed	90	85	92
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	-0.31 (0.539)	-3.38 (0.549)	-4.52 (0.530)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-3.07
	Confidence Interval	(2-Sided) 95%; -4.58 to -1.57
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.764
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-4.20
	Confidence Interval	(2-Sided) 95%; -5.68 to -2.72
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.751
	Estimation Comments	[Not Specified]

13. Secondary Outcome

Title	Change From Baseline in SPARCC Enthesitis Score
Description	The SPARCC enthesitis is an index used to measure the severity of enthesitis. The SPARCC assesses 16 sites for enthesitis using a score of "0" for no activity or "1" for activity. Sites assessed include Medial epicondyle (left/right [L/R]), Lateral epicondyle (L/R), Supraspinatus insertion into greater tuberosity of humerus (L/R), Greater trochanter (L/R), Quadriceps insertion into superior border of patella (L/R), Patellar ligament insertion into inferior pole of patella or tibial tubercle (L/R), Achilles tendon insertion into calcaneum (L/R), and Plantar fascia insertion into calcaneum (L/R). The SPARCC is the sum of all site scores (range 0 to 16). Higher scores indicate more severe enthesitis. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value visit, baseline value-by-visit and treatment-by-visit interaction as fixed factors.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants with a baseline SPARCC score >0. For inadequate responders who were treated with open label ixekizumab 80 mg Q2W, only data up to the time of initiation of open label of ixekizumab 80 mg Q2W were included.

Arm/Group Title	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:	Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed	86	65	74
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	-2.87 (0.447)	-2.99 (0.427)	-3.14 (0.407)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.849
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 95%; -1.35 to 1.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.621
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.648
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.28
	Confidence Interval	(2-Sided) 95%; -1.48 to 0.93
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.608
	Estimation Comments	[Not Specified]

14. Secondary Outcome

Title	Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)
Description	BASFI is a participant-reported assessment that establishes a participant's functional baseline and subsequent response to treatment. Participants were asked to rate the difficulty associated with 10 individual basic functional activities. Participant responded to each question using a NRS scale (range 0 to 10), with a higher score indicating worse functioning. The participant's final BASFI score is the mean of the 10 item scores with the minimum value of 0 and a possible maximum value of 10, with a higher score indicating worse function. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants. For inadequate responders who were treated with open label ixekizumab 80 mg Q2W, only data up to the time of initiation of open label of ixekizumab 80 mg Q2W were included.

Arm/Group Title	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:	Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed	105	96	102
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	-1.57 (0.333)	-2.63 (0.292)	-2.75 (0.291)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.018
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.06
	Confidence Interval	(2-Sided) 95%; -1.93 to -0.18
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.443
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.008
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.18
	Confidence Interval	(2-Sided) 95%; -2.05 to -0.31
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.442
	Estimation Comments	[Not Specified]

15. Secondary Outcome

Title	Percentage of Participants Achieving ASDAS Inactive Disease
Description	ASDAS is a composite index to assess disease activity in axSpA. ASDAS Inactive Disease is defined as a score of less than (<)1.3. The parameters used for the ASDAS (with CRP as acute phase reactant) are total back pain, patient global, peripheral pain/swelling, duration of morning stiffness and CRP in mg/L. The ASDAScrp is calculated with the following equation: 0.121×total back pain+0.110×patient global+0.073×peripheral pain/swelling+0.058×duration of morning stiffness+0.579×Ln(CRP+1). (CRP is in mg/liter, the range of other variables is from 0(normal) to 10(very severe); Ln represents the natural logarithm). Data from five variables combined to yield a score (0.6361 to no defined upper limit), where higher the score worse the disease activity.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants. For inadequate responders who were treated with open label ixekizumab 80 mg Q2W, only data up to the time of initiation of open label of ixekizumab 80 mg Q2W were included. Missing data was imputed using the NRI method.

Arm/Group Title	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:	Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed	105	96	102
Measure Type: Number; Unit of Measure: percentage of participants
	2.9	13.5	10.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0011
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.33
	Confidence Interval	(2-Sided) 96%; 1.47 to 19.40
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.031
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.22
	Confidence Interval	(2-Sided) 95%; 1.14 to 15.66
	Estimation Comments	[Not Specified]

16. Secondary Outcome

Title	Change From Baseline in the Measure of High Sensitivity C-Reactive Protein (CRP)
Description	High-sensitivity C-reactive protein (hs-CRP) was the measure of acute phase reactant and was measured with a high sensitivity assay at the central laboratory to help assess the effect of ixekizumab on disease activity. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants. For inadequate responders who were treated with open label ixekizumab 80 mg Q2W, only data up to the time of initiation of open label of ixekizumab 80 mg Q2W were included.

Arm/Group Title	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:	Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed	105	96	102
Least Squares Mean (Standard Error); Unit of Measure: milligram/liter (mg/L)
	-4.804 (2.0370)	-8.611 (2.0028)	-7.547 (1.9654)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.183
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-3.807
	Confidence Interval	(2-Sided) 95%; -9.418 to 1.804
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.8507
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.331
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.743
	Confidence Interval	(2-Sided) 95%; -8.294 to 2.807
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.8202
	Estimation Comments	[Not Specified]

17. Secondary Outcome

Title	Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI)
Description	Bath Ankylosing Spondylitis Metrology Index (BASMI) is a combined index comprising the following 5 clinical measurements of spinal mobility in participants with axSpA: 1) Lateral spinal flexion 2) Tragus-to-wall distance 3) Lumbar flexion (modified Schrober) 4) Maximal intermalleolar distance, and 5) Cervical rotation. The BASMI includes these 5 measurements that were each scaled to a score of 0 to 10 depending on the result of the assessment (BASMI linear function). The average score of the 5 assessments gives the BASMI linear result. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants. For inadequate responders who were treated with open label ixekizumab 80 mg Q2W, only data up to the time of initiation of open label of ixekizumab 80 mg Q2W were included.

Arm/Group Title	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:	Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed	105	96	102
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	-0.17 (0.112)	-0.56 (0.097)	-0.48 (0.097)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.008
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 95%; -0.69 to -0.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.148
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.038
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.31
	Confidence Interval	(2-Sided) 95%; -0.60 to -0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.148
	Estimation Comments	[Not Specified]

18. Secondary Outcome

Title	Change From Baseline in Chest Expansion
Description	While participants have their hands resting on or behind the head, the assessor has measured the chest's encircled length by centimeter at the fourth intercostal level anteriorly. The difference between maximal inspiration and expiration in centimeters was recorded. Two tries were recorded. The better measurement (larger difference) of 2 tries (in centimeters) was used for analyses. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants. For inadequate responders who were treated with open label ixekizumab 80 mg Q2W, only data up to the time of initiation of open label of ixekizumab 80 mg Q2W were included.

Arm/Group Title	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:	Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed	105	96	102
Least Squares Mean (Standard Error); Unit of Measure: centimeter (cm)
	0.57 (0.253)	0.62 (0.206)	0.91 (0.209)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.871
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -0.59 to 0.70
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.325
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.295
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.34
	Confidence Interval	(2-Sided) 95%; -0.30 to 0.99
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.327
	Estimation Comments	[Not Specified]

19. Secondary Outcome

Title	Change From Baseline in Occiput to Wall Distance
Description	The participant is to make a maximum effort to touch the head against the wall when standing with heels and back against the wall (occiput). Then the distance from occiput to wall is measured. Two tries will be recorded. The better (smaller) measurement of 2 tries (in centimeters) will be used for analyses. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants. For inadequate responders who were treated with open label ixekizumab 80 mg Q2W, only data up to the time of initiation of open label of ixekizumab 80 mg Q2W were included.

Arm/Group Title	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:	Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed	105	96	102
Least Squares Mean (Standard Error); Unit of Measure: cm
	0.04 (0.312)	-0.42 (0.257)	-0.73 (0.259)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.257
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.46
	Confidence Interval	(2-Sided) 95%; -1.26 to 0.34
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.406
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.057
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.77
	Confidence Interval	(2-Sided) 95%; -1.56 to 0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.402
	Estimation Comments	[Not Specified]

20. Secondary Outcome

Title	Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)
Description	Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) is an index used to measure the severity of enthesitis. The MASES assesses 13 sites for enthesitis using a score of "0" for no activity or "1" for activity. Sites assessed included costochondral 1 (right/left [R/L]), costochondral 7 (R/L), spinal iliaca anterior superior (R/L), crista iliaca (R/L), spina iliaca posterior (R/L), processus spinosus L5, and achilles tendon proximal insertion (R/L). The MASES is the sum of all site scores (range 0 to 13); higher scores indicate more severe enthesitis. LS mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants with baseline Mases score > 0. For inadequate responders who were treated with open label ixekizumab 80 mg Q2W, only data up to the time of initiation of open label of ixekizumab 80 mg Q2W were included.

Arm/Group Title	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:	Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed	105	96	102
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	-2.34 (0.361)	-3.21 (0.342)	-3.19 (0.336)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.082
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.87
	Confidence Interval	(2-Sided) 95%; -1.85 to 0.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.496
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.088
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.85
	Confidence Interval	(2-Sided) 95%; -1.82 to 0.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.493
	Estimation Comments	[Not Specified]

21. Secondary Outcome

Title	Change From Baseline in Severity of Peripheral Arthritis by Tender (TJC) and Swollen Joint Count (SJC) Scores of 44 Joints
Description	The number of tender and painful joints was determined by examination of 46 joints (23 joints on each side of the participants body). The 46 joints are assessed and classified as tender or not tender. Sum of all joints checked to be tender/painful divided by number of evaluable joints which is multiplied by 46 to obtain TJC score. The scores ranges from 0 (no tender/painful joints) to 46 (all joints tender/painful). Swollen joint count SJC was determined by examination of 44 joints (22 joints on each side of the participants body). The joints are classified as swollen or not swollen. Sum of all joints checked to be swollen divided by number of evaluable joints which is multiplied by 44 to obtain SJC score. Score ranges from 0 (not swollen) to 44 (all joints swollen). LS mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status and baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants with baseline TJC>0 for the TJC analysis. All randomized participants with baseline SJC>0 for the SJC analysis. For inadequate responders who were treated with open label ixekizumab 80 mg Q2W, only data up to the time of initiation of open label of ixekizumab 80 mg Q2W were included.

Arm/Group Title		Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:		Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed		105	96	102
Least Squares Mean (Standard Error); Unit of Measure: joint counts
TJC	Number Analyzed	83 participants	70 participants	86 participants
		-0.59 (1.039)	-2.38 (0.993)	-4.12 (0.916)
SJC	Number Analyzed	50 participants	51 participants	57 participants
		-3.66 (0.261)	-4.63 (0.237)	-4.41 (0.228)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	TJC
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.219
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.79
	Confidence Interval	(2-Sided) 95%; -4.66 to 1.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.442
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	TJC
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.013
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-3.53
	Confidence Interval	(2-Sided) 95%; -6.30 to -0.76
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.388
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	SJC
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.009
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.97
	Confidence Interval	(2-Sided) 95%; -1.68 to -0.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.355
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	SJC
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.034
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.76
	Confidence Interval	(2-Sided) 95%; -1.46 to -0.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.348
	Estimation Comments	[Not Specified]

22. Secondary Outcome

Title	Number of Participants With Anterior Uveitis
Description	Number of participants with anterior uveitis. Anterior uveitis is an inflammation of the middle layer of the eye which includes the iris (colored part of the eye) and the adjacent tissue, known as the ciliary body.
Time Frame	Baseline through Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants regardless of history of anterior uveitis. For inadequate responders who were treated with open label ixekizumab 80 mg Q2W, only data up to the time of initiation of open label of ixekizumab 80 mg Q2W were included.

Arm/Group Title	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:	Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed	105	96	102
Measure Type: Count of Participants; Unit of Measure: Participants
	2	1	2

23. Secondary Outcome

Title	Change From Baseline in the Fatigue Numeric Rating Scale (NRS) Score
Description	The Fatigue Severity NRS is a participant-administered, single-item, 11-point horizontal scale anchored at 0 and 10, with 0 representing "no fatigue" and 10 representing "as bad as you can imagine". Participants rate their fatigue (feeling tired or worn out) by circling the one number that describes their worst level of fatigue during the previous 24 hours. LS Mean was derived from MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants. For inadequate responders who were treated with open label ixekizumab 80 mg Q2W, only data up to the time of initiation of open label of ixekizumab 80 mg Q2W were included.

Arm/Group Title	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:	Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed	105	96	102
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	-2.1 (0.38)	-2.6 (0.32)	-2.7 (0.32)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.325
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.5 to 0.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.50
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.206
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.6 to 0.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.50
	Estimation Comments	[Not Specified]

24. Secondary Outcome

Title	Change From Baseline in ASAS Health Index (ASAS HI)
Description	ASAS-HI is a disease-specific health-index instrument designed to assess the impact of interventions for SpA, including axSpA. The 17-item instrument has scores ranging from 0 (good health) to 17 (poor health). Each item consists of one question that the participant needs to respond to with either "I agree" (score of 1) or "I do not agree" (score of 0). A score of "1" is given where the item is affirmed, indicating adverse health. All item scores are summed to give a total score or index. LS Mean was derived MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants. For inadequate responders who were treated with open label ixekizumab 80 mg Q2W, only data up to the time of initiation of open label of ixekizumab 80 mg Q2W were included.

Arm/Group Title	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:	Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed	105	96	102
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	-2.57 (0.455)	-3.16 (0.395)	-3.54 (0.396)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.330
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.59
	Confidence Interval	(2-Sided) 95%; -1.77 to 0.60
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.601
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.110
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.97
	Confidence Interval	(2-Sided) 95%; -2.15 to 0.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.602
	Estimation Comments	[Not Specified]

25. Secondary Outcome

Title	Change From Baseline in the Jenkins Sleep Evaluation Questionnaire (JSEQ)
Description	Jenkins Sleep Evaluation Questionnaire (JSEQ) is a 4 item scale designed to estimate sleep problems in clinical research. The JSEQ assesses the frequency of sleep disturbance in 4 categories: 1) trouble falling asleep, 2) waking up several times during the night, 3) having trouble staying asleep (including waking up far too early), and 4) waking up after the usual amount of sleep feeling tired and worn out. Patients report the numbers of days they experience each of these problems in the past month on a 6 point Likert Scale ranging from 0 = "no days" to 5 = "22-30 days. The total JSEQ score ranges from 0 to 20, with higher scores indicating greater sleep disturbance. LS Mean was derived from using MMRM with treatment, geographic region, screening MRI/CRP status, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants. For inadequate responders who were treated with open label ixekizumab 80 mg Q2W, only data up to the time of initiation of open label of ixekizumab 80 mg Q2W were included.

Arm/Group Title	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:	Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed	105	96	102
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
	-2.9 (0.63)	-3.6 (0.52)	-3.6 (0.53)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.348
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -2.4 to 0.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.81
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.386
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -2.3 to 0.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.82
	Estimation Comments	[Not Specified]

26. Secondary Outcome

Title	Change From Baseline in the Work Productivity Activity Impairment Spondyloarthritis (WPAI-SpA) Scores
Description	The WPAI-SpA consists of 6 questions to determine employment status, hours missed from work because of SpA, hours missed from work for other reasons, hours actually worked, the degree to which SpA affected work productivity while at work, and the degree to which SpA affected activities outside of work. The WPAI-SpA has been validated in the rad-axSpA patient population. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. The computed percentage range for each sub-scale was from 0-100, with higher scores indicating greater impairment and less productivity. LS Mean was derived from ANCOVA with treatment, geographic region, screening MRI/CRP status and baseline value.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants. For inadequate responders who were treated with open label ixekizumab 80 mg Q2W, only data up to the time of initiation of open label of ixekizumab 80 mg Q2W were included. Missing data were imputed using the modified baseline observation carried forward (mBOCF).

Arm/Group Title	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:	Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed	105	96	102
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
Overall Impairment Score	-13.20 (3.386)	-26.96 (3.439)	-19.49 (3.221)
Percentage of absenteeism	-3.11 (2.215)	-9.01 (2.257)	-7.26 (2.151)
Percentage of presenteeism	-12.40 (3.200)	-26.01 (3.245)	-18.61 (3.047)
Percentage of impairment in activities	-14.42 (2.584)	-25.05 (2.617)	-24.41 (2.567)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	Overall Impairment Score
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.005
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-13.76
	Confidence Interval	(2-Sided) 95%; -23.32 to -4.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.835
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	Overall Impairment Score
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.183
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-6.29
	Confidence Interval	(2-Sided) 95%; -15.58 to 3.00
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.697
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	Percentage of absenteeism
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.060
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-5.90
	Confidence Interval	(2-Sided) 95%; -12.05 to 0.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.114
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	Percentage of absenteeism
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.182
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-4.15
	Confidence Interval	(2-Sided) 95%; -10.27 to 1.97
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.098
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	Percentage of presentism
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.003
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-13.61
	Confidence Interval	(2-Sided) 95%; -22.62 to -4.60
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.558
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	Percentage of presentism
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.164
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-6.21
	Confidence Interval	(2-Sided) 95%; -15.00 to 2.58
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.446
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q4W
	Comments	Percentage of Impairment in Activities Performed Outside of Work
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.004
	Comments	[Not Specified]
	Method	LS Mean Difference
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-10.63
	Confidence Interval	(2-Sided) 95%; -17.85 to -3.41
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.669
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Ixekizumab 80 mg Q2W
	Comments	Percentage of Impairment in Activities Performed Outside of Work
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.006
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-9.99
	Confidence Interval	(2-Sided) 95%; -17.12 to -2.86
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.621
	Estimation Comments	[Not Specified]

27. Secondary Outcome

Title	Change From Baseline in ASAS-Nonsteroidal Anti-Inflammatory Drug (NSAID) Score
Description	ASAS-NSAID score is used to present the NSAID intake by considering the type of NSAID, the total dose, & the number of days taking NSAID during a period of interest (PI). For NSAID equivalent scoring system, range is from 0 to 100, the higher the score, the greater the NSAID intake. ASAS-NSAID score= (equivalent NSAID score) x (days of intake during PI) x (days per week)/(PI in days).
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants who had NSAID (including COX-2 Inhibitor) intake at Baseline. For inadequate responders who were treated with open label ixekizumab 80 mg Q2W, only data up to the time of initiation of open label of ixekizumab 80 mg Q2W were included.

Arm/Group Title	Placebo	Ixekizumab 80 mg Q4W	Ixekizumab 80 mg Q2W
Arm/Group Description:	Participants received placebo as 2 SC injections Q2W to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 and placebo followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.	Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.
Overall Number of Participants Analyzed	96	81	95
Mean (Standard Deviation); Unit of Measure: score on a scale
	-8.89 (29.986)	-7.91 (34.257)	-5.33 (20.935)

28. Secondary Outcome

Title	Number of Participants With Treatment Emergent (TE) Anti-Ixekizumab Antibodies
Description	A treatment-emergent positive anti-drug antibody (TE-ADA+) participant will be defined as a 4-fold increase over a positive baseline antibody titer (Tier 3); or for a negative baseline titer, a participant with an increase from the baseline to a level of ≥ 1:10.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

All randomized participant who received at least one dose of ixekizumab during the study and had an evaluable baseline sample and at least 1 evaluable post baseline sample.

Arm/Group Title	Ixe80Q2W-Q2W	Ixe80Q4W-Q4W	PBO-Ixe80Q2W	Ixe80Q4W-Q2W
Arm/Group Description:	Participants received a starting dose of 80 ixekizumab as an SC injection at week 0 followed by 80 mg of ixe every two weeks (Q2W) week 2 to week 52.	Participants received a starting dose of 80 ixekizumab as an SC injection followed by 80 mg of ixekizumab Q4W week 4 to week 52.	Participants who received placebo in double blind period and were inadequate responders switched to ixekizumab 80 mg Q2W open-label.	Participants who received ixekizumab 80 mg Q4W in double blind period and were inadequate responders switched to ixekizumab 80 mg Q2W open label.
Overall Number of Participants Analyzed	102	56	62	40
Measure Type: Count of Participants; Unit of Measure: Participants
	14	5	8	2

29. Secondary Outcome

Title	Pharmacokinetics (PK): Trough Concentration at Steady State (Ctrough ss)
Description	PK trough serum concentration samples were collected at steady state (Ctrough ss)
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

All randomized participants who had evaluable PK data.

Arm/Group Title	IxeQ2W (80S)/IxeQ2W	IxeQ2W (80S)/IxeQ2W Open Label	IxeQ2W (160S)/IxeQ2W	IxeQ2W (160s)/IxeQ2W Open Label	IxeQ4W (80S) IxeQ4W	IxeQ4W (80S)/IxeQ2W Open Label	IxeQ4W(160S)/IxeQ4W	IxeQ4W (160S) IxeQ2W Open Label	PBO/IxeQ2W Open Label
Arm/Group Description:	Ixekizumab was administered subcutaneously every 2 weeks with an 80 mg starting dose at week 0.	Ixekizumab was administered every 2 weeks with an 80 mg starting dose at Week 0, then ixekizumab 80 mg Q2W open label between Week 16 and Week 52.	Ixekizumab was administered subcutaneously every 2 weeks with an 160 mg starting dose at week 0.	Ixekizumab was administered subcutaneously every 2 weeks with an 160 mg starting dose at week 0 then ixekizumab 80 mg Q2W open label between Week 16 and Week 52.	Ixekizumab was administered subcutaneously every 4 weeks with an 80 mg starting dose at week 0.	Ixekizumab was administered subcutaneously every 4 weeks with an 80 mg starting dose at week 0 then ixekizumab 80 mg Q2W open label between Week 16 and Week 52.	Ixekizumab was administered subcutaneously every 4 weeks with an 160 mg starting dose at week 0.	Ixekizumab was administered subcutaneously every 4 weeks with an 160 mg starting dose at week 0 then ixekizumab 80 mg Q2W open label between Week 16 and Week 52.	Placebo was administered at week 0 then ixekizumab 80 mg Q2W open label between Week 16 and Week 52.
Overall Number of Participants Analyzed	32	18	28	24	28	19	28	21	55
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: microgram/milliliter (μg/mL)
	7.88; (73%)	9.56; (60%)	10.3; (61%)	10.4; (72%)	2.88; (49%)	6.45; (124%)	3.54; (79%)	11.5; (53%)	9.25; (66%)

Adverse Events

Time Frame

Up to 76 Weeks

Adverse Event Reporting Description

All randomized participants who received at least one dose of study drug during the study. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.

Arm/Group Title

Placebo Double-Blind Period

Ixekizumab 80 mg Q4W Double-Blind Period

Ixekizumab 80 mg Q2W Double-Blind Period

PBO IR/IxeQ2W Open Label

Ixe80Q4WIR/Ixe80Q2W Open Label

Ixe80Q2WIR/Ixe80Q2W Open Label

Other Biologic Open Label

Placebo Post Treatment Follow-Up Period

Ixekizumab 80 mg Q4W Post Treatment Follow-Up Period

Ixekizumab 80 mg Q2W Post Treatment Follow-Up Period

Other Biologic Post Treatment Follow-Up Period

Arm/Group Description

Participants received placebo as 2 SC injections Q2W to week 52.

Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every four weeks (Q4W) to week 52.

Participants received a starting dose of 80 or 160 mg of ixekizumab given SC at week 0 followed by 80 mg ixekizumab given SC every two weeks (Q2W) to week 52.

Participants who received placebo in double blind period and were inadequate responders as determined by investigators switched to ixekizumab 80 mg Q2W open label.

Participants who received ixekizumab 80 mg Q4W in double blind period and were inadequate responders as determined by investigators switched to ixekizumab 80 mg Q2W open label.

Participants who received ixekizumab 80 mg Q2W in double blind period and were inadequate responders as determined by investigators continued on the same regimen of ixekizumab 80 mg Q2W open label.

Participants who discontinued study treatment and were on other biologic therapy prior to entering Follow-up period

Participants discontinued the study early and entered the post-treatment follow-up period. Participants received placebo immediately prior to entering the post-treatment follow-up period.

Participants discontinued the study early and entered the post-treatment follow-up period. Participants received ixekizumab 80 mg Q4W immediately prior to entering the post-treatment follow-up period.

Participants discontinued the study early and entered the post-treatment follow-up period. Participants received ixekizumab 80 mg Q2W immediately prior to entering the post-treatment follow-up period.

Participants who discontinued study treatment and were on other biologic therapy prior to entering follow-up period.

All-Cause Mortality

Placebo Double-Blind Period

Ixekizumab 80 mg Q4W Double-Blind Period

Ixekizumab 80 mg Q2W Double-Blind Period

PBO IR/IxeQ2W Open Label

Ixe80Q4WIR/Ixe80Q2W Open Label

Ixe80Q2WIR/Ixe80Q2W Open Label

Other Biologic Open Label

Placebo Post Treatment Follow-Up Period

Ixekizumab 80 mg Q4W Post Treatment Follow-Up Period

Ixekizumab 80 mg Q2W Post Treatment Follow-Up Period

Other Biologic Post Treatment Follow-Up Period

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Total

0/104 (0.00%)

0/96 (0.00%)

0/102 (0.00%)

0/42 (0.00%)

0/40 (0.00%)

0/62 (0.00%)

0/5 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

0/28 (0.00%)

0/5 (0.00%)

Serious Adverse Events

Placebo Double-Blind Period

Ixekizumab 80 mg Q4W Double-Blind Period

Ixekizumab 80 mg Q2W Double-Blind Period

PBO IR/IxeQ2W Open Label

Ixe80Q4WIR/Ixe80Q2W Open Label

Ixe80Q2WIR/Ixe80Q2W Open Label

Other Biologic Open Label

Placebo Post Treatment Follow-Up Period

Ixekizumab 80 mg Q4W Post Treatment Follow-Up Period

Ixekizumab 80 mg Q2W Post Treatment Follow-Up Period

Other Biologic Post Treatment Follow-Up Period

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Total

1/104 (0.96%)

2/96 (2.08%)

1/102 (0.98%)

1/42 (2.38%)

0/40 (0.00%)

2/62 (3.23%)

0/5 (0.00%)

0/3 (0.00%)

0/5 (0.00%)

1/28 (3.57%)

0/5 (0.00%)

Gastrointestinal disorders

Abdominal pain † 1

0/104 (0.00%)

0

1/96 (1.04%)

1

0/102 (0.00%)

0

0/42 (0.00%)

0

0/40 (0.00%)

0

0/62 (0.00%)

0

0/5 (0.00%)

0

0/3 (0.00%)

0

0/5 (0.00%)

0

0/28 (0.00%)

0

0/5 (0.00%)

0

Immune system disorders

Anaphylactoid reaction † 1

1/104 (0.96%)

1

0/96 (0.00%)

0

0/102 (0.00%)

0

0/42 (0.00%)

0

0/40 (0.00%)

0

0/62 (0.00%)

0

0/5 (0.00%)

0

0/3 (0.00%)

0

0/5 (0.00%)

0

0/28 (0.00%)

0

0/5 (0.00%)

0

Infections and infestations

Erysipelas † 1

0/104 (0.00%)

0

1/96 (1.04%)

2

0/102 (0.00%)

0

0/42 (0.00%)

0

0/40 (0.00%)

0

0/62 (0.00%)

0

0/5 (0.00%)

0

0/3 (0.00%)

0

0/5 (0.00%)

0

0/28 (0.00%)

0

0/5 (0.00%)

0

Sinusitis † 1

0/104 (0.00%)

0

0/96 (0.00%)

0

0/102 (0.00%)

0

0/42 (0.00%)

0

0/40 (0.00%)

0

1/62 (1.61%)

1

0/5 (0.00%)

0

0/3 (0.00%)

0

0/5 (0.00%)

0

0/28 (0.00%)

0

0/5 (0.00%)

0

Musculoskeletal and connective tissue disorders

Axial spondyloarthritis † 1

0/104 (0.00%)

0

0/96 (0.00%)

0

0/102 (0.00%)

0

0/42 (0.00%)

0

0/40 (0.00%)

0

0/62 (0.00%)

0

0/5 (0.00%)

0

0/3 (0.00%)

0

0/5 (0.00%)

0

1/28 (3.57%)

1

0/5 (0.00%)

0

Intervertebral disc protrusion † 1

0/104 (0.00%)

0

0/96 (0.00%)

0

0/102 (0.00%)

0

0/42 (0.00%)

0

0/40 (0.00%)

0

1/62 (1.61%)

1

0/5 (0.00%)

0

0/3 (0.00%)

0

0/5 (0.00%)

0

0/28 (0.00%)

0

0/5 (0.00%)

0

Osteoarthritis † 1

0/104 (0.00%)

0

0/96 (0.00%)

0

0/102 (0.00%)

0

0/42 (0.00%)

0

0/40 (0.00%)

0

1/62 (1.61%)

1

0/5 (0.00%)

0

0/3 (0.00%)

0

0/5 (0.00%)

0

0/28 (0.00%)

0

0/5 (0.00%)

0

Nervous system disorders

Focal dyscognitive seizures † 1

0/104 (0.00%)

0

0/96 (0.00%)

0

0/102 (0.00%)

0

0/42 (0.00%)

0

0/40 (0.00%)

0

0/62 (0.00%)

0

0/5 (0.00%)

0

0/3 (0.00%)

0

0/5 (0.00%)

0

1/28 (3.57%)

1

0/5 (0.00%)

0

Psychiatric disorders

Major depression † 1

0/104 (0.00%)

0

0/96 (0.00%)

0

1/102 (0.98%)

2

0/42 (0.00%)

0

0/40 (0.00%)

0

0/62 (0.00%)

0

0/5 (0.00%)

0

0/3 (0.00%)

0

0/5 (0.00%)

0

0/28 (0.00%)

0

0/5 (0.00%)

0

Somatic symptom disorder † 1

0/104 (0.00%)

0

0/96 (0.00%)

0

0/102 (0.00%)

0

1/42 (2.38%)

1

0/40 (0.00%)

0

0/62 (0.00%)

0

0/5 (0.00%)

0

0/3 (0.00%)

0

0/5 (0.00%)

0

0/28 (0.00%)

0

0/5 (0.00%)

0

1 Term from vocabulary, MedDRA 22.0; † Indicates events were collected by systematic assessment

Other (Not Including Serious) Adverse Events

Frequency Threshold for Reporting Other Adverse Events

5%

Placebo Double-Blind Period

Ixekizumab 80 mg Q4W Double-Blind Period

Ixekizumab 80 mg Q2W Double-Blind Period

PBO IR/IxeQ2W Open Label

Ixe80Q4WIR/Ixe80Q2W Open Label

Ixe80Q2WIR/Ixe80Q2W Open Label

Other Biologic Open Label

Placebo Post Treatment Follow-Up Period

Ixekizumab 80 mg Q4W Post Treatment Follow-Up Period

Ixekizumab 80 mg Q2W Post Treatment Follow-Up Period

Other Biologic Post Treatment Follow-Up Period

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Total

31/104 (29.81%)

43/96 (44.79%)

47/102 (46.08%)

13/42 (30.95%)

15/40 (37.50%)

26/62 (41.94%)

3/5 (60.00%)

1/3 (33.33%)

1/5 (20.00%)

1/28 (3.57%)

0/5 (0.00%)

Eye disorders

Iritis † 1

0/104 (0.00%)

0

0/96 (0.00%)

0

0/102 (0.00%)

0

0/42 (0.00%)

0

0/40 (0.00%)

0

0/62 (0.00%)

0

0/5 (0.00%)

0

0/3 (0.00%)

0

1/5 (20.00%)

1

0/28 (0.00%)

0

0/5 (0.00%)

0

Gastrointestinal disorders

Abdominal pain upper † 1

1/104 (0.96%)

1

1/96 (1.04%)

1

1/102 (0.98%)

1

0/42 (0.00%)

0

3/40 (7.50%)

3

0/62 (0.00%)

0

0/5 (0.00%)

0

0/3 (0.00%)

0

0/5 (0.00%)

0

0/28 (0.00%)

0

0/5 (0.00%)

0

Nausea † 1

1/104 (0.96%)

1

1/96 (1.04%)

1

1/102 (0.98%)

1

4/42 (9.52%)

4

2/40 (5.00%)

2

0/62 (0.00%)

0

0/5 (0.00%)

0

0/3 (0.00%)

0

0/5 (0.00%)

0

0/28 (0.00%)

0

0/5 (0.00%)

0

General disorders

Influenza like illness † 1

2/104 (1.92%)

4

0/96 (0.00%)

0

0/102 (0.00%)

0

0/42 (0.00%)

0

0/40 (0.00%)

0

0/62 (0.00%)

0

0/5 (0.00%)

0

1/3 (33.33%)

1

0/5 (0.00%)

0

0/28 (0.00%)

0

0/5 (0.00%)

0

Injection site erythema † 1

1/104 (0.96%)

3

3/96 (3.13%)

7

4/102 (3.92%)

11

2/42 (4.76%)

5

0/40 (0.00%)

0

5/62 (8.06%)

6

0/5 (0.00%)

0

0/3 (0.00%)

0

0/5 (0.00%)

0

0/28 (0.00%)

0

0/5 (0.00%)

0

Injection site reaction † 1

4/104 (3.85%)

7

11/96 (11.46%)

24

17/102 (16.67%)

56

3/42 (7.14%)

11

3/40 (7.50%)

28

11/62 (17.74%)

63

0/5 (0.00%)

0

0/3 (0.00%)

0

0/5 (0.00%)

0

0/28 (0.00%)

0

0/5 (0.00%)

0

Infections and infestations

Bacterial vaginosis † 1

0/61 (0.00%)

0

1/46 (2.17%)

1

0/53 (0.00%)

0

0/28 (0.00%)

0

1/15 (6.67%)

1

2/41 (4.88%)

2

0/4 (0.00%)

0

0/1 (0.00%)

0

0/3 (0.00%)

0

0/19 (0.00%)

0

0/4 (0.00%)

0

Bronchitis † 1

3/104 (2.88%)

4

7/96 (7.29%)

7

2/102 (1.96%)

2

1/42 (2.38%)

1

1/40 (2.50%)

1

5/62 (8.06%)

5

0/5 (0.00%)

0

0/3 (0.00%)

0

0/5 (0.00%)

0

0/28 (0.00%)

0

0/5 (0.00%)

0

Nasopharyngitis † 1

8/104 (7.69%)

11

18/96 (18.75%)

26

16/102 (15.69%)

27

2/42 (4.76%)

3

7/40 (17.50%)

10

6/62 (9.68%)

8

1/5 (20.00%)

1

0/3 (0.00%)

0

0/5 (0.00%)

0

0/28 (0.00%)

0

0/5 (0.00%)

0

Pharyngitis † 1

4/104 (3.85%)

4

4/96 (4.17%)

5

2/102 (1.96%)

2

2/42 (4.76%)

2

3/40 (7.50%)

3

3/62 (4.84%)

3

0/5 (0.00%)

0

1/3 (33.33%)

1

0/5 (0.00%)

0

0/28 (0.00%)

0

0/5 (0.00%)

0

Sinusitis † 1

1/104 (0.96%)

1

2/96 (2.08%)

2

2/102 (1.96%)

2

3/42 (7.14%)

3

1/40 (2.50%)

1

1/62 (1.61%)

1

0/5 (0.00%)

0

0/3 (0.00%)

0

0/5 (0.00%)

0

0/28 (0.00%)

0

0/5 (0.00%)

0

Upper respiratory tract infection † 1

4/104 (3.85%)

4

4/96 (4.17%)

4

6/102 (5.88%)

7

2/42 (4.76%)

2

3/40 (7.50%)

4

4/62 (6.45%)

5