Study Comparing Etanercept (ETN) Against a Placebo for Etanercept on a Background Nonsteroidal Anti Inflammatory Drug (NSAIDs) in the Treatment of Early Spondyloarthritis (SpA) Patients Who do Not Have X-ray Structural Changes (EMBARK)

• ClinicalTrials.gov Identifier: NCT01258738
• Recruitment Status: Completed
• First Posted: December 13, 2010
• Results First Posted: October 19, 2015
• Last Update Posted: October 19, 2015
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Spondylitis, Ankylosing
• Interventions: Biological: etanercept; Drug: Background NSAID; Other: PLACEBO
• Enrollment: 225

Participant Flow

Recruitment Details	This was a multicenter study conducted at 48 centers in 14 countries.
Pre-assignment Details	Eligible participants were randomized to receive etanercept or placebo for 12 week controlled (double-blind) period. Participants completing 12 week period entered a 92 week open-label period.

Arm/Group Title	Etanercept	Placebo
Arm/Group Description	Participants were treated with etanercept subcutaneous injection weekly plus stable background non-steroidal anti-inflammatory drug (NSAID) at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.	Participants were treated with placebo subcutaneous injection weekly plus stable background NSAID at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.
Period Title: Double-blind Period
Started	111	114
Treated	111	113
Completed	102	107 [1]
Not Completed	9	7
Reason Not Completed
Did not meet inclusion criteria	3	3
Withdrawal by Subject	2	2
Protocol Violation	1	1
Adverse Event	3	1
[1] Only 106 participants entered the open label period.
Period Title: Open-label Period
Started	102	106
Completed	85	85
Not Completed	17	21
Reason Not Completed
Did not meet inclusion criteria	0	1
Insufficient clinical response	5	3
Lost to Follow-up	0	2
Withdrawal by Subject	5	6
Protocol Violation	2	2
Adverse Event	4	5
Other Reasons	0	1
Withdrawn due to pregnancy	1	1

Baseline Characteristics

Arm/Group Title		Etanercept	Placebo	Total
Arm/Group Description		Participants were treated with etanercept subcutaneous injection weekly plus stable background non-steroidal anti-inflammatory drug (NSAID) at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.	Participants were treated with placebo subcutaneous injection weekly plus stable background NSAID at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.	Total of all reporting groups
Overall Number of Baseline Participants		111	113	224
Baseline Analysis Population Description		The safety analysis set for the double blind period was defined as all randomized participants who took at least one dose of study medication. A total of 224 of the 225 randomized participants received study medication (1 subject randomized to the placebo group did not receive study medication).
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	111 participants	113 participants	224 participants
		31.7 (7.8)	32.0 (7.8)	31.9 (7.8)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	111 participants	113 participants	224 participants
	Female	41 36.9%	50 44.2%	91 40.6%
	Male	70 63.1%	63 55.8%	133 59.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving Ankylosing Spondylitis (ASAS) 40 Response at Week 12
Description	ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) in 4 domains: participant global assessment of disease activity, pain, function, inflammation. ASAS 40 = 40% improvement from baseline and an absolute change ≥ 20 units on a 0-100 scale (0 = no disease activity, 100 = high disease activity) for ≥ 3 domains, and no worsening in remaining domain.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (mITT) population defined as all randomized participants who took at least one dose of study drug, had at least one on-therapy evaluation and met the ASAS classification criteria for axial spondyloarthritis (AxSpA). Missing data were imputed through last observation carried forward (LOCF) approach.

Arm/Group Title	Etanercept	Placebo
Arm/Group Description:	Participants were treated with etanercept subcutaneous injection weekly plus stable background non-steroidal anti-inflammatory drug (NSAID) at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.	Participants were treated with placebo subcutaneous injection weekly plus stable background NSAID at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.
Overall Number of Participants Analyzed	105	108
Measure Type: Number; Unit of Measure: Percentage of participants
	32.38	15.74

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	The null hypothesis was that the efficacy of etanercept was not different from placebo as measured by the proportion of subjects achieving an ASAS 40 response after 12 weeks of treatment. The alternative hypothesis was that the efficacy of etanercept was different from placebo. The primary endpoint was tested at 2-sided alpha = 0.05 significance level. Comparative analysis was carried out for Week 12 data only.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0062
	Comments	P-value <0.05 was required to declare statistical significance.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	16.64
	Confidence Interval	(2-Sided) 95%; 5.36 to 27.92
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Percentage of Participants Achieving ASAS 40 Response at Time Points
Description	ASAS measures symptomatic improvement in AS in 4 domains: participant global assessment of disease activity, pain, function, inflammation. ASAS 40 = 40% improvement from baseline and an absolute change ≥ 20 units on a 0-100 scale (0 = no disease activity, 100 = high disease activity) for ≥ 3 domains, and no worsening in remaining domain.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description

mITT population defined as all randomized participants who took at least one dose of study drug, had at least one on-therapy evaluation and met the ASAS classification criteria for AxSpA. Missing data were imputed through LOCF approach.

Arm/Group Title	Etanercept	Placebo
Arm/Group Description:	Participants were treated with etanercept subcutaneous injection weekly plus stable background non-steroidal anti-inflammatory drug (NSAID) at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.	Participants were treated with placebo subcutaneous injection weekly plus stable background NSAID at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.
Overall Number of Participants Analyzed	105	108
Measure Type: Number; Unit of Measure: Percentage of participants
Week 2 (N=105, 106)	15.24	3.77
Week 4 (N=105, 108)	20.00	14.81
Week 8 (N=105, 108)	28.57	15.74
Week 12 (N= 105, 108)	33.33	14.81
Week 16 (N= 100, 105)	42.00	38.10
Week 24 (N= 100, 105)	44.00	51.43
Week 32 (N= 100, 105)	47.00	52.38
Week 40 (N= 100, 105)	55.00	53.33
Week 48 (N= 100, 105)	52.00	53.33
Week 56 (N= 100, 105)	52.00	59.05
Week 68 (N= 100, 105)	54.00	58.10
Week 80 (N= 100, 105)	49.00	58.10
Week 92 (N= 100, 105)	57.00	61.90
Week 104 (N= 100, 105)	56.00	61.90

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 2
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0059
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	11.46
	Confidence Interval	(2-Sided) 95%; 3.69 to 19.24
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 4
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3786
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	5.19
	Confidence Interval	(2-Sided) 95%; -4.98 to 15.35
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 8
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0304
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	12.83
	Confidence Interval	(2-Sided) 95%; 1.79 to 23.87
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0023
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	18.52
	Confidence Interval	(2-Sided) 95%; 7.29 to 29.75
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Percentage of Participants Achieving ASAS 20 Response at Time Points
Description	ASAS measures symptomatic improvement in AS in 4 domains: participant global assessment of disease activity, pain, function, inflammation. ASAS 20 = 20% improvement from baseline and an absolute change ≥ 10 units on a 0-100 scale (0=no disease activity; 100 = high disease activity) for ≥ 3 domains, and no worsening in remaining domain.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description

mITT population defined as all randomized participants who took at least one dose of study drug, had at least one on-therapy evaluation and met the ASAS classification criteria for AxSpA. Missing data were imputed through LOCF approach.

Arm/Group Title	Etanercept	Placebo
Arm/Group Description:	Participants were treated with etanercept subcutaneous injection weekly plus stable background non-steroidal anti-inflammatory drug (NSAID) at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.	Participants were treated with placebo subcutaneous injection weekly plus stable background NSAID at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.
Overall Number of Participants Analyzed	105	109
Measure Type: Number; Unit of Measure: Percentage of participants
Week 2 (N = 105, 106)	30.48	16.04
Week 4 (N = 105, 108)	37.14	26.85
Week 8 (N = 105, 108)	48.57	37.96
Week 12 (N = 105, 109)	52.38	36.70
Week 16 (N= 100, 105)	64.00	65.71
Week 24 (N = 100, 105)	65.00	71.43
Week 32 (N = 100, 105)	64.00	71.43
Week 40 (N = 100, 105)	73.00	73.33
Week 48 (N = 100, 105)	71.00	72.38
Week 56 (N = 100, 105)	70.00	76.19
Week 68 (N = 100, 105)	69.00	76.19
Week 80 (N = 100, 105)	65.00	70.48
Week 92 (N = 100, 105)	71.00	74.29
Week 104 (N = 100, 105)	70.00	79.05

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 2
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0189
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	14.44
	Confidence Interval	(2-Sided) 95%; 3.20 to 25.68
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 4
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0983
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	10.29
	Confidence Interval	(2-Sided) 95%; -2.17 to 22.75
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 8
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0867
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	10.61
	Confidence Interval	(2-Sided) 95%; -2.63 to 23.84
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0195
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	16.27
	Confidence Interval	(2-Sided) 95%; 3.10 to 29.43
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Percentage of Participants Achieving ASAS 5/6 Response at Time Points
Description	ASAS 5/6 consists of 6 domains: the 4 used in ASAS 20 (participant global assessment of disease activity, pain, function, inflammation measured on a 0-100 scale, where 0 = no disease activity and 100 = high disease activity) plus spinal mobility and an acute phase reactant, C Reactive Protein (CRP). Achieving ASAS 5/6 requires a 20% improvement compared to baseline in ≥ 5 domains and no worsening in the remaining domain.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description

mITT population defined as all randomized participants who took at least one dose of study drug, had at least one on-therapy evaluation and met the ASAS classification criteria for AxSpA. Missing data were imputed through LOCF approach.

Arm/Group Title	Etanercept	Placebo
Arm/Group Description:	Participants were treated with etanercept subcutaneous injection weekly plus stable background non-steroidal anti-inflammatory drug (NSAID) at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.	Participants were treated with placebo subcutaneous injection weekly plus stable background NSAID at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.
Overall Number of Participants Analyzed	105	109
Measure Type: Number; Unit of Measure: Percentage of participants
Week 2 (N = 102, 105)	15.69	2.86
Week 4 (N = 103, 107)	23.30	8.41
Week 8 (N = 103, 107)	33.01	11.21
Week 12 (N = 105, 109)	33.01	10.38
Week 16 (N = 100, 105)	37.00	34.29
Week 24 (N = 100, 105)	41.00	42.86
Week 32 (N = 100, 105)	40.00	40.95
Week 40 (N = 100, 105)	45.00	40.95
Week 48 (N = 100, 105)	49.00	45.71
Week 56 (N = 100, 105)	42.00	45.71
Week 68 (N = 100, 105)	42.00	43.81
Week 80 (N = 100, 105)	39.00	37.14
Week 92 (N = 100, 105)	46.00	47.62
Week 104 (N = 100, 105)	43.00	40.95

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	22.63
	Confidence Interval	(2-Sided) 95%; 11.85 to 33.41
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 2
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0021
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	12.83
	Confidence Interval	(2-Sided) 95%; 5.09 to 20.57
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 4
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0020
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	14.89
	Confidence Interval	(2-Sided) 95%; 5.18 to 24.60
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 8
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	21.79
	Confidence Interval	(2-Sided) 95%; 10.92 to 32.67
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Mean Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) High Sensitivity CRP (hsCRP) Score at Time Points
Description	ASDAS includes CRP (mg/L) or ESR (mm/hr); Apart from the value of CRP or ESR, the four additional self-reported items (rated on 0-10cm VAS or 0-10 numerical rating scale [NRS]) included in this index are back pain, duration of morning stiffness, peripheral pain/swelling and patient global assessment of disease activity. The ASDAS scores are then calculated as follows: ASDAS_CRP = (0.121 x total back pain) + (0.110 x subject global) + (0.073 x peripheral pain/swelling) + (0.058 x duration of morning stiffness) + (0.579 x Ln(CRP+1)). And ASDAS_ESR: (0.079 x total back pain) + (0.113 x subject global) + (0.086 x peripheral pain/swelling) + (0.069 x duration of morning stiffness) + (0.293 x √ESR). In addition, the proportion of participants who achieve inactive disease based on the ASDAS will be determined for each group. Inactive disease is defined as an ASDAS score <1.3.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description

mITT population defined as all randomized participants who took at least one dose of study drug, had at least one on-therapy evaluation and met the ASAS classification criteria for AxSpA. Missing data were imputed through LOCF approach.

Arm/Group Title	Etanercept	Placebo
Arm/Group Description:	Participants were treated with etanercept subcutaneous injection weekly plus stable background non-steroidal anti-inflammatory drug (NSAID) at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.	Participants were treated with placebo subcutaneous injection weekly plus stable background NSAID at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.
Overall Number of Participants Analyzed	105	108
Mean (Standard Error); Unit of Measure: Units on a scale
Week 2 (N = 104, 106)	-0.74 (0.10)	-0.20 (0.10)
Week 4 (N = 104, 108)	-0.92 (0.11)	-0.30 (0.10)
Week 8 (N = 104, 108)	-1.09 (0.13)	-0.48 (0.12)
Week 12 (N= 104, 108)	-1.27 (0.11)	-0.63 (0.08)
Week 16 (N= 99, 104)	-1.41 (0.11)	-1.35 (0.11)
Week 24 (N= 99, 104)	-1.48 (0.11)	-1.55 (0.11)
Week 32 (N= 99, 104)	-1.44 (0.11)	-1.52 (0.11)
Week 40 (N= 99, 104)	-1.64 (0.11)	-1.60 (0.12)
Week 48 (N= 99, 104)	-1.62 (0.11)	-1.63 (0.12)
Week 56 (N= 99, 104)	-1.61 (0.12)	-1.65 (0.11)
Week 68 (N= 99, 104)	-1.60 (0.11)	-1.65 (0.11)
Week 80 (N= 99, 104)	-1.53 (0.12)	-1.61 (0.12)
Week 92 (N= 99, 104)	-1.63 (0.12)	-1.70 (0.12)
Week 104 (N= 99, 104)	-1.59 (0.12)	-1.68 (0.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	All within group comparisons to baseline were <0.001, from paired t-test. For open-label period results include unadjusted mean changes and standard errors, no covariate adjustments were applied.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 2
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.54
	Confidence Interval	(2-Sided) 95%; -0.74 to -0.34
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 4
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.61
	Confidence Interval	(2-Sided) 95%; -0.81 to -0.41
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 8
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.61
	Confidence Interval	(2-Sided) 95%; -0.85 to -0.37
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Percentage of Participants Achieving ASAS Partial Remission at Time Points
Description	Partial remission defined as a score of 20 units or less (on a scale of 0-100, where 0 = no disease activity and 100 = high disease activity) in each of the 4 Assessment in ASAS domains: participant global assessment of disease activity, pain, function, and inflammation. For scale, 100 = high disease activity.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description

mITT population defined as all randomized participants who took at least one dose of study drug, had at least one on-therapy evaluation and met the ASAS classification criteria for AxSpA. Missing data were imputed through LOCF approach.

Arm/Group Title	Etanercept	Placebo
Arm/Group Description:	Participants were treated with etanercept subcutaneous injection weekly plus stable background non-steroidal anti-inflammatory drug (NSAID) at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.	Participants were treated with placebo subcutaneous injection weekly plus stable background NSAID at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.
Overall Number of Participants Analyzed	105	109
Measure Type: Number; Unit of Measure: Percentage of participants
Week 2 (N = 105, 108)	11.43	2.78
Week 4 (N = 105, 109)	10.48	3.67
Week 8 (N = 105, 109)	21.90	9.17
Week 12 (N = 105, 109)	24.76	11.93
Week 16 (N = 100, 105)	29.00	28.57
Week 24 (N = 100, 105)	32.00	42.86
Week 32 (N = 100, 105)	28.00	41.90
Week 40 (N = 100, 105)	40.00	45.71
Week 48 (N = 100, 105)	38.00	37.14
Week 56 (N = 100, 105)	40.00	43.81
Week 68 (N = 100, 105)	37.00	48.57
Week 80 (N = 100, 105)	34.00	49.52
Week 92 (N = 100, 105)	39.00	49.52
Week 104 (N = 100, 105)	40.00	57.14

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0209
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	12.84
	Confidence Interval	(2-Sided) 95%; 2.58 to 23.09
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 2
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0179
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	8.65
	Confidence Interval	(2-Sided) 95%; 1.82 to 15.48
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 4
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0611
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	6.81
	Confidence Interval	(2-Sided) 95%; -0.03 to 13.65
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 8
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0141
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	12.73
	Confidence Interval	(2-Sided) 95%; 3.14 to 22.32
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	All within group comparisons to baseline were <0.001, from paired t-test. For open-label period results include unadjusted mean changes and standard errors, no covariate adjustments were applied.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

7. Secondary Outcome

Title	Time to ASAS Partial Remission
Description	The median time to partial remission was not reached at Week 12. Hence, we report an estimate of the percentage of participants, estimated using Kaplan-Meier approach.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

mITT population defined as all randomized participants who took at least one dose of study drug, had at least one on-therapy evaluation and met the ASAS classification criteria for AxSpA.

Arm/Group Title	Etanercept	Placebo
Arm/Group Description:	Participants were treated with etanercept subcutaneous injection weekly plus stable background non-steroidal anti-inflammatory drug (NSAID) at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.	Participants were treated with placebo subcutaneous injection weekly plus stable background NSAID at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.
Overall Number of Participants Analyzed	105	109
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	43.3; (30.4 to 59.0)	22.3; (12.5 to 38.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 12 data only.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0022
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

8. Secondary Outcome

Title	Mean Change From Baseline in Visual Analogue Scale (VAS) Physician Global Assessments at Time Points
Description	The Investigator estimated the participant's overall disease activity over the previous 48 hours (this was independent of the Subject Assessment of Disease Activity) using a scale between 0 mm (none) and 100 mm (severe).
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description

mITT population defined as all randomized participants who took at least one dose of study drug, had at least one on-therapy evaluation and met the ASAS classification criteria for AxSpA. Missing data were imputed through LOCF approach. The values were converted to cm for analysis purposes.

Arm/Group Title	Etanercept	Placebo
Arm/Group Description:	Participants were treated with etanercept subcutaneous injection weekly plus stable background non-steroidal anti-inflammatory drug (NSAID) at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.	Participants were treated with placebo subcutaneous injection weekly plus stable background NSAID at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.
Overall Number of Participants Analyzed	102	105
Mean (Standard Error); Unit of Measure: cm
Week 2 (N = 101, 104)	-1.40 (0.24)	-0.80 (0.23)
Week 4 (N = 101, 105)	-1.91 (0.25)	-1.49 (0.24)
Week 8 (N = 101, 105)	-2.39 (0.27)	-2.10 (0.25)
Week 12 (N = 100, 105)	-2.74 (0.29)	-2.04 (0.28)
Week 16 (N = 96, 101)	-3.36 (0.23)	-2.78 (0.23)
Week 24 (N = 96, 101)	-3.66 (0.20)	-3.25 (0.23)
Week 32 (N = 96, 101)	-3.66 (0.21)	-3.38 (0.22)
Week 40 (N = 96, 101)	-3.83 (0.21)	-3.44 (0.21)
Week 48 (N = 96, 101)	-3.93 (0.23)	-3.53 (0.21)
Week 56 (N = 96, 101)	-3.98 (0.24)	-3.67 (0.22)
Week 68 (N = 96, 101)	-3.98 (0.22)	-3.60 (0.22)
Week 80 (N = 96, 101)	-4.03 (0.22)	-3.54 (0.24)
Week 92 (N = 96, 101)	-4.00 (0.22)	-3.43 (0.24)
Week 104 (N = 96, 101)	-4.12 (0.23)	-3.78 (0.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	All within group comparisons to baseline were <0.001, from paired t-test. For open-label period results include unadjusted mean changes and standard errors, no covariate adjustments were applied.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0156
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.70
	Confidence Interval	(2-Sided) 95%; -1.26 to -0.13
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 2
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0111
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.60
	Confidence Interval	(2-Sided) 95%; -1.06 to -0.14
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 4
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0936
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.42
	Confidence Interval	(2-Sided) 95%; -0.91 to 0.07
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 8
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2678
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.29
	Confidence Interval	(2-Sided) 95%; -0.81 to 0.23
	Estimation Comments	[Not Specified]

9. Secondary Outcome

Title	Mean Change From Baseline in VAS Score for Subject Assessment of Disease Activity at Time Points
Description	Participants to assess their overall disease activity over the last 48 hours using a pain scale between 0 mm (none) and 100 mm (severe), which corresponded to the magnitude of their pain.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description

mITT population defined as all randomized participants who took at least one dose of study drug, had at least one on-therapy evaluation and met the ASAS classification criteria for AxSpA. Missing data were imputed through LOCF approach. The values were converted to cm for analysis purposes.

Arm/Group Title	Etanercept	Placebo
Arm/Group Description:	Participants were treated with etanercept subcutaneous injection weekly plus stable background non-steroidal anti-inflammatory drug (NSAID) at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.	Participants were treated with placebo subcutaneous injection weekly plus stable background NSAID at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.
Overall Number of Participants Analyzed	106	109
Mean (Standard Error); Unit of Measure: cm
Week 2 (N = 105, 108)	-1.00 (0.27)	-0.08 (0.26)
Week 4 (N = 105, 109)	-1.34 (0.29)	-0.55 (0.27)
Week 8 (N = 105, 109)	-1.85 (0.32)	-1.02 (0.30)
Week 12 (N = 105, 109)	-2.06 (0.31)	-1.26 (0.30)
Week 16 (N = 100, 105)	-2.81 (0.27)	-2.65 (0.24)
Week 24 (N = 100, 105)	-2.92 (0.28)	-3.21 (0.23)
Week 32 (N = 100, 105)	-2.99 (0.27)	-3.23 (0.27)
Week 40 (N = 100, 105)	-3.38 (0.27)	-3.33 (0.25)
Week 48 (N = 100, 105)	-3.24 (0.28)	-3.36 (0.27)
Week 56 (N = 100, 105)	-3.30 (0.28)	-3.45 (0.25)
Week 68 (N = 100, 105)	-3.31 (0.28)	-3.57 (0.25)
Week 80 (N = 100, 105)	-3.10 (0.27)	-3.49 (0.25)
Week 92 (N = 100, 105)	-3.34 (0.28)	-3.65 (0.25)
Week 104 (N = 100, 105)	-3.33 (0.30)	-3.75 (0.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	All within group comparisons to baseline were <0.001, from paired t-test. For open-label period results included unadjusted mean changes and standard errors, no covariate adjustments were applied.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0102
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.80
	Confidence Interval	(2-Sided) 95%; -1.40 to -0.19
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 2
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0007
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.92
	Confidence Interval	(2-Sided) 95%; -1.44 to -0.39
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 4
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0057
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.79
	Confidence Interval	(2-Sided) 95%; -1.35 to -0.23
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 8
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0077
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.83
	Confidence Interval	(2-Sided) 95%; -1.44 to -0.22
	Estimation Comments	[Not Specified]

10. Secondary Outcome

Title	Changes From Baseline in VAS Score for Nocturnal Back Pain at Time Points
Description	The VAS scale was used to assess the level of nocturnal pain during the past 48 hours. For this, participants marked their level of pain on a 100 mm VAS anchored by 0 for "No pain " to 100 mm for "Most Severe Pain."
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description

mITT population defined as all randomized participants who took at least one dose of study drug, had at least one on-therapy evaluation and met the ASAS classification criteria for AxSpA. Missing data were imputed through LOCF approach. The values were converted to cm for analysis purposes.

Arm/Group Title	Etanercept	Placebo
Arm/Group Description:	Participants were treated with etanercept subcutaneous injection weekly plus stable background non-steroidal anti-inflammatory drug (NSAID) at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.	Participants were treated with placebo subcutaneous injection weekly plus stable background NSAID at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.
Overall Number of Participants Analyzed	106	109
Mean (Standard Error); Unit of Measure: cm
Week 2 (N = 105, 107)	-1.10 (0.31)	-0.31 (0.29)
Week 4 (N = 105, 109)	-1.54 (0.33)	-0.71 (0.31)
Week 8 (N = 105, 109)	-2.31 (0.33)	-1.34 (0.31)
Week 12 (N = 105, 109)	-1.96 (0.36)	-1.03 (0.34)
Week 16 (N = 100, 105)	-2.97 (0.31)	-2.63 (0.26)
Week 24 (N = 100, 105)	-2.79 (0.30)	-3.25 (0.26)
Week 32 (N = 100, 105)	-2.69 (0.31)	-3.11 (0.29)
Week 40 (N = 100, 105)	-3.34 (0.31)	-3.30 (0.26)
Week 48 (N = 100, 105)	-3.22 (0.31)	-3.21 (0.27)
Week 56 (N = 100, 105)	-3.15 (0.33)	-3.40 (0.27)
Week 68 (N = 100, 105)	-3.07 (0.33)	-3.27 (0.26)
Week 80 (N = 100, 105)	-3.01 (0.31)	-3.32 (0.27)
Week 92 (N = 100, 105)	-3.26 (0.32)	-3.43 (0.27)
Week 104 (N = 100, 105)	-3.28 (0.34)	-3.59 (0.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	All within group comparisons to baseline were <0.001, from paired t-test. For open-label period results include unadjusted mean changes and standard errors, no covariate adjustments were applied.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0091
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.93
	Confidence Interval	(2-Sided) 95%; -1.62 to -0.23
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 2
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0097
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.79
	Confidence Interval	(2-Sided) 95%; -1.38 to -0.19
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 4
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0101
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.82
	Confidence Interval	(2-Sided) 95%; -1.45 to -0.20
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 8
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0031
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.97
	Confidence Interval	(2-Sided) 95%; -1.61 to -0.33
	Estimation Comments	[Not Specified]

11. Secondary Outcome

Title	Changes From Baseline in VAS Score for Total Back Pain at Time Points
Description	The VAS scale was used to assess the level of total back pain during the past 48 hours. For this, participants marked their level of pain on a 100 mm VAS anchored by 0 for "No pain " to 100 mm for "Most Severe Pain."
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description

mITT population defined as all randomized participants who took at least one dose of study drug, had at least one on-therapy evaluation and met the ASAS classification criteria for AxSpA. Missing data were imputed through LOCF approach. The values were converted to cm for analysis purposes.

Arm/Group Title	Etanercept	Placebo
Arm/Group Description:	Participants were treated with etanercept subcutaneous injection weekly plus stable background non-steroidal anti-inflammatory drug (NSAID) at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.	Participants were treated with placebo subcutaneous injection weekly plus stable background NSAID at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.
Overall Number of Participants Analyzed	106	109
Mean (Standard Error); Unit of Measure: cm
Week 2 (N = 105, 107)	-0.95 (0.29)	-0.37 (0.27)
Week 4 (N = 105, 109)	-1.52 (0.31)	-0.88 (0.29)
Week 8 (N = 105, 109)	-2.19 (0.33)	-1.18 (0.31)
Week 12 (n = 105, 109)	-2.32 (0.28)	-1.39 (0.21)
Week 16 (n = 100, 105)	-2.73 (0.29)	-2.64 (0.25)
Week 24 (n = 100, 105)	-2.76 (0.28)	-2.92 (0.24)
Week 32 (n = 100, 105)	-2.58 (0.29)	-2.87 (0.26)
Week 40 (n = 100, 105)	-3.30 (0.28)	-3.20 (0.24)
Week 48 (n = 100, 105)	-3.09 (0.29)	-3.14 (0.25)
Week 56 (n = 100, 105)	-3.10 (0.29)	-3.17 (0.26)
Week 68 (n = 100, 105)	-3.02 (0.31)	-3.23 (0.26)
Week 80 (n = 100, 105)	-2.95 (0.29)	-3.17 (0.26)
Week 92 (n = 100, 105)	-3.30 (0.29)	-3.33 (0.27)
Week 104 (n = 100, 105)	-3.22 (0.32)	-3.47 (0.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	All within group comparisons to baseline were <0.001, from paired t-test. For open-label period results include unadjusted mean changes and standard errors, no covariate adjustments were applied.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0064
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.87
	Confidence Interval	(2-Sided) 95%; -1.49 to -0.25
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 2
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0407
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.57
	Confidence Interval	(2-Sided) 95%; -1.12 to -0.02
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 4
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0349
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.64
	Confidence Interval	(2-Sided) 95%; -1.24 to -0.05
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 8
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0021
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.01
	Confidence Interval	(2-Sided) 95%; -1.65 to -0.37
	Estimation Comments	[Not Specified]

12. Secondary Outcome

Title	Changes From Baseline in the Bath Ankylosing Spondylitis Functional Index (BASFI) Total Score at Time Points
Description	BASFI is a validated self assessment tool that determines the degree of functional limitation in AS. Utilizing a VAS of 0-10 (0 = easy, 10 = impossible), participants answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description

mITT population defined as all randomized participants who took at least one dose of study drug, had at least one on-therapy evaluation and met the ASAS classification criteria for AxSpA. Missing data were imputed through LOCF approach.

Arm/Group Title	Etanercept	Placebo
Arm/Group Description:	Participants were treated with etanercept subcutaneous injection weekly plus stable background non-steroidal anti-inflammatory drug (NSAID) at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.	Participants were treated with placebo subcutaneous injection weekly plus stable background NSAID at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.
Overall Number of Participants Analyzed	106	109
Mean (Standard Error); Unit of Measure: Units on a scale
Week 2 (N = 105, 107)	-0.82 (0.21)	-0.27 (0.20)
Week 4 (N = 105, 108)	-0.99 (0.22)	-0.44 (0.21)
Week 8 (N = 105, 108)	-1.28 (0.23)	-0.73 (0.22)
Week 12 (N = 105, 109)	-1.41 (0.24)	-0.84 (0.23)
Week 16 (N = 100, 105)	-1.78 (0.23)	-1.75 (0.19)
Week 24 (N = 100, 105)	-1.89 (0.22)	-1.85 (0.20)
Week 32 (N = 100, 105)	-1.81 (0.22)	-1.98 (0.21)
Week 40 (N = 100, 105)	-2.19 (0.23)	-2.13 (0.21)
Week 48 (N = 100, 105)	-2.19 (0.23)	-2.10 (0.22)
Week 56 (N = 100, 105)	-2.15 (0.22)	-2.30 (0.21)
Week 68 (N = 100, 105)	-2.21 (0.21)	-2.31 (0.22)
Week 80 (N = 100, 105)	-2.23 (0.21)	-2.19 (0.22)
Week 92 (N = 100, 105)	-2.31 (0.23)	-2.35 (0.22)
Week 104 (N = 100, 105)	-2.40 (0.23)	-2.36 (0.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	All within group comparisons to baseline were <0.001, from paired t-test. For open-label period results include unadjusted mean changes and standard errors, no covariate adjustments were applied.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0164
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.57
	Confidence Interval	(2-Sided) 95%; -1.04 to -0.11
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 2
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0095
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.54
	Confidence Interval	(2-Sided) 95%; -0.95 to -0.13
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 4
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0127
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.55
	Confidence Interval	(2-Sided) 95%; -0.99 to -0.12
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 8
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0166
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.55
	Confidence Interval	(2-Sided) 95%; -0.99 to -0.10
	Estimation Comments	[Not Specified]

13. Secondary Outcome

Title	Mean Change From Baseline in BASFI Full Day Activities at Time Points
Description	BASFI is a validated self assessment tool that determines the degree of functional limitation in AS. Utilizing a VAS of 0-10 (0 = easy, 10 = impossible), participants answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description

mITT population defined as all randomized participants who took at least one dose of study drug, had at least one on-therapy evaluation and met the ASAS classification criteria for AxSpA. Missing data were imputed through LOCF approach.

Arm/Group Title	Etanercept	Placebo
Arm/Group Description:	Participants were treated with etanercept subcutaneous injection weekly plus stable background non-steroidal anti-inflammatory drug (NSAID) at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.	Participants were treated with placebo subcutaneous injection weekly plus stable background NSAID at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.
Overall Number of Participants Analyzed	106	109
Mean (Standard Error); Unit of Measure: Units on a scale
Week 2 (N= 104, 107)	-0.99 (0.26)	-0.21 (0.25)
Week 4 (N= 104, 108)	-1.37 (0.28)	-0.70 (0.26)
Week 8 (N= 104, 108)	-1.80 (0.27)	-1.05 (0.26)
Week 12 (N = 104, 108)	-2.11 (0.29)	-1.16 (0.27)
Week 16 (N = 99, 105)	-2.37 (0.25)	-2.03 (0.24)
Week 24 (N = 99, 105)	-2.42 (0.25)	-2.13 (0.25)
Week 32 (N = 99, 105)	-2.43 (0.23)	-2.38 (0.25)
Week 40 (N = 99, 105)	-2.93 (0.26)	-2.30 (0.25)
Week 48 (N = 99, 105)	-2.73 (0.25)	-2.34 (0.27)
Week 56 (N = 99, 105)	-2.66 (0.25)	-2.59 (0.26)
Week 68 (N = 99, 105)	-2.82 (0.25)	-2.71 (0.27)
Week 80 (N = 99, 105)	-2.75 (0.25)	-2.58 (0.27)
Week 92 (N = 99, 105)	-2.93 (0.27)	-2.70 (0.27)
Week 104 (N = 99, 105)	-3.04 (0.27)	-2.66 (0.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	All within group comparisons to baseline were <0.001, from paired t-test. For open-label period results include unadjusted mean changes and standard errors, no covariate adjustments were applied.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 2
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0029
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.78
	Confidence Interval	(2-Sided) 95%; -1.28 to -0.27
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 4
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0147
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.67
	Confidence Interval	(2-Sided) 95%; -1.21 to -0.13
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 8
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0056
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.75
	Confidence Interval	(2-Sided) 95%; -1.28 to -0.22
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0010
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.95
	Confidence Interval	(2-Sided) 95%; -1.52 to -0.39
	Estimation Comments	[Not Specified]

14. Secondary Outcome

Title	Mean Change From Baseline in BASFI Bending Forward at Time Points
Description	BASFI is a validated self assessment tool that determines the degree of functional limitation in AS. Utilizing a VAS of 0-10 (0 = easy, 10 = impossible), participants answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description

mITT population defined as all randomized participants who took at least one dose of study drug, had at least one on-therapy evaluation and met the ASAS classification criteria for AxSpA. Missing data were imputed through LOCF approach.

Arm/Group Title	Etanercept	Placebo
Arm/Group Description:	Participants were treated with etanercept subcutaneous injection weekly plus stable background non-steroidal anti-inflammatory drug (NSAID) at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.	Participants were treated with placebo subcutaneous injection weekly plus stable background NSAID at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.
Overall Number of Participants Analyzed	106	109
Mean (Standard Error); Unit of Measure: Units on a scale
Week 2 (N= 105, 107)	-1.05 (0.28)	-0.40 (0.26)
Week 4 (N= 105, 108)	-0.96 (0.29)	-0.56 (0.28)
Week 8 (N= 105, 108)	-1.34 (0.29)	-0.65 (0.27)
Week 12 (N = 105, 109)	-1.34 (0.29)	-0.85 (0.27)
Week 16 (N = 100, 105)	-1.76 (0.28)	-1.57 (0.21)
Week 24 (N = 100, 105)	-2.00 (0.29)	-1.64 (0.23)
Week 32 (N = 100, 105)	-1.78 (0.28)	-1.69 (0.23)
Week 40 (N = 100, 105)	-2.12 (0.29)	-1.82 (0.24)
Week 48 (N = 100, 105)	-2.17 (0.29)	-1.83 (0.25)
Week 56 (N = 100, 105)	-2.13 (0.28)	-2.09 (0.25)
Week 68 (N = 100, 105)	-2.15 (0.27)	-1.92 (0.25)
Week 80 (N = 100, 105)	-2.18 (0.28)	-1.99 (0.26)
Week 92 (N = 100, 105)	-2.33 (0.30)	-2.04 (0.26)
Week 104 (N = 100, 105)	-2.37 (0.31)	-2.16 (0.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	All within group comparisons to baseline were <0.001, from paired t-test. For open-label period results include unadjusted mean changes and standard errors, no covariate adjustments were applied.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 2
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0173
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.65
	Confidence Interval	(2-Sided) 95%; -1.19 to -0.12
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 4
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1618
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 95%; -0.97 to 0.16
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 8
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0153
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.69
	Confidence Interval	(2-Sided) 95%; -1.25 to -0.13
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0866
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.49
	Confidence Interval	(2-Sided) 95%; -1.05 to 0.07
	Estimation Comments	[Not Specified]

15. Secondary Outcome

Title	Mean Change From Baseline in BASFI Getting Out of an Arm-less Chair at Time Points
Description	BASFI is a validated self assessment tool that determines the degree of functional limitation in AS. Utilizing a VAS of 0-10 (0 = easy, 10 = impossible), participants answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description

mITT population defined as all randomized participants who took at least one dose of study drug, had at least one on-therapy evaluation and met the ASAS classification criteria for AxSpA. Missing data were imputed through LOCF approach.

Arm/Group Title	Etanercept	Placebo
Arm/Group Description:	Participants were treated with etanercept subcutaneous injection weekly plus stable background non-steroidal anti-inflammatory drug (NSAID) at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.	Participants were treated with placebo subcutaneous injection weekly plus stable background NSAID at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.
Overall Number of Participants Analyzed	106	109
Mean (Standard Error); Unit of Measure: Units on a scale
Week 2 (N= 105, 107)	-0.94 (0.28)	-0.53 (0.27)
Week 4 (N= 105, 108)	-1.44 (0.28)	-0.84 (0.27)
Week 8 (N= 105, 108)	-1.54 (0.29)	-1.02 (0.27)
Week 12 (N = 105, 108)	-1.79 (0.28)	-1.07 (0.27)
Week 16 (N = 100, 105)	-2.04 (0.29)	-1.90 (0.23)
Week 24 (N = 100, 105)	-2.20 (0.29)	-2.12 (0.23)
Week 32 (N = 100, 105)	-2.04 (0.29)	-2.18 (0.25)
Week 40 (N = 100, 105)	-2.40 (0.30)	-2.38 (0.25)
Week 48 (N = 100, 105)	-2.40 (0.29)	-2.25 (0.26)
Week 56 (N = 100, 105)	-2.27 (0.28)	-2.47 (0.25)
Week 68 (N = 100, 105)	-2.45 (0.28)	-2.46 (0.25)
Week 80 (N = 100, 105)	-2.52 (0.28)	-2.33 (0.25)
Week 92 (N = 100, 105)	-2.60 (0.29)	-2.48 (0.25)
Week 104 (N = 100, 105)	-2.65 (0.29)	-2.48 (0.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	All within group comparisons to baseline were <0.001, from paired t-test. For open-label period results include unadjusted mean changes and standard errors, no covariate adjustments were applied.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 2
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1413
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.41
	Confidence Interval	(2-Sided) 95%; -0.95 to 0.14
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 4
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0284
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.60
	Confidence Interval	(2-Sided) 95%; -1.14 to -0.06
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 8
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0659
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.52
	Confidence Interval	(2-Sided) 95%; -1.07 to 0.03
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0098
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.72
	Confidence Interval	(2-Sided) 95%; -1.26 to -0.18
	Estimation Comments	[Not Specified]

16. Secondary Outcome

Title	Mean Change From Baseline in BASFI Physically Demanding Activities at Time Points
Description	BASFI is a validated self assessment tool that determines the degree of functional limitation in AS. Utilizing a VAS of 0-10 (0 = easy, 10 = impossible), participants answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description

mITT population defined as all randomized participants who took at least one dose of study drug, had at least one on-therapy evaluation and met the ASAS classification criteria for AxSpA. Missing data were imputed through LOCF approach.

Arm/Group Title	Etanercept	Placebo
Arm/Group Description:	Participants were treated with etanercept subcutaneous injection weekly plus stable background non-steroidal anti-inflammatory drug (NSAID) at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.	Participants were treated with placebo subcutaneous injection weekly plus stable background NSAID at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.
Overall Number of Participants Analyzed	106	109
Mean (Standard Error); Unit of Measure: Units on a scale
Week 2 (N= 104, 107)	-0.88 (0.26)	-0.13 (0.25)
Week 4 (N= 104, 108)	-1.06 (0.28)	-0.26 (0.27)
Week 8 (N= 104, 108)	-1.51 (0.28)	-0.80 (0.26)
Week 12 (N = 104, 109)	-1.69 (0.29)	-0.91 (0.27)
Week 16 (N = 99, 105)	-2.12 (0.26)	-1.79 (0.25)
Week 24 (N = 99, 105)	-2.23 (0.26)	-2.05 (0.26)
Week 32 (N = 99, 105)	-2.20 (0.25)	-2.19 (0.24)
Week 40 (N = 99, 105)	-2.79 (0.26)	-2.24 (0.27)
Week 48 (N = 99, 105)	-2.71 (0.27)	-2.25 (0.26)
Week 56 (N = 99, 105)	-2.66 (0.27)	-2.37 (0.28)
Week 68 (N = 99, 105)	-2.67 (0.26)	-2.60 (0.29)
Week 80 (N = 99, 105)	-2.70 (0.26)	-2.39 (0.28)
Week 92 (N = 99, 105)	-2.91 (0.27)	-2.59 (0.28)
Week 104 (N = 99, 105)	-3.02 (0.27)	-2.59 (0.30)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	All within group comparisons to baseline were <0.001, from paired t-test. For open-label period results include unadjusted mean changes and standard errors, no covariate adjustments were applied.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 2
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0037
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.75
	Confidence Interval	(2-Sided) 95%; -1.26 to -0.25
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 4
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0044
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.80
	Confidence Interval	(2-Sided) 95%; -1.35 to -0.25
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 8
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0104
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.71
	Confidence Interval	(2-Sided) 95%; -1.26 to -0.17
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0060
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.78
	Confidence Interval	(2-Sided) 95%; -1.33 to -0.22
	Estimation Comments	[Not Specified]

17. Secondary Outcome

Title	Mean Change From Baseline in BASFI Reaching up High at Time Points
Description	BASFI is a validated self assessment tool that determines the degree of functional limitation in AS. Utilizing a VAS of 0-10 (0 = easy, 10 = impossible), participants answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description

mITT population defined as all randomized participants who took at least one dose of study drug, had at least one on-therapy evaluation and met the ASAS classification criteria for AxSpA. Missing data were imputed through LOCF approach.

Arm/Group Title	Etanercept	Placebo
Arm/Group Description:	Participants were treated with etanercept subcutaneous injection weekly plus stable background non-steroidal anti-inflammatory drug (NSAID) at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.	Participants were treated with placebo subcutaneous injection weekly plus stable background NSAID at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.
Overall Number of Participants Analyzed	106	109
Mean (Standard Error); Unit of Measure: Units on a scale
Week 2 (N= 105, 107)	-0.33 (0.26)	-0.02 (0.24)
Week 4 (N= 105, 108)	-0.63 (0.27)	-0.21 (0.26)
Week 8 (N= 105, 108)	-0.81 (0.26)	-0.31 (0.25)
Week 12 (N = 105, 109)	-0.70 (0.27)	-0.20 (0.25)
Week 16 (N = 100, 105)	-1.09 (0.26)	-1.34 (0.22)
Week 24 (N = 100, 105)	-1.26 (0.26)	-1.46 (0.22)
Week 32 (N = 100, 105)	-1.00 (0.27)	-1.46 (0.23)
Week 40 (N = 100, 105)	-1.30 (0.25)	-1.66 (0.24)
Week 48 (N = 100, 105)	-1.38 (0.26)	-1.67 (0.25)
Week 56 (N = 100, 105)	-1.34 (0.25)	-1.76 (0.24)
Week 68 (N = 100, 105)	-1.42 (0.24)	-1.77 (0.24)
Week 80 (N = 100, 105)	-1.37 (0.24)	-1.63 (0.24)
Week 92 (N = 100, 105)	-1.55 (0.25)	-1.83 (0.24)
Week 104 (N = 100, 105)	-1.62 (0.25)	-1.76 (0.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	All within group comparisons to baseline were <0.001, from paired t-test. For open-label period results include unadjusted mean changes and standard errors, no covariate adjustments were applied.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 2
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2268
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.30
	Confidence Interval	(2-Sided) 95%; -0.80 to 0.19
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 4
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1145
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.42
	Confidence Interval	(2-Sided) 95%; -0.93 to 0.10
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 8
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0512
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.50
	Confidence Interval	(2-Sided) 95%; -1.00 to 0.00
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0509
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.51
	Confidence Interval	(2-Sided) 95%; -1.02 to 0.00
	Estimation Comments	[Not Specified]

18. Secondary Outcome

Title	Mean Change From Baseline in BASFI Climbing Steps Without Aid at Time Points
Description	BASFI is a validated self assessment tool that determines the degree of functional limitation in AS. Utilizing a VAS of 0-10 (0 = easy, 10 = impossible), participants answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description

mITT population defined as all randomized participants who took at least one dose of study drug, had at least one on-therapy evaluation and met the ASAS classification criteria for AxSpA. Missing data were imputed through LOCF approach.

Arm/Group Title	Etanercept	Placebo
Arm/Group Description:	Participants were treated with etanercept subcutaneous injection weekly plus stable background non-steroidal anti-inflammatory drug (NSAID) at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.	Participants were treated with placebo subcutaneous injection weekly plus stable background NSAID at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.
Overall Number of Participants Analyzed	106	109
Mean (Standard Error); Unit of Measure: Units on a scale
Week 2 (N= 105, 107)	-0.46 (0.26)	-0.16 (0.24)
Week 4 (N= 105, 108)	-0.65 (0.28)	-0.09 (0.26)
Week 8 (N= 105, 108)	-0.92 (0.28)	-0.44 (0.27)
Week 12 (N = 105, 109)	-0.93 (0.29)	-0.58 (0.27)
Week 16 (N = 100, 105)	-1.48 (0.28)	-1.64 (0.24)
Week 24 (N = 100, 105)	-1.54 (0.27)	-1.65 (0.25)
Week 32 (N = 100, 105)	-1.57 (0.28)	-1.97 (0.25)
Week 40 (N = 100, 105)	-1.84 (0.28)	-2.19 (0.26)
Week 48 (N = 100, 105)	-1.78 (0.28)	-2.05 (0.28)
Week 56 (N = 100, 105)	-1.81 (0.27)	-2.26 (0.26)
Week 68 (N = 100, 105)	-1.88 (0.28)	-2.34 (0.28)
Week 80 (N = 100, 105)	-1.89 (0.28)	-2.16 (0.26)
Week 92 (N = 100, 105)	-1.91 (0.29)	-2.38 (0.28)
Week 104 (N = 100, 105)	-2.01 (0.29)	-2.42 (0.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	All within group comparisons to baseline were <0.001, from paired t-test. For open-label period results include unadjusted mean changes and standard errors, no covariate adjustments were applied.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 2
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2430
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.29
	Confidence Interval	(2-Sided) 95%; -0.79 to 0.20
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 4
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0384
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.56
	Confidence Interval	(2-Sided) 95%; -1.09 to -0.03
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 8
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0797
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.48
	Confidence Interval	(2-Sided) 95%; -1.03 to 0.06
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2186
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.35
	Confidence Interval	(2-Sided) 95%; -0.90 to 0.21
	Estimation Comments	[Not Specified]

19. Secondary Outcome

Title	Mean Change From Baseline in BASFI Getting-up Off-floor From Back at Time Points
Description	BASFI is a validated self assessment tool that determines the degree of functional limitation in AS. Utilizing a VAS of 0-10 (0 = easy, 10 = impossible), participants answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description

mITT population defined as all randomized participants who took at least one dose of study drug, had at least one on-therapy evaluation and met the ASAS classification criteria for AxSpA. Missing data were imputed through LOCF approach.

Arm/Group Title	Etanercept	Placebo
Arm/Group Description:	Participants were treated with etanercept subcutaneous injection weekly plus stable background non-steroidal anti-inflammatory drug (NSAID) at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.	Participants were treated with placebo subcutaneous injection weekly plus stable background NSAID at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.
Overall Number of Participants Analyzed	106	109
Mean (Standard Error); Unit of Measure: Units on a scale
Week 2 (N= 105, 107)	-0.95 (0.28)	-0.53 (0.27)
Week 8 (N= 105, 108)	-1.10 (0.28)	-0.77 (0.27)
Week 12 (N = 105, 109)	-1.58 (0.31)	-1.18 (0.29)
Week 12 (N= 105, 108)	-1.34 (0.30)	-1.05 (0.28)
Week 16 (N = 100, 105)	-1.97 (0.28)	-2.18 (0.26)
Week 24 (N = 100, 105)	-2.07 (0.26)	-2.18 (0.25)
Week 32 (N = 100, 105)	-2.05 (0.27)	-2.31 (0.27)
Week 40 (N = 100, 105)	-2.52 (0.27)	-2.59 (0.27)
Week 48 (N = 100, 105)	-2.40 (0.28)	-2.51 (0.27)
Week 56 (N = 100, 105)	-2.48 (0.27)	-2.81 (0.27)
Week 68 (N = 100, 105)	-2.50 (0.27)	-2.75 (0.28)
Week 80 (N = 100, 105)	-2.50 (0.26)	-2.63 (0.27)
Week 92 (N = 100, 105)	-2.55 (0.29)	-2.84 (0.28)
Week 104 (N = 100, 105)	-2.71 (0.29)	-2.90 (0.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	All within group comparisons to baseline were <0.001, from paired t-test. For open-label period results include unadjusted mean changes and standard errors, no covariate adjustments were applied.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 2
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1410
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.41
	Confidence Interval	(2-Sided) 95%; -0.96 to 0.14
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 4
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2299
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.33
	Confidence Interval	(2-Sided) 95%; -0.88 to 0.21
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 8
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3221
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.29
	Confidence Interval	(2-Sided) 95%; -0.87 to 0.29
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1891
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 95%; -0.99 to 0.20
	Estimation Comments	[Not Specified]

20. Secondary Outcome

Title	Mean Change From Baseline in BASFI Standing Unsupported for 10 Minutes at Time Points
Description	BASFI is a validated self assessment tool that determines the degree of functional limitation in AS. Utilizing a VAS of 0-10 (0 = easy, 10 = impossible), participants answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description

mITT population defined as all randomized participants who took at least one dose of study drug, had at least one on-therapy evaluation and met the ASAS classification criteria for AxSpA. Missing data were imputed through LOCF approach.

Arm/Group Title	Etanercept	Placebo
Arm/Group Description:	Participants were treated with etanercept subcutaneous injection weekly plus stable background non-steroidal anti-inflammatory drug (NSAID) at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.	Participants were treated with placebo subcutaneous injection weekly plus stable background NSAID at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.
Overall Number of Participants Analyzed	106	109
Mean (Standard Error); Unit of Measure: Units on a scale
Week 2 (N= 105, 107)	-0.58 (0.26)	-0.17 (0.24)
Week 4 (N= 105, 108)	-0.80 (0.27)	-0.25 (0.25)
Week 8 (N= 105, 108)	-1.03 (0.28)	-0.60 (0.27)
Week 12 (N = 105, 109)	-1.33 (0.30)	-0.97 (0.29)
Week 16 (N = 100, 105)	-1.88 (0.26)	-1.93 (0.23)
Week 24 (N = 100, 105)	-1.96 (0.26)	-1.98 (0.25)
Week 32 (N = 100, 105)	-1.84 (0.26)	-2.19 (0.25)
Week 40 (N = 100, 105)	-2.17 (0.27)	-2.44 (0.26)
Week 48 (N = 100, 105)	-2.30 (0.28)	-2.41 (0.28)
Week 56 (N = 100, 105)	-2.26 (0.25)	-2.63 (0.26)
Week 68 (N = 100, 105)	-2.37 (0.27)	-2.64 (0.27)
Week 80 (N = 100, 105)	-2.41 (0.26)	-2.56 (0.26)
Week 92 (N = 100, 105)	-2.42 (0.27)	-2.72 (0.28)
Week 104 (N = 100, 105)	-2.53 (0.27)	-2.74 (0.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	All within group comparisons to baseline were <0.001, from paired t-test. For open-label period results include unadjusted mean changes and standard errors, no covariate adjustments were applied.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 2
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1080
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 95%; -0.90 to 0.09
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 4
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0389
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.54
	Confidence Interval	(2-Sided) 95%; -1.06 to -0.03
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 8
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1181
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.44
	Confidence Interval	(2-Sided) 95%; -0.98 to 0.11
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2271
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.36
	Confidence Interval	(2-Sided) 95%; -0.94 to 0.22
	Estimation Comments	[Not Specified]

21. Secondary Outcome

Title	Mean Change From Baseline in BASFI Looking Over Shoulder at Time Points
Description	BASFI is a validated self assessment tool that determines the degree of functional limitation in AS. Utilizing a VAS of 0-10 (0 = easy, 10 = impossible), participants answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description

mITT population defined as all randomized participants who took at least one dose of study drug, had at least one on-therapy evaluation and met the ASAS classification criteria for AxSpA. Missing data were imputed through LOCF approach.

Arm/Group Title	Etanercept	Placebo
Arm/Group Description:	Participants were treated with etanercept subcutaneous injection weekly plus stable background non-steroidal anti-inflammatory drug (NSAID) at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.	Participants were treated with placebo subcutaneous injection weekly plus stable background NSAID at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.
Overall Number of Participants Analyzed	106	109
Mean (Standard Error); Unit of Measure: Units on a scale
Week 8 (N= 105, 108)	-1.21 (0.28)	-0.84 (0.26)
Week 12 (N = 105, 108)	-1.40 (0.28)	-0.82 (0.27)
Week 16 (N = 100, 105)	-1.63 (0.28)	-1.69 (0.26)
Week 24 (N = 100, 105)	-1.59 (0.28)	-1.84 (0.27)
Week 32 (N = 100, 105)	-1.61 (0.29)	-1.92 (0.26)
Week 40 (N = 100, 105)	-1.91 (0.28)	-2.03 (0.27)
Week 48 (N = 100, 105)	-1.97 (0.28)	-2.08 (0.27)
Week 56 (N = 100, 105)	-1.99 (0.27)	-2.27 (0.26)
Week 68 (N = 100, 105)	-2.05 (0.27)	-2.25 (0.27)
Week 80 (N = 100, 105)	-2.03 (0.27)	-1.94 (0.29)
Week 92 (N = 100, 105)	-1.97 (0.28)	-2.19 (0.27)
Week 104 (N = 100, 105)	-2.14 (0.27)	-2.16 (0.28)
Week 2 (N= 105, 107)	-0.83 (0.27)	-0.07 (0.25)
Week 4 (N= 105, 108)	-0.88 (0.28)	-0.33 (0.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	All within group comparisons to baseline were <0.001, from paired t-test. For open-label period results include unadjusted mean changes and standard errors, no covariate adjustments were applied.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 2
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0044
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.75
	Confidence Interval	(2-Sided) 95%; -1.27 to -0.24
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 4
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0455
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.55
	Confidence Interval	(2-Sided) 95%; -1.09 to -0.01
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 8
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1750
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.37
	Confidence Interval	(2-Sided) 95%; -0.91 to 0.17
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0379
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.58
	Confidence Interval	(2-Sided) 95%; -1.12 to -0.03
	Estimation Comments	[Not Specified]

22. Secondary Outcome

Title	Mean Change From Baseline in BASFI Putting on Socks at Time Points
Description	BASFI is a validated self assessment tool that determines the degree of functional limitation in AS. Utilizing a VAS of 0-10 (0 = easy, 10 = impossible), participants answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions.
Time Frame	Baseline to Week 104

Outcome Measure Data

Analysis Population Description

mITT population defined as all randomized participants who took at least one dose of study drug, had at least one on-therapy evaluation and met the ASAS classification criteria for AxSpA. Missing data were imputed through LOCF approach.

Arm/Group Title	Etanercept	Placebo
Arm/Group Description:	Participants were treated with etanercept subcutaneous injection weekly plus stable background non-steroidal anti-inflammatory drug (NSAID) at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.	Participants were treated with placebo subcutaneous injection weekly plus stable background NSAID at optimal anti-inflammatory dose for 12 weeks (double-blind period). All participants who completed the 12-week double-blind period entered into a 92 week open-label period and received etanercept 50 mg once weekly and background NSAID.
Overall Number of Participants Analyzed	106	109
Mean (Standard Error); Unit of Measure: Units on a scale
Week 2 (N= 105, 107)	-0.94 (0.27)	-0.47 (0.26)
Week 4 (N= 105, 108)	-0.74 (0.29)	-0.34 (0.27)
Week 8 (N= 105, 108)	-1.04 (0.28)	-0.54 (0.27)
Week 12 (N = 105, 108)	-1.02 (0.28)	-0.57 (0.26)
Week 16 (N = 100, 105)	-1.52 (0.29)	-1.36 (0.21)
Week 24 (N = 100, 105)	-1.65 (0.29)	-1.44 (0.21)
Week 32 (N = 100, 105)	-1.55 (0.29)	-1.49 (0.21)
Week 40 (N = 100, 105)	-1.92 (0.28)	-1.64 (0.23)
Week 48 (N = 100, 105)	-1.95 (0.28)	-1.60 (0.23)
Week 56 (N = 100, 105)	-1.85 (0.29)	-1.75 (0.21)
Week 68 (N = 100, 105)	-1.80 (0.27)	-1.62 (0.22)
Week 80 (N = 100, 105)	-1.92 (0.29)	-1.66 (0.22)
Week 92 (N = 100, 105)	-1.93 (0.29)	-1.70 (0.22)
Week 104 (N = 100, 105)	-1.95 (0.29)	-1.71 (0.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	All within group comparisons to baseline were <0.001, from paired t-test. For open-label period results include unadjusted mean changes and standard errors, no covariate adjustments were applied.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 2
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0826
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.46
	Confidence Interval	(2-Sided) 95%; -0.98 to 0.06
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 4
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1538
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 95%; -0.96 to 0.15
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Etanercept, Placebo
	Comments	Secondary and supportive analyses were performed at 2-sided alpha = 0.05 significance level. No adjustment for multiple testing was made. Comparative analysis was carried out for Week 2, 4, 8, 12 data only. Week 8
	Type of Statistical Test	Superiority or Other
	Comments