Study Evaluating Etanercept for the Treatment of Active, Severe, and Advanced Axial Ankylosing Spondylitis

A Multicentre, Double-Blind, Placebo-Controlled, Randomised Study of Etanercept in the Treatment of Adult Patients With Active, Severe, and Advanced Axial Ankylosing Spondylitis

Evaluation of the efficacy and safety of etanercept (Enbrel) in patients with active, severe and advanced ankylosing spondylitis.

Study Overview

• Status: Completed
• Conditions: Ankylosing Spondylitis
• Intervention / Treatment: Other: Placebo; Drug: Etanercept (Enbrel)

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Amiens, France, 80094
  • Arles, France, 13200
  • Avignon, France, 84000
  • Bordeaux, France, 33076
  • Cabestany, France, 66330
  • Corbeil Essonnes, France, 91100
  • Montpellier, France, 34295
  • Nice, France, 6202
  • Orleans, France, 45032
  • Paris (Ambroise Pare), France, 92401
  • Paris (Bichat), France, 75018
  • Paris (COCHIN), France, 75679
  • Paris (Pitie Salpetriere), France, 75651
  • Paris (Saint Antoine), France, 75571
  • Strasbourg, France, 67098
  • Toulouse, France, 31000
• Germany
  • Berlin, Germany, 12200
  • Herne, Germany, 446652
• Hungary
  • Budapest, Hungary, 1023
  • Debrecen, Hungary, 4004
• Netherlands
  • Maastricht, Netherlands, 6229 HX

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

• Active and severe ankylosing spondylitis
• Ankylosing spondylitis refractory to standard anti-rheumatic treatment
• Between 18 and 70 years of age

Exclusion criteria

• Prior exposure to any TNF-inhibitor, including etanercept
• DMARDs (other than hydroxychloroquine, methotrexate and sulphasalazine) within 4 weeks of study drug initiation
• Dose of NSAIDs changed within two weeks of study drug initiation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A	Drug: Etanercept (Enbrel); 50 mg injection once weekly
Placebo Comparator: B	Other: Placebo; placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Normalized Net Incremental Area Under the Curve (AUC) for the Bath Ankylosing Spondylitis Disease Activities Index (BASDAI) Between Randomization and Week 12	BASDAI subject asessment of discomfort, pain and fatigue measured using a 100 millimeter Visual Analog Scale; range: 0=none to 100=very severe. Normalized net incremental area under the curve (AUC) = area between baseline and the BASDAI curve as a function of time (randomization to Week 12); computed using the linear trapezoidal method. All areas above baseline and under the curve are positive and all areas below baseline and above the curve are negative. Net incremental AUC = sum of these areas; this result was then divided by the study duration of the patients; negative value = improvement.	Baseline, Week 2, Week 4, Week 8, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Subjects Achieving Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response	BASDAI subject assessment of discomfort, pain and fatigue was measured using a 100 millimeter Visual Analog Scale (VAS); range: 0=none to 100=very severe. BASDAI 50 response defined as at least a 50 percent (%) improvement (decrease) from baseline to observation (last observation carried forward) in the BASDAI. Baseline score minus score at observation divided by Baseline score * 100 = >=50%.	Baseline, Week 2, Week 4, Week 8, Week 12
Percent of Subjects Achieving Assessment Ankylosing Spondylitis (ASAS) 20 at Weeks 2, 4, 8, 12	ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) patients; 4 domains: patient global assessment of disease activity, pain, function,and inflammation. ASAS 20 = 20% improvement (versus baseline) and an absolute change (net improvement) ≥ 10 millimeters (mm) on a 0-100 mm scale (100=high disease activity) for ≥ 3 domains, and no worsening (absence of deterioration by >=20% and by >= 10 mm) in remaining domain.	Week 2, Week 4, Week 8, Week 12
Percent of Subjects Acheiving Assessment Ankylosing Spondylitis (ASAS) 20 at Weeks 14, 18, 24	ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) patients; 4 domains: patient global assessment of disease activity, pain, function, and inflammation. ASAS 20 = 20% improvement (versus baseline) and an absolute change (net improvement) ≥ 10 units (millimeters) on a 0-100 scale (100=high disease activity) for ≥ 3 domains, and no worsening (absence of deterioration by >=20% and by >=10 mm) in remaining domain.	Week 14, Week 18, Week 24
Percent of Subjects Achieving Assessment Ankylosing Spondylitis (ASAS) 50 at Weeks 2, 4, 8, 12	ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) patients; 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 50 = 50% improvement (versus baseline) and an absolute (net) change ≥ 20 units on a 0-100 scale (high disease activity) for ≥ 3 domains, and no worsening (absence of deterioration by >=20% and by >=10 mm) in remaining domain.	Week 2, Week 4, Week 8, Week 12
Percent of Subjects Achieving Assessment Ankylosing Spondylitis (ASAS) 50 at Weeks 14, 18, 24	ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) patients; 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 50 = 50% improvement (vs. baseline) and an absolute (net) change ≥ 20 units on a 0-100 scale (high disease activity) for ≥ 3 domains, and no worsening (absence of deterioration by >=20% and by >=10 mm) in remaining domain.	Week 14, Week 18, Week 24
Percent of Subjects Achieving Assessment Ankylosing Spondylitis (ASAS) 70 at Weeks 2, 4, 8, 12	ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) patients; 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 70 = 70% improvement (vs. baseline) and an absolute change ≥ 20 units on a 0-100 scale (high disease activity) for ≥ 3 domains, and no worsening (absence of deterioration by >=20% and by >= 10 mm) in remaining domain.	Week 2, Week 4, Week 8, Week 12
Percent of Subjects Achieiving Assessment Ankylosing Spondylitis (ASAS) 70 at Weeks 14, 18, 24	ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) patients; 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 70 = 70% improvement (vs. baseline) and an absolute change ≥ 20 units on a 0-100 scale (high disease activity) for ≥ 3 domains, and no worsening (absence of deterioration by >=20% and by >= 10 mm) in remaining domain.	Week 14, Week 18, Week 24
Percent of Subjects Achieving Partial Remission at Weeks 2, 4, 8, 12	Partial remission defined as a score of <20 millimeters (mm) on a scale of 0 to 100 mm in each of 4 domains: Visual Analog Scale (VAS) patient global assessment, VAS pain score (Total Back Pain), Bath Ankylosing Spondylitis Functional Index (BASFI) score, and Bath Ankylosing Spondylitis Disease Activities Index (BASDAI)-mean of two morning stiffness-related VAS scores. A negative score indicates an improvement in disease activity and a positive score indicates worsening.	Week 2, Week 4, Week 8, Week 12
Percent of Subjects Achieving Partial Remission at Weeks 14, 18, 24	Partial remission defined as a score of <20 millimeters (mm) on a scale of 0 to 100 mm in each of 4 domains: Visual Analog Scale (VAS) patient global assessment, VAS pain score (Total Back Pain), Bath Ankylosing Spondylitis Functional Index (BASFI) score, and Bath Ankylosing Spondylitis Disease Activities Index (BASDAI)-mean of two morning stiffness-related VAS scores. A negative score indicates an improvement in disease activity and a positive score indicates worsening.	Week 14, Week 18, Week 24
Normalized Net Incremental Area Under the Curve (AUC) for Patient Global Assessment (PGA) Between Baseline and Week 12	PGA was measured using a 100 millimeter Visual Analog Scale (VAS) ranging from 0 = very good to 100 = very bad. Normalized net incremental area under the curve (AUC)=area between baseline and the Patient Global Asessment curve as a function of time (randomization to Week 12); computed using the linear trapezoidal method. All areas above baseline and under the curve are positive and all area below baseline and above the curve are negative. Net incremental AUC = sum of these areas; this result was then divided by the study duration of the patients; negative value = improvement.	Baseline, Week 2, Week 4, Week 8, Week 12
Change From Baseline in Patient Global Assessment Visual Analog Scale (VAS) at Weeks 2, 4, 8, 12	Patient global assessment of all the ways ankylosing spondylitis affected them in the last 48 hours using a 100 millimeter (mm) Visual Analog Scale (VAS); range 0=very good to 100=very bad.	Baseline, Week 2, Week 4, Week 8, Week 12
Change From Baseline in Patient Global Assessment at Weeks 14, 18, 24	Patient global assessment of all the ways ankylosing spondylitis affected them in the last 48 hours using a 100 millimeter (mm) Visual Analog Scale (VAS); range 0=very good to 100=very bad.	Week 14, Week 18, Week 24
Normalized Net Incremental Area Under the Curve (AUC) for Physician Global Assessment (PGA) Between Baseline and Week 12	PGA was measured using a 100 millimeter Visual Analog Scale (VAS) ranging from 0 = very good to 100 = very bad. Normalized net incremental area under the curve (AUC) = area between baseline and the Physician Global Assessment curve as a function of time (randomization to Week 12); computed using the linear trapezoidal method. All areas above baseline and under the curve are positive and all area below baseline and above the curve are negative. Net incremental AUC = sum of these areas; this result was then divided by the study duration of the patients; negative value = improvement.	Baseline, Week 2, Week 4, Week 8, Week 12
Change From Baseline in Physician Global Assessment Visual Analog Scale at Weeks 2, 4, 8, 12	Physician global assessment of all the ways ankylosing spondylitis has affected patient during the last 48 hours. 100 millimeter (mm) Visual Analog Scale (VAS); range: 0=very good to 100=very bad.	Baseline, Week 2, Week 4, Week 8, Week 12
Change From Baseline in Physician Global Assessment at Weeks 14, 18, 24	Physician global assessment of all the ways ankylosing spondylitis has affected patient during the last 48 hours. 100 millimeter (mm) Visual Analog Scale (VAS); range: 0=very good to 100=very bad.	Week 14, Week 18, Week 24
Normalized Net Incremental Area Under the Curve (AUC) for Nocturnal Back Pain Between Baseline and Week 12	Nocturnal back pain was measured using a 100 millimeter Visual Analog Scale (VAS); range: 0 = none to 100 = extreme. Normalized net incremental area under the curve (AUC) = area between baseline and the Nocturnal Back Pain curve as a function of time (randomization to Week 12); computed using the linear trapezoidal method. All areas above baseline and under the curve are positive and all area below baseline and above the curve are negative. Net incremental AUC = sum of these areas; this result was then divided by the study duration of the patients; negative value = improvement.	Baseline, Week 2, Week 4, Week 8, Week 12
Change From Baseline in Nocturnal Back Pain at Weeks 2, 4, 8, 12	Subject assessment of nocturnal back pain due to ankylosing spondylitis during the last 48 hours using a 100 millimeter (mm) Visual Analog Scale (VAS); range: 0=none to 100=extreme.	Baseline, Week 2, Week 4, Week 8, Week 12
Change From Baseline in Nocturnal Back Pain at Weeks 14, 18, 24	Subject assessment of nocturnal back pain due to ankylosing spondylitis during the last 48 hours using a 100 millimeter (mm) Visual Analog Scale (VAS); range: 0=none to 100=extreme.	Week 14, Week 18, Week 24
Normalized Net Incremental Area Under the Curve (AUC) for Total Back Pain Between Baseline and Week 12	Total back pain was measured using a 100 millimeter Visual Analog Scale (VAS); range: 0 = none to 100 = extreme. Normalized net incremental area under the curve (AUC) = area between baseline and the Total Back Pain curve as a function of time (randomization to Week 12); computed using the linear trapezoidal method. All areas above baseline and under the curve are positive and all area below baseline and above the curve are negative. Net incremental AUC = sum of these areas; this result was then divided by the study duration of the patients; negative value = improvement.	Baseline, Week 2, Week 4, Week 8, Week 12
Change From Baseline in Total Back Pain at Weeks 2, 4, 8, 12	Subject assessment of total back pain due to ankylosing spondylitis during the last 48 hours using a 100 millimeter (mm) Visual Analog Scale (VAS); range: 0=none to 100=extreme.	Baseline, Week 2, Week 4, Week 8, Week 12
Change From Baseline in Total Back Pain at Weeks 14, 18, 24	Subject assessment of total back pain due to ankylosing spondylitis during the last 48 hours using a 100 millimeter Visual Analog Scale (VAS); range: 0=none to 100=extreme.	Week 14, Week 18, Week 24
Normalized Net Incremental Area Under the Curve (AUC) for the Bath Ankylosing Spondylitis Functional Index (BASFI) Between Baseline and Week 12	BASFI was measured using a 100 millimeter Visual Analog Scale (VAS) ranging from 0 = easy to 100 = impossible. Normalized net incremental area under the curve (AUC) = area between baseline and the BASFI curve as a function of time (randomization to Week 12); computed using the linear trapezoidal method. All areas above baseline and under the curve are positive and all area below baseline and above the curve are negative. Net incremental AUC = sum of these areas; this result was then divided by the study duration of the patients; negative value = improvement.	Baseline, Week 2, Week 4, Week 8, Week 12
Change From Baseline in the Bath Ankylosing Spondylitis Functional Index (BASFI) at Weeks 2, 4, 8, 12	BASFI is a validated self assessment tool that determines the degree of functional limitation in ankylosing spondylitis (AS) patients using a 100 millimeter (mm) Visual Analog Scale (VAS) measuring level of ability with activities in the last 48 hours; range: 0=easy to 100=impossible. Higher score = greater limitation.	Baseline, Week 2, Week 4, Week 8, Week 12
Bath Ankylosing Functional Index (BASFI): Independent Components at Weeks 2, 4, 8, 12	Subject rating of last 48 hours, 100 millimeter Visual Analog Scale; range 0=easy to 100=impossible: 1)Putting on socks/tights without (w/o) help; 2)Bending forward from waist to pickup pen from floor w/o aid; 3)Reaching to high shelf w/o aid; 4)Getting out of armless dining room chair w/o using hands/other help; 5)Getting up off floor w/o help from lying on back; 6)Standing unsupported 10 minutes w/o discomfort; 7)Climbing 12-15 steps w/o handrail or walking aid; 8)Looking over shoulder w/o turning body; 9) Doing physically demanding activities; 10) Doing full days activities (home or work).	Baseline, Week 2, Week 4, Week 8, Week 12
Bath Ankylosing Functional Index (BASFI) Independent Components at Weeks 14, 18, 24	Subject rating of last 48 hours, 100 mm Visual Analog Scale; range 0=easy to 100=impossible: 1) Putting on socks/tights without (w/o) help; 2) Bending forward from waist to pickup pen from floor w/o aid; 3) Reaching to high shelf w/o aid; 4) Getting out of armless dining room chair w/o using hands/other help; 5) Getting up off floor w/o help from lying on back; 6) Standing unsupported 10 minutes w/o discomfort; 7) Climbing 12-15 steps w/o handrail or walking aid; 8) Looking over shoulder w/o turning body; 9) Doing physically demanding activities; 10) Doing full days activities (home or work).	Week 14, Week 18, Week 24
Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Weeks 2, 4, 8, 12	BASDAI is a validated self assessment tool used to determine disease activity in patients with ankylosing spondylitis in the last 48 hours. Utilizing a Visual Analog Scale (VAS) of 0-10 (0=none and 10=very severe) patient's answered 6 questions measuring discomfort, pain and fatigue. The BASDAI final mean score was calculated taking all 6 VAS assessments.	Baseline, Week 2, Week 4, Week 8, Week 12
Change From Baseline in the Bath Ankylosing Spondylitis (AS) Disease Activity Index (BASDAI) at Weeks 14, 18, 24	BASDAI is a validated self assessment tool used to determine disease activity in patients with ankylosing spondylitis (AS) in the last 48 hours. Utilizing a Visual Analog Scale (VAS) of 0-10 (0=none and 10=very severe) patient's answered 6 questions measuring discomfort, pain and fatigue. The BASDAI final mean score was calculated taking all 6 VAS assessments.	Week 14, Week 18, Week 24
Bath Ankylosing Spondylitis (AS) Disease Activity Index (BASDAI) Independent Components at Weeks 2, 4, 8, 12	BASDAI subject rated components over last 48 hours using 100 mm Visual Analog Scale; components 1-5: range 0=none to 100=very severe; component 6: range:0=0 hours to 100=2 hours or more. 1) Overall level of fatigue/tiredness experienced; 2) Overall level of AS neck,back or hip pain experienced; 3) Overall level of pain/swelling in joints other than neck, back or hips; 4) Overall level of discomfort from any areas tender to touch or pressure; 5) Overall level of morning stiffness from time of awakening; 6) Duration of morning stiffness from time of awakening, and morning stiffness subscale.	Week 2, Week 4, Week 8, Week 12
Bath Ankylosing Spondylitis (AS) Disease Activity Index (BASDAI) Independent Components at Weeks 14, 18, 24	BASDAI subject rated components over last 48 hours using a 100 millimeter Visual Analog Scale; components 1-5: range 0=none to 100=very severe; component 6: range:0=0 hours to 100=2 hours or more. 1) Overall level of fatigue/tiredness experienced; 2) Overall level of AS neck,back or hip pain experienced; 3)Overall level of pain/swelling in joints other than neck,back or hips; 4) Overall level of discomfort from any areas tender to touch or pressure; 5) Overall level of morning stiffness from time of awakening; 6) Duration of morning stiffness from time of awakening.	Week 14, Week 18, Week 24
Normalized Net Incremental Area Under the Curve (AUC) for Bath Ankylosing Spondylitis-Global Score (BAS-G) Visual Analog Scale Between Baseline and Week 12	BAS-G was measured using a 100 millimeter Visual Analog Scale (VAS) ranging from 0=none to 100=very important. Normalized net incremental area under the curve (AUC) = area between baseline and the BAS-G curve as a function of time (randomization to Week 12); computed using the linear trapezoidal method. All areas above baseline and under the curve are positive and all area below baseline and above the curve are negative. Net incremental AUC = sum of these areas; this result was then divided by the study duration of the patients; negative value = improvement.	Baseline, Week 2, Week 4, Week 8, Week 12
Change From Baseline in the Bath Ankylosing Spondylitis-Global Score (BAS-G) at Weeks 2, 4, 8, 12	Subject assessment of the effect of their disease on well-being over last 48 hours using a 100 millimeter (mm) Visual Analog Scale (VAS); range: 0=none to 100=very important.	Baseline, Week 2, Week 4, Week 8, Week 12
Change From Baseline in the Bath Ankylosing Spondylitis-Global Score (BAS-G) at Weeks 14, 18, 24	Subject assessment of the effect of their disease on well-being over last 48 hours using a 100 millimeter Visual Analog Scale (VAS); range: 0=none to 100=very important.	Week 14, Week 18, Week 24
Bath Ankylosing Spondylitis Global Score (BAS-G) Independent Component: Effect of Disease on Well-being at Weeks 2, 4, 8, 12	Subject evaluation of the effect of their disease on well-being over the last week using a using a 100 millimeter Visual Anaog Scale; range: 0=none to 100=very important.	Baseline, Week 2, Week 4, Week 8, Week 12
Change From Baseline to Week 12 in Forced Vital Capacity (FVC), Vital Capacity (VC), and Forced Expiratory Volume in One Second (FEV1)		Baseline, Week 12
Change From Baseline to Week 12 in Ratio Forced Expitatory Volume in One Second (FEV1)/Forced Vital Capacity (FVC) (%)		Baseline, Week 12
Normalized Net Incremental Area Under the Curve (AUC) for the Bath Ankylosing Spondylitis Metrology Index (BASMI) Between Baseline and Week 12	BASMI was composed of 5 measures; each measure scored 0-2 (0=normal mobility, 2=severe reduction); final score range: 0 to 10. Normalized net incremental area under the curve (AUC) = area between baseline and the BASMI curve as a function of time (randomization to Week 12); computed using the linear trapezoidal method. All areas above baseline and under the curve are positive and all area below baseline and above the curve are negative. Net incremental AUC = sum of these areas; this result was then divided by the study duration of the patients; negative value = improvement.	Baseline, Week 2, Week 4, Week 8, Week 12
Change From Baseline in Spinal Mobility Measured With the Bath Ankylosing Spondylitis Metrology Index (BASMI) at Weeks 2, 4, 8, 12	BASMI is an objective measure of spinal mobility. The BASMI score is composed of 5 measures: cervical rotation, intermalleolar distance, modified Schober test, lateral flexion and tragus to wall distance. Each measure was scored 0-2 (0=normal mobility, 2=severe reduction) to give a final score ranging 0 to 10. Higher score = greater reduction in spinal mobility.	Week 2, Week 4, Week 8, Week 12
Change From Baseline in Spinal Mobility Measured With the Bath Ankylosing Spondylitis Metrology Index (BASMI) at Weeks 14, 18, 24	BASMI is an objective measure of spinal mobility. The BASMI score is composed of 5 measures: cervical rotation, intermalleolar distance, modified Schober's test, lateral flexion and tragus to wall distance. Each measure was scored 0-2 (0=normal mobility, 2=severe reduction) to give a final score ranging 0 to 10. Higher score = greater reduction in spinal mobility.	Week 14, Week 18, Week 24
Bath Ankylosing Spondylitis Metrology Index (BASMI) Independent Component: Cervical Rotation at Weeks 2, 4, 8, 12	Cervical rotation: measurement of degrees to which the subjects could turn their heads as far as possible to the right and then to the left. Mean of ordinal scores from 0: >= 85 degrees to 10: <= 8.5 degrees.	Baseline, Week 2, Week 4, Week 8, Week 12
Bath Ankylosing Spondylitis Metrology Index (BASMI): Spinal Mobility Measured With Cervical Rotation at Weeks 14, 18, 24	Cervical rotation: measurement in degree to which the subjects could turn their heads as far as possible to the right and then to the left. Mean of ordinal scores from 0: >= 85 degrees to 10: <= 8.5 degrees.	Week 14, Week 18, Week 24
Bath Ankylosing Spondylitis Metrology Index (BASMI) Independent Component: Spinal Mobility Measured With Tragus-to-wall Distance at Baseline and Weeks 2, 4, 8, 12	Measurement in centimeters (cm) of distance between the tragus and wall from right and left side while subject is standing with back against the wall; knees straight; scapulae, buttocks, and heels against the wall; with head in neutral position. Measurement of two attempts on right and left sides. Mean of ordinal scores from 0: <= 10 cm to 10: >= 37 cm.	Baseline, Week 2, Week 4, Week 8, Week 12
Bath Ankylosing Spondylitis Metrology Index (BASMI): Spinal Mobility Measured With Tragus-to-wall Measurement at Weeks 14, 18, 24	Measurement in centimeters (cm) of distance between the tragus and wall from right and left side while subject is standing with back against the wall; knees straight; scapulae, buttocks, and heels against the wall; with head in neutral position. Measurement of two tries on right and left sides. Mean of ordinal scores from 0: <= 10 cm to 10: >= 37 cm.	Week 14, Week 18, Week 24
Bath Ankylosing Spondylitis Metrology Index (BASMI) Independent Component: Spinal Mobility Measured With Lateral Flexion at Baseline and Weeks 2, 4, 8, and 12	Measurement in centimters (cm) of distance between subject's middle fingertip and the floor after bending sideways, without bending knees or lifting heels, while attemting to keep shoulders in same place (flexion position). Measurement of two attempts on each side (right and left). Mean of ordinal scores from 0: >=20 cm to 10: <=1.2 cm.	Baseline, Week 2, Week 4, Week 8, Week 12
Bath Ankylosing Spondylitis Metrology Index (BASMI): Spinal Mobility Measured With Lateral Flexion at Weeks 14, 18, 24	Measurement in centimters (cm) of distance between subject's middle fingertip and the floor after bending sideways, without bending knees or lifting heels, while attempting to keep shoulders in same place (flexion position). Measurement of two attempts on each side (right and left). Mean of ordinal scores from 0: >=20 cm to 10: <=1.2 cm.	Week 14, Week 18, Week 24
Bath Ankylosing Spondylitis Metrology Index (BASMI) Independent Component: Spinal Mobility Measured With Modified Schober's Test at Baseline and Weeks 2, 4, 8, 12	Measurement in centimeters of the distance between marks originally placed while the subject was standing erect 10 centimeters (cm) above and 5 cm below the midpoint of a line that joints the posterior superior iliac spines. Distance between marks was remeasured with subject maximally bend forward, knees fully extended, with spine in full flexion. Measurement of two attempts. Mean of ordinal scores from 1: 5.7 to 6.3 cm, to 10: <=0.7 cm.	Baseline, Week 2, Week 4, Week 8, Week 12
Bath Ankylosing Spondylitis Metrology Index (BASMI): Spinal Mobility Measured With Modified Schober's Test at Weeks 14, 18, 24	Measurement in centimeters of the distance between marks originally placed while the subject was standing erect 10 centimeters (cm) above and 5 cm below the midpoint of a line that joints the posterior superior iliac spines. Distance between marks was remeasured with subject maximally bend forward, knees fully extended, with spine in full flexion. Measurement of two attempts. Mean of ordinal scores from 1: 5.7 to 6.3 cm, to 10: <=0.7 cm.	Week 14, Week 18, Week 24
Bath Ankylosing Spondylitis Metrology Index (BASMI) Independent Component: Spinal Mobility Measured With Intermalleolar Distance at Baseline and Weeks 2, 4, 8, 12	Measurement in centimeters (cm) of the distance between the medial malleoli when subject is lying supine with knees and feet straight up with legs separated as far as possible. Measurement of two attempts. Mean of ordinal scores from 0: >= 120 cm, to 9: 30 to 39.9 cm.	Baseline, Week 2, Week 4, Week 8, Week 12
Bath Ankylosing Spondylitis Metrology Index (BASMI): Spinal Mobility Measured With Intermalleolar Distance at Weeks 14, 18, 24	Measurement in centimeters (cm) of the distance between the medial malleoli when subject is lying supine with knees and feet straight up with legs separated as far as possible. Measurement of two attempts. Mean of ordinal scores from 0: >= 120 cm, to 9: 30 to 39.9 cm.	Week 14, Week 18, Week 24
Normalized Net Incremental Area Under the Curve (AUC) for the Chest Expansion Test Between Baseline and Week 12	Normalized net incremental area under the curve (AUC) = area between baseline and the Chest Expansion Test curve as a function of time (randomization to Week 12); computed using the linear trapezoidal method. All areas above baseline and under the curve are positive and all areas below baseline and above the curve are negative. Net incremental AUC = sum of these areas; this result was then divided by the study duration of the patients; negative value = improvement.	Baseline, Week 2, Week 4, Week 8, Week 12
Change From Baseline in the Chest Expansion Test at Weeks 2, 4, 8, 12	Measurement and remeasurement of standing maximal inspiration; chest circumference at nipple line or at 4th intercostal space in centimeters.	Week 2, Week 4, Week 8, Week 12
Change From Baseline in the Chest Expansion Test at Weeks 14, 18, 24	Measurement and remeasurement of standing maximal inspiration; chest circumference at nipple line or at 4th intercostal space in centimeters (cm).	Week 14, Week 18, Week 24
Change From Baseline in Level of Difficulty to Perform Physically Demanding Activities Due to Ankylosing Spondylitis at Weeks 2, 4, 8, 12	Subject evaluation of level of difficulty to perform daily physical activities and/or kinesitherapy for ankylosing spondylitis (AS) because of AS using a 100 millimeter Visual Analog Scale (VAS) ranging from 0=easy to 100=impossible. Subgroup of subjects who responded that they were able to perform daily physical activities and/or kinesitherapy for their ankylosing spondylitis at each visit.	Baseline, Week 2, Week 4, Week 8, Week 12
Change From Baseline in Self Assessment of Ability and or Easiness to Perform Physically Demanding Activities at Weeks 14, 18, 24	Subject evaluation of level of difficulty to perform daily physical activities and/or kinesitherapy for ankylosing spondylitis (AS) due to AS using a 100 millimeter Visual Analog Scale (VAS) ranging from 0=easy to 100=impossible. Subgroup of subjects who responded that they were able to perform daily physical activities and/or kinesitherapy for their ankylosing spondylitis at each visit.	Week 14, Week 18, Week 24
Normalized Net Incremental Area Under the Curve (AUC) for Erythtocyte Sedimentation Rate Between Baseline and Week 12	Normalized net incremental area under the curve (AUC) = area between baseline and the Erythrocyte Sedimentation Rate curve as a function of time (randomization to Week 12); computed using the linear trapezoidal method. All areas above baseline and under the curve are positive and all areas below baseline and above the curve are negative. Net incremental AUC = sum of these areas; this result was then divided by the study duration of the patients; negative value = improvement.	Baseline, Week 2, Week 4, Week 8, Week 12
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Weeks 2, 4, 8, 12	ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube. A higher rate is consistent with inflammation.	Week 2, Week 4, Week 8, Week 12
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Weeks 14, 18, 24	ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube. A higher rate is consistent with inflammation.	Week 14, Week 18, Week 24
Normalized Net Incremental Area Under the Curve (AUC) for C-reactive Protein Between Baseline and Week 12	Normalized net incremental area under the curve (AUC) = area between baseline and the C-reactive Protein curve as a function of time (randomization to Week 12); computed using the linear trapezoidal method. All areas above baseline and under the curve are positive and all areas below baseline and above the curve are negative. Net incremental AUC = sum of these areas; this result was then divided by the study duration of the patients; negative value = improvement.	Baseline, Week 2, Week 4, Week 8, Week 12
Change From Baseline in C-reactive Protein (CRP) at Weeks 2, 4, 8, 12	CRP is a marker of inflammation. A higher level is consistent with inflammation.	Baseline, Week 2, Week 4, Week 8, Week 12
Change From Baseline in C-reactive Protein (CRP) at Weeks 14, 18, 24	Change from baseline in C-reactive Protein (CRP).	Week 14, Week 18, Week 24
Percent of Subjects With Normal and Abnormal C-Reactive Protein at Weeks 14, 18, 24	Percent of participants with normal (<6 milligrams per liter) and abnormal (>= 6 milligrams per liter) C-Reactive Protein.	Week 14, Week 18, Week 24
Percent of Subjects With Patient Acceptable and Unacceptable Symptom State (PASS) at Weeks 2, 4, 8, 12	Percent of subjects reporting acceptable symptom state: acceptance to remain for the rest of their lives with the level of pain they had during the last 48 hours; and unacceptable symptom state: not able to remain for the rest of their lives with the level of pain they had during the last 48 hours. In the case of missing data, subjects who withdrew from the study because of inefficacy or toxicity were considered "unacceptable".	Week 2, Week 4, Week 8, Week 12
Percent of Subjects With Patient Acceptable and Unacceptable Symptom State (PASS) at Weeks 14, 18, 24	Percent of subjects reporting acceptable symptom state: acceptance to remain for the rest of their lives with the level of pain they had during the last 48 hours; and unacceptable symptom state: not able to remain for the rest of their lives with the level of pain they had during the last 48 hours. In the case of missing data, subjects who withdrew from the study because of inefficacy or toxicity were considered "unacceptable".	Week 14, Week 18, Week 24
Percent of Subjects With Minimum Clinically Important Improvement (MCII) in Pain Rating at Weeks 2, 4, 8, 12	Subjects were asked how their pain had been during the last 48 hours compared to baseline. Those subjects that reported improvement assessed how important this improvement was to them; range: very important, moderately important, slightly important, or not at all important. Binary response options: 1=improved very important, or improved moderately important; 2=slightly important, not at all important, no change, or worse-more pain.	Week 2, Week 4, Week 8, Week 12
Percent of Subjects With Minimum Clinially Important Improvement (MCII) at Weeks 14, 18, 24	Subjects were asked how their pain had been during the last 48 hours compared to baseline. Those subjects that reported improvement assessed how important this improvement was to them; range: very important, moderately important, slightly important, or not at all important. Binary response options: 1=improved very important, or improved moderately important; 2=slightly important, not at all important, no change, or worse-more pain.	Week 14, Week 18, Week 24

Collaborators and Investigators

• Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer
• Investigators: Principal Investigator: Trial Manager, For Hungary: WPBUMED@wyeth.com

Publications and helpful links

General Publications

• Dougados M, Braun J, Szanto S, Combe B, Geher P, Leblanc V, Logeart I. Continuous efficacy of etanercept in severe and advanced ankylosing spondylitis: results from a 12-week open-label extension of the SPINE study. Rheumatology (Oxford). 2012 Sep;51(9):1687-96. doi: 10.1093/rheumatology/kes125. Epub 2012 May 30.
• Dougados M, Braun J, Szanto S, Combe B, Geher P, Leblanc V, Logeart I. Nonsteroidal antiinflammatory drug intake according to the Assessment of SpondyloArthritis International Society Score in clinical trials evaluating tumor necrosis factor blockers: example of etanercept in advanced ankylosing spondylitis. Arthritis Care Res (Hoboken). 2012 Feb;64(2):290-4. doi: 10.1002/acr.20671.
• Dougados M, Braun J, Szanto S, Combe B, Elbaz M, Geher P, Thabut G, Leblanc V, Logeart I. Efficacy of etanercept on rheumatic signs and pulmonary function tests in advanced ankylosing spondylitis: results of a randomised double-blind placebo-controlled study (SPINE). Ann Rheum Dis. 2011 May;70(5):799-804. doi: 10.1136/ard.2010.139261. Epub 2011 Feb 13. Erratum In: Ann Rheum Dis. 2011 Jul;70(7):1349.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): February 1, 2009
• Study Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: January 8, 2007
• First Submitted That Met QC Criteria: January 8, 2007
• First Posted (Estimate): January 11, 2007

Study Record Updates

• Last Update Posted (Estimate): June 29, 2010
• Last Update Submitted That Met QC Criteria: June 24, 2010
• Last Verified: June 1, 2010

More Information

Terms related to this study

• Keywords: Adult; Axial Ankylosing Spondylitis
• Additional Relevant MeSH Terms: Infections; Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Spondylarthropathies; Bone Diseases, Infectious; Ankylosis; Spondylitis; Spondylarthritis; Spondylitis, Ankylosing; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Etanercept
• Other Study ID Numbers: 0881A3-403