The purpose of this study is to examine the effects of etanercept (10 mg and 25 mg) compared with methotrexate (up to 8 mg per week) on the slowing of joint destruction.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
550
10 mg twice weekly, subcutaneous injection for 52 weeks
25 mg, twice weekly, subcutaneous injection for 52 weeks
up to 8 mg per week, oral dosing for 52 weeks
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 52
mTSS = sum of erosion and JSN scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Change = scores at observation minus score at Baseline. An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represents improvement.
Time frame: Week 52
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 24
mTSS = sum of erosion and JSN scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Change = scores at observation minus score at Baseline. An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represents improvement.
Time frame: Week 24
Change From Baseline in Erosion Score at Weeks 24 and 52
Joint erosion score: erosion severity in 44 joints (16 per hand, 6 per foot). Each joint scored according to surface area involved, from 0 (no erosion) to 5 (extensive bone loss from more than one half of articulating bone). Because each side of foot joint was graded, maximum erosion score for foot joint was 10. Thus, maximum erosion score was 280. Change = score at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time frame: Baseline, Week 24, and Week 52
Change From Baseline in Joint Space Narrowing (JSN) Score at Weeks 24 and 52
JSN score: severity of JSN in 42 joints (15 per hand and 6 per foot), including subluxation, scored from 0 (no/normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation). Maximum JSN score was 168. Change = scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
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Pfizer Investigational Site
Nagoya, Aichi-ken, Japan
Pfizer Investigational Site
Nagoya, Aichi-ken, Japan
Pfizer Investigational Site
Goshogawara, Aomori, Japan
Pfizer Investigational Site
Asahi, Chiba, Japan
Pfizer Investigational Site
Matsuyama, Ehime, Japan
Pfizer Investigational Site
Fukui-shi, Fukui, Japan
Pfizer Investigational Site
Fukuoka, Fukuoka, Japan
Pfizer Investigational Site
Fukuoka, Fukuoka, Japan
Pfizer Investigational Site
Fukuoka, Fukuoka, Japan
Pfizer Investigational Site
Iizuka, Fukuoka, Japan
...and 31 more locations
Time frame: Baseline, Week 24, and Week 52
Percentage of Participants With no Progression of Joint Destruction at Week 52
Absence of joint destruction defined by 3 categories (mTSS change \<=0.5, \<=3.0, and \<smallest detectable difference \[SDD\] where SDDs were scores \>3.0). mTSS = sum of erosion and JSN scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score).
Time frame: Baseline and Week 52
Change From Baseline in Swollen Joint Count at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
American College of Rheumatology (ACR) swollen joint count was an assessment of 68 joints. Joints classified as either swollen or not swollen. Change = scores at observation minus score at Baseline, and total possible scores ranged from -68 to 68. An increase in swollen joints from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Change From Baseline in Number of Painful Joints on Pressure or on Motion at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
71 joints assessed by the investigator using criteria based on pressure and joint manipulation. Change = scores at observation minus score at Baseline, and total possible scores ranged from -71 to 71. An increase in tender joint count from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Change From Baseline in Physician's Global Assessment of Symptoms at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Physician Global Assessment of symptoms, assessed using a 11-point rating scale, where 0=asymptomatic and 10=severe symptoms. Change = scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Change From Baseline in Patient's Global Assessment at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Patient's Global Assessment of symptoms, assessed using a 11-point rating scale, where 0=asymptomatic and 10=severe symptoms. Change = scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Change From Baseline in Mean Duration of Morning Stiffness at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Morning stiffness in and around the joints lasting at least 1 hour before maximal improvement. Change = scores at observation minus score at Baseline. An increase in stiffness duration from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Change From Baseline in Visual Analogue Scale for Pain (VAS-pain) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
100 millimeter (mm) line (VAS) marked by participant. Intensity of pain range (over past week): 0mm = no pain to 100mm = worst possible pain. Change = scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Change From Baseline in VAS for Participant General Health at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
100mm line (VAS) marked by participant. Participants asked, "In general how would you rate your health over the last 2-3 weeks?" 0mm=very well to 100mm=extremely bad. Change = scores at observation minus score at Baseline. An increase in score from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
HAQ-DI: participant-reported assessment of ability to perform tasks: 1) dress/groom; 2) arise; 3) eat; 4) walk; 5) reach; 6) grip; 7) hygiene; and 8) common activities over past week. Each item scored on 4-point Likert scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Change = scores at observation minus score at Baseline and total possible scores ranged from -3 to 3. An increase in score from baseline represented disease progression and/or joint worsening and a decrease represented improvement.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response
ACR20 response: greater than or equal to (≥) 20 percent (%) improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP).
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Percentage of Participants With an ACR50 Response
ACR50 response: ≥ 50% improvement in tender joint count; ≥ 50% improvement in swollen joint count; and ≥ 50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Percentage of Participants With an ACR70 Response
ACR70 response: ≥ 70% improvement in tender joint count; ≥ 70% improvement in swollen joint count; and ≥ 70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Change From Baseline in Disease Activity Score (DAS) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
DAS: weighted calculation of joint tenderness score (Ritchie Articular Index\[RAI\]), swollen joint count of 44 joints, natural logarithm (ln) of erythrocyte sedimentation rate (ESR) in millimeters per hour (mm/hr), and general health (GH) using VAS. RAI defined as sum of 26 possible 0 to 3 tender scores. DAS = 0.53938 square root (√) (RAI) + 0.06465 (swollen joint count) + 0.330 (ln ESR) + 0.00722 (GH). Change from baseline = DAS at Week x minus Baseline DAS. Total DAS scores could range from 10 (worse outcome) to 0 (better outcome).
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Change From Baseline in Disease Activity Score in 28 Joints (DAS28) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
DAS based on 28 painful joint counts, 28 swollen joint counts, ESR, and GH. DAS28 score calculated as 0.56 √ (28 painful joint count) + 0.28 √ (28 swollen joint count) + 0.70 (ln ESR mm/hr) + 0.014 GH. Change from baseline = DAS at Week x minus Baseline DAS. Total DAS scores could range from 10 (worse outcome) to 0 (better outcome).
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Change From Baseline in C-reactive Protein (CRP) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
CRP: marker of inflammation. Higher level consistent with inflammation. Normal CRP range: 0 to 1.0 milligrams per deciliter (mg/dL).
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
ESR: laboratory test that provided a non-specific measure of inflammation. The test assessed the rate at which red blood cells fell in a test tube and was measured in mm/hour. Normal range: 0-30mm/h. Higher rate consistent with inflammation.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52