To evaluate the potential of adalimumab to inhibit radiographic progression in joint destruction compared with placebo in adult Japanese subjects with recent onset of rheumatoid arthritis.
This was a Phase 3 multicenter, randomized, double-blind, parallel group, placebo-controlled study designed to evaluate the inhibition of radiographic progression by adalimumab compared with placebo in adult Japanese patients with early rheumatoid arthritis (RA) who had not been previously treated with methotrexate (MTX). Eligible participants were randomized 1:1 to receive either a subcutaneous injection of adalimumab 40 mg or matching placebo every other week (eow) during the 26-week double-blind phase. All participants also received 6 mg to 8 mg MTX weekly as basal treatment for their disease. Participants who experienced an increase in disease activity (more than 20% increase in tender joint count and swollen joint count) at Week 12, 16, or 20 compared with Baseline after having increased MTX dose to 8 mg per week for at least 4 weeks were discontinued from the double-blind phase and were eligible to receive open-label adalimumab 40 mg eow as rescue treatment. Participants who completed the 26 weeks of treatment (either double-blind study drug \[adalimumab or placebo\] treatment or open-label adalimumab treatment) were eligible to enter the 26-week open-label phase in which they received adalimumab 40 mg eow. Efficacy and safety assessments were performed at Baseline and at designated study visits.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
334
Double-blind adalimumab 40 mg administered subcutaneously (SC) every other week (eow)
Double-blind adalimumab-matching placebo administered subcutaneously (SC)every other week (eow)
Open-label adalimumab 40 mg administered subcutaneously (SC) every other week (eow) after completion of the first 26 weeks in the study
Change From Baseline in Modified Total Sharp X-Ray Score at Week 26
Modified Total Sharp Score (mTSS) is a measure of joint health, used in evaluation of inhibition of radiographic progression of disease. Digitized X-rays of hands and feet were obtained then scored in a blinded manner: for erosions (0 \[no damage\] to 5 \[complete collapse or total destruction of joint\]) and for joint space narrowing (0 \[no damage\] to 4 \[complete luxation of joint\]). Scores were added, giving total mTSS (0 \[normal\] to 380 \[maximal disease\]). Large positive change in mTSS indicates disease progression; small positive/no change indicates slowing/halting of disease progression.
Time frame: Baseline, Week 26
Number of Participants Meeting ACR20 Response Criteria at Week 26 (ACR: American College of Rheumatology)
Patients were ACR20 responders if they had: \>= 20% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus \>=20% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and acute phase reactant C-reactive protein. Patients who discontinued or switched to open-label adalimumab prior to Week 26 were considered non-responders.
Time frame: Week 26
Number of Participants Meeting ACR50 Response Criteria at Week 26 (ACR: American College of Rheumatology)
Patients were ACR50 responders if they had: \>= 50% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus \>=50% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and acute phase reactant C-reactive protein. Patients who discontinued or switched to open-label adalimumab prior to Week 26 were considered non-responders.
Time frame: Week 26
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Open-label adalimumab 40 mg administered subcutaneously (SC) every other week (eow) as rescue treatment to complete the first 26 weeks in the study- dependent on participant eligibility (increase in disease activity), applies to Weeks 12 to 26
Site Reference ID/Investigator# 46861
Anjo, Japan
Site Reference ID/Investigator# 46919
Aomori, Japan
Site Reference ID/Investigator# 46805
Chiba, Japan
Site Reference ID/Investigator# 46806
Chiba, Japan
Site Reference ID/Investigator# 46880
Chiba, Japan
Site Reference ID/Investigator# 46881
Chiba, Japan
Site Reference ID/Investigator# 46890
Fuchū, Japan
Site Reference ID/Investigator# 46902
Fukuoka, Japan
Site Reference ID/Investigator# 46903
Fukuoka, Japan
Site Reference ID/Investigator# 46904
Fukuoka, Japan
...and 78 more locations
Number of Participants Meeting ACR70 Response Criteria at Week 26 (ACR: American College of Rheumatology)
Patients were ACR70 responders if they had: \>= 70% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus \>=70% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and acute phase reactant C-reactive protein. Patients who discontinued or switched to open-label adalimumab prior to Week 26 were considered non-responders.
Time frame: Week 26
Change From Baseline in Disease Activity Score (DAS28[ESR]) at Week 26
Disease Activity Score (DAS28) is a combined index used to measure disease activity in patients with rheumatoid arthritis. Calculation of the DAS28 score used the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity, and the erythrocyte sedimentation rate. DAS28(ESR) scores range from 0 (no disease activity) to 9 (maximal disease activity); decrease is indicative of improvement in disease activity.
Time frame: Baseline, Week 26
Number of Participants Achieving Clinical Remission, Defined by Disease Activity Score (DAS28[ESR]) <2.6, at Week 26
Disease Activity Score (DAS28) is a combined index used to measure disease activity in patients with rheumatoid arthritis. Calculation of the DAS28 score used the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity, and the erythrocyte sedimentation rate. DAS28(ESR) scores range from 0 (no disease activity) to 9 (maximal disease activity); decrease is indicative of improvement in disease activity. DAS28(ESR) score \<2.6 was defined as clinical remission of disease.
Time frame: Week 26
Number of Participants Who Reported Any Adverse Event (Serious or Non-serious) on Double-blind Study Drug Through Week 26
Adverse events were collected at designated study visits for all participants who were randomized and received at least 1 dose of study drug. The number of participants who experienced any adverse event (serious or non-serious) while receiving double-blind study drug is summarized. See the Reported Adverse Event section for details.
Time frame: Through Week 26
Change From Baseline in Modified Total Sharp X-Ray Score at Week 52
Modified Total Sharp Score (mTSS) is a measure of joint health, used in evaluation of inhibition of radiographic progression of disease. Digitized X-rays of hands and feet were obtained then scored in a blinded manner: for erosions (0 \[no damage\] to 5 \[complete collapse or total destruction of joint\]) and for joint space narrowing (0 \[no damage\] to 4 \[complete luxation of joint\]). Scores were added, giving total mTSS score (0 \[normal\] to 380 \[maximal disease\]). Large positive change in mTSS indicates diseae progression; small positive/no change indicates slowing/halting of disease progression.
Time frame: Baseline, Week 52
Number of Participants Meeting ACR20 Response Criteria at Week 52 (ACR: American College of Rheumatology)
Patients were ACR20 responders if they had: \>=20% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus \>=20% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire (HAQ); and acute phase reactant C-reactive protein.
Time frame: Week 52
Number of Participants Meeting ACR50 Response Criteria at Week 52 (ACR: American College of Rheumatology)
Patients were ACR50 responders if they had: \>=50% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus \>=50% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire (HAQ); and acute phase reactant C-reactive protein.
Time frame: Week 52
Number of Participants Meeting ACR70 Response Criteria at Week 52 (ACR: American College of Rheumatology)
Patients were ACR70 responders if they had: \>=70% improvement in both tender joint count (68 joints) and in swollen joint count (66 joints) plus \>=70% improvement in at least 3 of the 5 remaining ACR core measures: patient's assessment of pain; patient's global assessment of disease activity; physician's global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire (HAQ); and acute phase reactant C-reactive protein.
Time frame: Week 52
Change From Baseline in Disease Activity Score (DAS28[ESR]) at Week 52
Disease Activity Score (DAS28) is a combined index used to measure disease activity in patients with rheumatoid arthritis. Calculation of the DAS28 score used the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity, and the erythrocyte sedimentation rate. DAS28(ESR) scores range from 0 (no disease activity) to 9 (maximal disease activity); decrease is indicative of improvement in disease activity.
Time frame: Baseline, Week 52
Number of Participants Achieving Clinical Remission, Defined by Disease Activity Score (DAS28[ESR]) <2.6, at Week 52
Disease Activity Score (DAS28) is a combined index used to measure disease activity in patients with rheumatoid arthritis. Calculation of the DAS28 score used the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity, and the erythrocyte sedimentation rate. DAS28(ESR) scores range from 0 (no disease activity) to 9 (maximal disease activity); decrease is indicative of improvement in disease activity. DAS28(ESR) score \<2.6 was defined as clinical remission of disease.
Time frame: Week 52
Number of Participants Who Reported Any Adverse Event (Serious or Non-serious) While Receiving Adalimumab Through Week 52
Adverse events were collected at designated study visits for all participants who were randomized and received at least 1 dose of adalimumab. The number of participants who experienced any adverse event (serious or non-serious) while receiving any adalimumab during the study (double-blind adalimumab and/or open-label) is summarized. See the Reported Adverse Event section for details.
Time frame: Through Week 52