Efficacy and Safety of Adalimumab in Patients With Active Rheumatoid Arthritis Treated Concomitantly With Methotrexate.

• ClinicalTrials.gov Identifier: NCT00195702
• Recruitment Status: Completed
• First Posted: September 20, 2005
• Results First Posted: March 1, 2010
• Last Update Posted: August 26, 2011
• Sponsor: Abbott
• Information provided by (Responsible Party): Abbott

Study Description

Brief Summary:

The purpose of the study was to assess the safety, immunogenicity, and clinical efficacy of adalimumab compared with placebo (during double-blind phase) and to to evaluate the long-term safety and maintenance of efficacy following repeated administration of adalimumab (during open-label extension phase) in patients with persistently active rheumatoid arthritis who were receiving concurrent methotrexate therapy.

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis	Biological: Adalimumab; Drug: Placebo	Phase 3

Detailed Description:

This was a 10-year study which had an initial 52-week, double-blind, placebo-controlled phase followed by an open-label extension phase up to 9 years in duration. Data were analyzed for the double-blind phase using all patients who were randomized and received at least one dose of study drug through Week 52 and for all patients who received at least one dose of adalimumab during the 10-year study (the Intent-to-Treat [ITT] population).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 619 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab in Rheumatoid Arthritis Patients Currently Receiving Treatment With Methotrexate
• Study Start Date: February 2000
• Actual Primary Completion Date: September 2002
• Actual Study Completion Date: August 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: DB adalimumab 20 mg ew; Subjects received 20 mg adalimumab subcutaneously (SC) once weekly (ew) and concomitant methotrexate (MTX) during the double-blind (DB) phase.	Biological: Adalimumab; Self-administered, subcutaneous injection of 20 mg adalimumab (1.6 mL/injection) once weekly (ew) for up to 52 weeks.; Other Names: ABT-D2E7; Humira
Experimental: DB adalimumab 40 mg eow; Subjects received 40 mg adalimumab subcutaneously (SC) every other week (eow) and concomitant methotrexate (MTX) during the double-blind (DB) phase. Subjects received placebo injections SC and concomitant MTX on the alternate weeks during the DB phase.	Biological: Adalimumab; Self-administered, subcutaneous injection of 40 mg adalimumab (1.6 mL/injection) every other week (eow) for up to 52 weeks.; Other Names: ABT-D2E7; Humira
Placebo Comparator: DB placebo ew; Subjects received placebo subcutaneously (SC) once weekly (ew) and concomitant methotrexate (MTX) during the double-blind (DB) phase.	Drug: Placebo; Self-administered, subcutaneous injection of placebo (1.6 mL/injection) once weekly (ew) for up to 52 weeks.
Experimental: DB adalimumab 20 mg ew/OL adalimumab 40 mg eow; Subjects received adalimumab 20 mg subcutaneously (SC) once weekly (ew) during the double-blind (DB) phase, then adalimumab 40 mg SC every other week (eow) during the open-label (OL) extension phase, along with concomitant methotrexate (MTX).	Biological: Adalimumab; Self-administration, subcutaneous (SC) injection of adalimumab 20 mg (1.6 mL/injection) once weekly (ew) for 52 weeks, followed by self-administration, SC injection of adalimumab 40 mg (0.8 mL/injection) every other week (eow) for up to Week 520.; Other Names: ABT-D2E7; Humira
Experimental: DB adalimumab 40 mg eow/OL adalimumab 40 mg eow; Subjects received adalimumab 40 mg subcutaneously (SC) every other week (eow) with placebo on alternate weeks during the double-blind (DB) phase, then adalimumab 40 mg SC eow during the open-label (OL) extension phase, along with concomitant methotrexate (MTX).	Biological: Adalimumab; Self-administration, subcutaneous (SC) injection of adalimumab 40 mg (1.6 mL/injection) every other week (eow) (with a placebo 1.6 mL/injection on alternate weeks) for 52 weeks, followed by self-administration, SC injection of adalimumab 40 mg (0.8 mL injection) eow for up to Week 520.; Other Names: ABT-D2E7; Humira
Experimental: DB placebo ew/OL adalimumab 40 mg eow; Subjects received placebo subcutaneously (SC) once weekly (ew) during the double-blind phase, then adalimumab 40 mg SC every other week (eow) during the open-label (OL) extension phase, along with concomitant methotrexate (MTX).	Biological: Adalimumab; Self-administration, subcutaneous (SC) injection of placebo solution (1.6 mL/injection) once weekly (ew) for 52 weeks, followed by self-administration, SC injection of adalimumab 40 mg (0.8 mL/injection) every other week (eow) for up to Week 520.; Other Names: ABT-D2E7; Humira

Outcome Measures

Primary Outcome Measures :

1. Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 24 [ Time Frame: Week 24 ]
   Patients were responders if they had: >= 20% improvement in tender joint count; >= 20% improvement in swollen joint count; and >= 20% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein. Patients withdrawing early or receiving additional disease-modifying anti-rheumatic drugs (DMARDs) after Week 16 were non-responders.
2. Change From Baseline in Modified Total Sharp X-ray Score at Week 52 [ Time Frame: Baseline and Week 52 ]
   Modified total Sharp x-ray score (mTSS) is a measure of change in joint health. Radiographs of hands/wrists and feet were obtained at screening and Week 52. Digitized images of these were scored in a blinded manner. Joints were scored for erosions from 0 (no damage) to 5 and for joint space narrowing from 0 (no damage) to 4; scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). Large positive change indicates disease progression; small positive/no change indicates slowing/halting of disease progression; and negative change may indicate improvement of disease.
3. Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 52 [ Time Frame: Baseline and Week 52 ]
   Subjects assessed their ability to perform the following tasks: 1) dress/groom; 2) arise; 3) eat; 4) walk; 5) reach; 6) grip; 7) maintain hygiene; and 8) maintain daily activity. Subjects assessed their ability to do these tasks over the past week by marking their response on a questionnaire. Possible responses/scores included the following: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Negative mean changes from baseline in the disability index of the HAQ indicated improvement.

Secondary Outcome Measures :

1. Number of Participants Meeting ACR20 Response Criteria at Week 52 [ Time Frame: Week 52 ]
   Patients were responders if they had: >= 20% improvement in tender joint count; >= 20% improvement in swollen joint count; and >= 20% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein. Patients withdrawing early or receiving additional disease-modifying anti-rheumatic drugs (DMARDs) after Week 16 were non-responders.
2. Change From Baseline in Modified Total Sharp X-ray Score at Week 24 [ Time Frame: Baseline and Week 24 ]
   Modified total Sharp x-ray score (mTSS) is a measure of change in joint health. Radiographs of hands/wrists and feet were obtained at screening and Week 24. Digitized images of these were scored in a blinded manner. Joints were scored for erosions from 0 (no damage) to 5 and for joint space narrowing from 0 (no damage) to 4; scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). Large positive change indicates disease progression; small positive/no change indicates slowing/halting of disease progression; and negative change may indicate improvement of disease.
3. Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 24 [ Time Frame: Baseline and Week 24 ]
   Subjects assessed their ability to perform the following tasks: 1) dress/groom; 2) arise; 3) eat; 4) walk; 5) reach; 6) grip; 7) maintain hygiene; and 8) maintain daily activity. Subjects assessed their ability to do these tasks over the past week by marking their response on a questionnaire. Possible responses/scores included the following: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Negative mean changes from baseline in the disability index of the HAQ indicated improvement.
4. Maintenance of the Disability Index of the HAQ at Week 52 for Participants Who Were Responders at Week 12 or Week 24 [ Time Frame: Week 52 ]
   Subjects assessed their ability to perform the following tasks: 1) dress/groom; 2) arise; 3) eat; 4) walk; 5) reach; 6) grip; 7) maintain hygiene; and 8) maintain daily activity. Subjects assessed their ability to do these tasks over the past week by marking their response on a questionnaire. Possible responses/scores included the following: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Responders had a >= 0.22-unit decrease (improvement) in HAQ scores from baseline to Week 12 or 24.
5. Maintenance of ACR20 Response at Week 52 for Participants Who Were ACR20 Responders at Week 24 [ Time Frame: Week 52 ]
   Patients were responders if they had: >= 20% improvement in tender joint count; >= 20% improvement in swollen joint count; and >= 20% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein. Patients withdrawing early or receiving additional disease-modifying anti-rheumatic drugs (DMARDs) after Week 16 were non-responders.
6. Number of Participants With a Continuous ACR70 Response for 6 Months During 52 Weeks of Treatment [ Time Frame: Baseline through Week 52 ]
   Patients were responders if they had: >= 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: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein. Patients withdrawing early or receiving additional disease-modifying anti-rheumatic drugs (DMARDs) after Week 16 were non-responders.
7. Time to First Response According to ACR20 Criteria - Number of Participants Meeting ACR20 Criteria for the First Time at Each Time Point [ Time Frame: Baseline through Week 52 ]
   Patients were responders if they had: >= 20% improvement in tender joint count; >= 20% improvement in swollen joint count; and >= 20% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein. Patients withdrawing early or receiving additional disease-modifying anti-rheumatic drugs (DMARDs) after Week 16 were non-responders.
8. Time to First Response According to ACR50 Criteria - Number of Participants Meeting ACR50 Criteria for the First Time at Each Time Point [ Time Frame: Baseline through Week 52 ]
   Patients were responders if they had: >= 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: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein. Patients withdrawing early or receiving additional disease-modifying anti-rheumatic drugs (DMARDs) after Week 16 were non-responders.
9. Time to First Response According to ACR70 Criteria - Number of Participants Meeting ACR70 Criteria for the First Time at Each Time Point [ Time Frame: Baseline through Week 52 ]
   Patients were responders if they had: >= 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: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein. Patients withdrawing early or receiving additional disease-modifying anti-rheumatic drugs (DMARDs) after Week 16 were non-responders.
10. Estimated Yearly Progression of Rheumatoid Arthritis [ Time Frame: Baseline and Week 52 ]
    Estimated yearly progression was defined as modified total Sharp x-ray score at baseline divided by duration of rheumatoid arthritis disease at baseline. Actual progression during the study was defined as modified total Sharp x-ray score at Week 52 minus modified total Sharp x-ray score at baseline divided by the duration of the study. The range of scores for the modified total Sharp x-ray score was 0 (normal) to 398 (maximal disease).

Other Outcome Measures:

1. Baseline Measure: Gender - Female/Male - for the Any Adalimumab Through Year 10 Group (Intent-to-Treat) [ Time Frame: Baseline for Intent-to-Treat (Any Adalimumab Through Year 10) Group ]
   Gender (female/male) recorded at Baseline for the Intent-to-Treat population (the Any Adalimumab Through Year 10 group) of the study. This measure was not included in the Baseline Characteristics section due to the difficulty of maintaining correct subject numbers and totals in that section.
2. Baseline Measure: Age Categories for the Any Adalimumab Through Year 10 Group (Intent-to-Treat) [ Time Frame: Baseline for Intent-to-Treat (Any Adalimumab Through Year 10) Group ]
   Age recorded at Baseline, reported by category, for the Intent-to-Treat population (the Any Adalimumab Through Year 10 group) of the study. This measure was not included in the Baseline Characteristics section due to the difficulty of maintaining correct subject numbers and totals in that section.
3. Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 260 [ Time Frame: Week 260 ]
   Patients were responders if they had: >= 20% improvement in tender joint count; >= 20% improvement in swollen joint count; and >= 20% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein.
4. Number of Participants Meeting the American College of Rheumatology 20% (ACR20) Response Criteria at Week 520 [ Time Frame: Week 520 ]
   Patients were responders if they had: >= 20% improvement in tender joint count; >= 20% improvement in swollen joint count; and >= 20% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein.
5. Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 260 [ Time Frame: Week 260 ]
   Patients were responders if they had: >= 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: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein.
6. Number of Participants Meeting the American College of Rheumatology 50% (ACR50) Response Criteria at Week 520 [ Time Frame: Week 520 ]
   Patients were responders if they had: >= 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: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein.
7. Number of Participants Meeting the American College of Rheumatology 70% (ACR70) Response Criteria at Week 260 [ Time Frame: Week 260 ]
   Patients were responders if they had: >= 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: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein.
8. Number of Participants Meeting the American College of Rheumatology 70% (ACR70) Response Criteria at Week 520 [ Time Frame: Week 520 ]
   Patients were responders if they had: >= 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: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein.
9. Number of Participants With a Continuous American College of Rheumatology 70% (ACR70) Response for at Least 6 Months Through Year 10 [ Time Frame: Baseline through Week 520 ]
   Patients were responders if they had: >=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: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein.
10. Number of Participants With at Least a 0.22 Reduction From Baseline in the Health Assessment Questionnaire (HAQ) Disability Index at Week 260 [ Time Frame: Week 260 ]
    The Health Assessment Questionnaire (HAQ) Disability Index is a self-reported measure of disability, which assesses the patient's ability to perform the following tasks: dress and groom; arise; eat; walk; reach; grip; maintain hygiene; and maintain daily activity. Possible responses/scores are 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do). Negative mean changes from Baseline indicate improvement. An improvement of 0.22 in score (a -0.22 or greater reduction from Baseline score) is a minimally clinically significant change.
11. Number of Participants With at Least a 0.22 Reduction From Baseline in the Health Assessment Questionnaire (HAQ) Disability Index at Week 520 [ Time Frame: Week 520 ]
    The Health Assessment Questionnaire (HAQ) Disability Index is a self-reported measure of disability, which assesses the patient's ability to perform the following tasks: dress and groom; arise; eat; walk; reach; grip; maintain hygiene; and maintain daily activity. Possible responses/scores are 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do). Negative mean changes from Baseline indicate improvement. An improvement of 0.22 in score (a -0.22 or greater reduction from Baseline score) is a minimally clinically significant change.
12. Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 260 [ Time Frame: Baseline and Week 260 ]
    Subjects assessed their ability to perform the following tasks: 1) dress/groom; 2) arise; 3)eat; 4) walk; 5) reach; 6) grip; 7) maintain hygiene; and 8) maintain daily activity. Subjects assessed their ability to do these tasks over the past week by marking their response on a questionnaire. Possible responses/scores were: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Negative mean changes from Baseline in the disability index of the HAQ indicated improvement.
13. Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 520 [ Time Frame: Baseline and Week 520 ]
    Subjects assessed their ability to perform the following tasks: 1) dress/groom; 2) arise; 3)eat; 4) walk; 5) reach; 6) grip; 7) maintain hygiene; and 8) maintain daily activity. Subjects assessed their ability to do these tasks over the past week by marking their response on a questionnaire. Possible responses/scores were: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Negative mean changes from Baseline in the disability index of the HAQ indicated improvement.
14. Change From Baseline in Modified Total Sharp X-ray Score at Week 416 [ Time Frame: Baseline and Week 416 ]
    Modified total Sharp x-ray score (mTSS) is a measure of change in joint health. Radiographs of hands/wrists and feet were obtained at screening and Week 416. Digitized images of these were scored in a blinded manner. Joints were scored for erosions from 0 (no damage) to 5 and for joint space narrowing from 0 (no damage) to 4; scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). Large positive change indicates disease progression; small positive/no change indicates slowing/halting of disease progression; and negative change may indicate improvement of disease.
15. Change From Baseline in Modified Total Sharp X-ray Score at Week 520 [ Time Frame: Baseline and Week 520 ]
    Modified total Sharp x-ray score (mTSS) is a measure of change in joint health. Radiographs of hands/wrists and feet were obtained at screening and Week 520. Digitized images of these were scored in a blinded manner. Joints were scored for erosions from 0 (no damage) to 5 and for joint space narrowing from 0 (no damage) to 4; scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). Large positive change indicates disease progression; small positive/no change indicates slowing/halting of disease progression; and negative change may indicate improvement of disease.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age 18 or older and in good health (Investigator discretion) with a recent stable medical history
• Met American College of Rheumatology (ACR) criteria for diagnosis of active rheumatoid arthritis (RA) and had at both screening and baseline visits >=6 swollen joints and >=9 tender joints, despite a minimum of 3-months treatment with methotrexate (MTX). (Distal interphalangeal joints [DIPs] were not to be included in joint count for inclusion. The screening and baseline visits could be 3 to 28 days apart for patients not previously receiving disease-modifying anti-rheumatic drugs [DMARDs] other than MTX or 4 to 6 weeks for patients requiring a DMARD washout period.)
• Insufficient efficacy with MTX 12.5 to 25 mg per week (10 mg per week if MTX intolerant).
• If patient on a second-line treatment (DMARD) other than MTX, he/she had to discontinue it for at least 28 days before the baseline visit (the washout period).
• Treatment with oral folic acid 1-3 mg/day or, if appropriate, up to 10 mg leucovorin per week.
• Both rheumatoid factor positivity and a C-reactive protein value >=1 mg/dL, or at least one joint erosion on X-ray.

Exclusion Criteria:

• Subject considered by the investigator, for any reason, to be an unsuitable candidate for the study.
• Female subject who was pregnant or breast-feeding or considering becoming pregnant.
• Preceding treatment with any tumor necrosis factor (TNF) antagonist, including adalimumab.
• Prior exposure to alkylating agents, such as chlorambucil or cyclophosphamide.
• Intra-articular, intramuscular, or intravenous administration of corticosteroids within 4 weeks prior to the screening visit.
• Subject was wheelchair bound or bedridden.

Contacts and Locations

Locations

United States, Alabama

Site Ref # / Investigator 424

Huntsville, Alabama, United States, 35801

Site Ref # / Investigator 2510

Mobile, Alabama, United States, 36608

United States, Arizona

Site Ref # / Investigator 60729

Phoenix, Arizona, United States, 85012

Site Ref # / Investigator 725

Scottsdale, Arizona, United States, 85260

United States, California

Site Ref # / Investigator 60736

Anaheim, California, United States, 92801

Site Ref # / Investigator 360

Escondido, California, United States, 92025

Site Ref # / Investigator 714

La Jolla, California, United States, 92037-0943

Site Ref # / Investigator 469

La Jolla, California, United States, 92037

Site Ref # / Investigator 419

Palm Desert, California, United States, 92260

Site Ref # / Investigator 492

San Jose, California, United States, 95126

Site Ref # / Investigator 60734

San Louis Obispo, California, United States, 93405

Site Ref # / Investigator 60739

Van Nuys, California, United States, 91405

United States, Connecticut

Site Ref # / Investigator 712

Danbury, Connecticut, United States, 06810

United States, Florida

Site Ref # / Investigator 710

Aventura, Florida, United States, 33180

Site Ref # / Investigator 498

Dunedin, Florida, United States, 34698

Site Ref # / Investigator 499

Orlando, Florida, United States, 32806

Site Ref # / Investigator 729

Tampa, Florida, United States, 33614

Site Ref # / Investigator 463

Zephyrhills, Florida, United States, 33542

United States, Idaho

Site Ref # / Investigator 2436

Boise, Idaho, United States, 83704

Site Ref # / Investigator 485

Idaho Falls, Idaho, United States, 83404

United States, Illinois

Site Ref # / Investigator 60732

Chicago, Illinois, United States, 60611

Site Ref # / Investigator 726

Springfield, Illinois, United States, 62704

United States, Indiana

Site Ref # / Investigator 2506

Indianapolis, Indiana, United States, 46260

Site Ref # / Investigator 732

South Bend, Indiana, United States, 46601

United States, Kansas

Site Ref # / Investigator 60730

Shawnee Mission, Kansas, United States, 66216

Site Ref # / Investigator 467

Wichita, Kansas, United States, 67203

Site Ref # / Investigator 494

Wichita, Kansas, United States, 67208

United States, Kentucky

Site Ref # / Investigator 491

Lexington, Kentucky, United States, 40509

United States, Maine

Site Ref # / Investigator 2508

Portland, Maine, United States, 04102

United States, Maryland

Site Ref # / Investigator 392

Baltimore, Maryland, United States, 21239

Site Ref # / Investigator 354

Cumberland, Maryland, United States, 21502

Site Ref # / Investigator 730

Wheaton, Maryland, United States, 20902

United States, Massachusetts

Site Ref # / Investigator 465

Burlington, Massachusetts, United States, 01805

Site Ref # / Investigator 2512

Worcester, Massachusetts, United States, 01610

United States, Michigan

Site Ref # / Investigator 471

Grand Rapids, Michigan, United States, 49506

Site Ref # / Investigator 473

Kalamazoo, Michigan, United States, 49009

United States, Missouri

Site Ref # / Investigator 731

Kansas City, Missouri, United States, 64114

Site Ref # / Investigator 502

St. Louis, Missouri, United States, 63110

Site Ref # / Investigator 482

St. Louis, Missouri, United States, 63128

Site Ref # / Investigator 371

St. Louis, Missouri, United States, 63141

United States, Nebraska

Site Ref # / Investigator 487

Omaha, Nebraska, United States, 68114

United States, New Hampshire

Site Ref # / Investigator 353

Concord, New Hampshire, United States, 03301

Site Ref # / Investigator 364

Dover, New Hampshire, United States, 03820

United States, New Jersey

Site Ref # / Investigator 60726

Mercerville, New Jersey, United States, 08619

Site Ref # / Investigator 358

Voorhees, New Jersey, United States, 08043

United States, New York

Site Ref # / Investigator 483

Rochester, New York, United States, 14609

United States, North Carolina

Site Ref # / Investigator 512

Durham, North Carolina, United States, 27704

Site Ref # / Investigator 340

Greensboro, North Carolina, United States, 27408

Site Ref # / Investigator 461

Raleigh, North Carolina, United States, 27609

Site Ref # / Investigator 500

Raleigh, North Carolina, United States, 27609

Site Ref # / Investigator 60731

Raleigh, North Carolina, United States, 27612

Site Ref # / Investigator 60737

Salisbury, North Carolina, United States, 28144

United States, Ohio

Site Ref # / Investigator 456

Mayfield Village, Ohio, United States, 44143

United States, Oklahoma

Site Ref # / Investigator 470

Oklahoma City, Oklahoma, United States, 73112

Site Ref # / Investigator 60723

Oklahoma, Oklahoma, United States, 73112

United States, Oregon

Site Ref # / Investigator 422

Eugene, Oregon, United States, 97401

United States, Pennsylvania

Site Ref # / Investigator 60735

Colmar, Pennsylvania, United States, 18915-9671

Site Ref # / Investigator 2507

Duncansville, Pennsylvania, United States, 16635

Site Ref # / Investigator 717

East Norriton, Pennsylvania, United States, 19401

Site Ref # / Investigator 352

Mechanicsburg, Pennsylvania, United States, 17055

Site Ref # / Investigator 480

Wexford, Pennsylvania, United States, 15090

Site Ref # / Investigator 2511

Wyomissing, Pennsylvania, United States, 19610

Site Ref # / Investigator 60724

Wyomissing, Pennsylvania, United States, 19610

United States, South Carolina

Site Ref # / Investigator 718

Charleston, South Carolina, United States, 29406

United States, Tennessee

Site Ref # / Investigator 460

Memphis, Tennessee, United States, 38119

Site Ref # / Investigator 462

Nashville, Tennessee, United States, 37205

United States, Texas

Site Ref # / Investigator 716

Austin, Texas, United States, 78705

Site Ref # / Investigator 60728

Galveston, Texas, United States, 77555-0759

Site Ref # / Investigator 2509

Houston, Texas, United States, 77074

Site Ref # / Investigator 510

Houston, Texas, United States, 77074

United States, Virginia

Site Ref # / Investigator 60725

Falls Church, Virginia, United States, 22044

Site Ref # / Investigator 711

Richmond, Virginia, United States, 23219

United States, Washington

Site Ref # / Investigator 509

Seattle, Washington, United States, 98166-2967

Site Ref # / Investigator 356

Spokane, Washington, United States, 99204

Site Ref # / Investigator 464

Tacoma, Washington, United States, 98405

United States, Wisconsin

Site Ref # / Investigator 60738

Kenosha, Wisconsin, United States, 53142

Canada, Alberta

Site Ref # / Investigator 475

Calgary, Alberta, Canada, T2N 4N1

Canada, British Columbia

Site Ref # / Investigator 495

Penticton, British Columbia, Canada, V2A 3G8

Site Ref # / Investigator 2496

Richmond, British Columbia, Canada, V7C 5L9

Canada, Manitoba

Site Ref # / Investigator 2495

Winnipeg, Manitoba, Canada, R3N OK6

Canada, Nova Scotia

Site Ref # / Investigator 496

Halifax, Nova Scotia, Canada, B3H 4K4

Canada, Ontario

Site Ref # / Investigator 444

Newmarket, Ontario, Canada, L3Y 3R7

Site Ref # / Investigator 2497

Toronto, Ontario, Canada, M4N 3M5

Site Ref # / Investigator 478

Toronto, Ontario, Canada, M5L 3L9

Site Ref # / Investigator 421

Toronto, Ontario, Canada, M5T 2S8

Canada, Quebec

Site Ref # / Investigator 363

Montreal, Quebec, Canada, H3Z 2Z3

Canada, Saskatchewan

Site Ref # / Investigator 60702

Saskatoon, Saskatchewan, Canada, S7N 0W8

Sponsors and Collaborators

Abbott

Investigators

• Study Director: Laura Redden, MD, PhD; Abbott

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Smolen J, Fleischmann R, Aletaha D, Li Y, Zhou Y, Sainsbury I, Galindo IL. Disease activity improvements with optimal discriminatory ability between treatment arms: applicability in early and established rheumatoid arthritis clinical trials. Arthritis Res Ther. 2019 Nov 10;21(1):231. doi: 10.1186/s13075-019-2005-9.

Keystone EC, Breedveld FC, van der Heijde D, van Vollenhoven RF, Emery P, Smolen JS, Sainsbury I, Florentinus S, Kupper H, Chen K, Kavanaugh A. Achieving comprehensive disease control in patients with early and established rheumatoid arthritis treated with adalimumab plus methotrexate versus methotrexate alone. RMD Open. 2017 Sep 26;3(2):e000445. doi: 10.1136/rmdopen-2017-000445. eCollection 2017.

Burmester GR, Landewe R, Genovese MC, Friedman AW, Pfeifer ND, Varothai NA, Lacerda AP. Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis. Ann Rheum Dis. 2017 Feb;76(2):414-417. doi: 10.1136/annrheumdis-2016-209322. Epub 2016 Jun 23.

Emery P, Kavanaugh A, Bao Y, Ganguli A, Mulani P. Comprehensive disease control (CDC): what does achieving CDC mean for patients with rheumatoid arthritis? Ann Rheum Dis. 2015 Dec;74(12):2165-74. doi: 10.1136/annrheumdis-2014-205302. Epub 2014 Aug 19.

Landewe R, Ostergaard M, Keystone EC, Florentinus S, Liu S, van der Heijde D. Analysis of integrated radiographic data from two long-term, open-label extension studies of adalimumab for the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2015 Feb;67(2):180-6. doi: 10.1002/acr.22426.

Keystone EC, van der Heijde D, Kavanaugh A, Kupper H, Liu S, Guerette B, Mozaffarian N. Clinical, functional, and radiographic benefits of longterm adalimumab plus methotrexate: final 10-year data in longstanding rheumatoid arthritis. J Rheumatol. 2013 Sep;40(9):1487-97. doi: 10.3899/jrheum.120964. Epub 2013 Jul 1.

Keystone EC, Kavanaugh A, Weinblatt ME, Patra K, Pangan AL. Clinical consequences of delayed addition of adalimumab to methotrexate therapy over 5 years in patients with rheumatoid arthritis. J Rheumatol. 2011 May;38(5):855-62. doi: 10.3899/jrheum.100752. Epub 2011 Feb 1.

• Responsible Party: Abbott
• ClinicalTrials.gov Identifier: NCT00195702
• Other Study ID Numbers: DE019
• First Posted: September 20, 2005
• Results First Posted: March 1, 2010
• Last Update Posted: August 26, 2011
• Last Verified: August 2011

Keywords provided by Abbott:

Rheumatoid Arthritis

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Adalimumab; Tumor Necrosis Factor Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents