Study of the Optimal Protocol for Methotrexate and Adalimumab Combination Therapy in Early Rheumatoid Arthritis (OPTIMA)

• ClinicalTrials.gov Identifier: NCT00420927
• Recruitment Status: Completed
• First Posted: January 11, 2007
• Results First Posted: September 29, 2011
• Last Update Posted: April 18, 2012
• Sponsor: Abbott
• Information provided by (Responsible Party): Abbott

Study Description

Brief Summary:

This study compared the safety and efficacy of combination therapy with adalimumab plus methotrexate (MTX) to that of MTX monotherapy (i.e., placebo plus MTX) in subjects with early rheumatoid arthritis (RA).

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis	Biological: adalimumab; Drug: methotrexate; Biological: placebo	Phase 4

Detailed Description:

This was a 78-week, multicenter, randomized, double-blind, double-treatment period study designed to compare the safety and efficacy of adalimumab and MTX with placebo and MTX in subjects with early RA. Subjects were randomized to receive adalimumab 40 mg every other week (eow) or placebo subcutaneous injections in combination with orally administered MTX for 26 weeks (Period 1). All subjects in all arms received open-label MTX weekly throughout the study (both Period 1 and Period 2).

At Weeks 22 and 26, subjects were assessed for achievement of low disease activity, defined as a DAS28 score below 3.2. DAS28 is a measure of RA disease activity calculated using the number of tender and swollen joints (out of a total of 28), C-reactive protein level (CRP, a blood marker of inflammation), and the patient's global assessment of disease activity (indicated by marking a 10 cm line between very good and very bad). Subjects who achieved low disease activity at Week 22 and 26 in the adalimumab arm at the end of Period 1 were randomized to receive MTX monotherapy (placebo and MTX) or combination therapy (adalimumab and MTX) in a 1:1 ratio for the duration of Period 2 (52 weeks, i.e., to Week 78 of the study). Subjects achieving low disease activity at Week 22 and 26 in the placebo arm (MTX monotherapy) at the end of Period 1 continued to receive MTX monotherapy (and placebo injections in a blinded fashion) for the duration of Period 2. Subjects failing to achieve low disease activity at Week 22 and 26 at the end of Period 1 received open-label combination therapy during Period 2 regardless of treatment assignment in Period 1.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1032 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Period, Double - Blind Study to Determine the Optimal Protocol for Treatment Initiation With Methotrexate and Adalimumab Combination Therapy in Patients With Early Rheumatoid Arthritis (OPTIMA)
• Study Start Date: December 2006
• Actual Primary Completion Date: July 2010
• Actual Study Completion Date: July 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: ADA+MTX/PBO+MTX (Arm 1); Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2	Biological: adalimumab; Adalimumab 40 mg/0.8 mL prefilled syringe injected subcutaneously (SC) every other week (eow); Other Names: Humira; D2E7; Drug: methotrexate; Methotrexate 2.5 mg tablets administered orally once a week starting at 7.5 mg/week with dose escalation (weekly or every other week) by 2.5 mg intervals to 20 mg/week.; Biological: placebo; Placebo for adalimumab 0.8 mL prefilled syringe injected subcutaneously (SC) every other week (eow)
Experimental: ADA+MTX/ADA+MTX (Arm2); Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2	Biological: adalimumab; Adalimumab 40 mg/0.8 mL prefilled syringe injected subcutaneously (SC) every other week (eow); Other Names: Humira; D2E7; Drug: methotrexate; Methotrexate 2.5 mg tablets administered orally once a week starting at 7.5 mg/week with dose escalation (weekly or every other week) by 2.5 mg intervals to 20 mg/week.
Experimental: ADA+MTX/OL ADA+MTX (Arm 3); Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA + MTX during Period 2	Biological: adalimumab; Adalimumab 40 mg/0.8 mL prefilled syringe injected subcutaneously (SC) every other week (eow); Other Names: Humira; D2E7; Drug: methotrexate; Methotrexate 2.5 mg tablets administered orally once a week starting at 7.5 mg/week with dose escalation (weekly or every other week) by 2.5 mg intervals to 20 mg/week.
Experimental: PBO+MTX/PBO+MTX (Arm 4); Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2	Drug: methotrexate; Methotrexate 2.5 mg tablets administered orally once a week starting at 7.5 mg/week with dose escalation (weekly or every other week) by 2.5 mg intervals to 20 mg/week.; Biological: placebo; Placebo for adalimumab 0.8 mL prefilled syringe injected subcutaneously (SC) every other week (eow)
Experimental: PBO+MTX/OL ADA+MTX (Arm 5); Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2.	Biological: adalimumab; Adalimumab 40 mg/0.8 mL prefilled syringe injected subcutaneously (SC) every other week (eow); Other Names: Humira; D2E7; Drug: methotrexate; Methotrexate 2.5 mg tablets administered orally once a week starting at 7.5 mg/week with dose escalation (weekly or every other week) by 2.5 mg intervals to 20 mg/week.; Biological: placebo; Placebo for adalimumab 0.8 mL prefilled syringe injected subcutaneously (SC) every other week (eow)

Outcome Measures

Primary Outcome Measures :

1. Number of Subjects With Low Disease Activity (DAS28 Less Than 3.2) and No Radiographic Progression From Baseline (Change in mTSS Less Than or Equal to 0.5) at Week 78, Arm 2 vs. Arm 4 [ Time Frame: Week 78 ]
   The Disease Activity Score (DAS28) is calculated using the number of tender and swollen joints (out of 28 counted), C-reactive protein level, and the patient's global assessment of disease activity. The calculated range of DAS28 is 0.49 to 9.07, with scores below 3.2 indicating low disease activity. For the modified Total Sharp score (mTSS), x-rays of hand/wrist and feet joints are scored for erosions (0 to 5) and joint space narrowing (0 to 4). The erosion score and the narrowing score are added to determine the total score, which ranges from 0 (no damage) to 448.

Secondary Outcome Measures :

1. Number of Subjects With Low Disease Activity (DAS28 Less Than 3.2) and No Radiographic Progression From Baseline (Change in mTSS Less Than or Equal to 0.5) at Week 78, Arm 2 vs. Arm 1 [ Time Frame: Week 78 ]
   The Disease Activity Score (DAS28) is calculated using the number of tender and swollen joints (out of 28 counted), C-reactive protein level, and the patient's global assessment of disease activity. The calculated range of DAS28 is 0.49 to 9.07, with scores below 3.2 indicating low disease activity. For the modified Total Sharp score (mTSS), x-rays of hand/wrist and feet joints are scored for erosions (0 to 5) and joint space narrowing (0 to 4). The erosion score and the narrowing score are added to determine the total score, which ranges from 0 (no damage) to 448.
2. Number of Subjects With DAS28 Low Disease Activity (DAS28 Less Than 3.2) at Week 78 [ Time Frame: Week 78 ]
   The Disease Activity Score (DAS28) is calculated using the number of tender and swollen joints (out of 28 counted), C-reactive protein level, and the patient's global assessment of disease activity. The calculated range of DAS28 is 0.49 to 9.07. A DAS28 less than 2.6 indicates clinical remission, DAS28 2.6 to 3.2 indicates low disease activity, DAS28 3.2 to less than 5.1 indicates moderate disease activity, and DAS28 of 5.1 or greater indicates high disease activity.
3. Number of Subjects With DAS28 Remission (DAS28 Less Than 2.6) at Week 78 [ Time Frame: Week 78 ]
   The Disease Activity Score (DAS28) is calculated using the number of tender and swollen joints (out of 28 counted), C-reactive protein level, and the patient's global assessment of disease activity. The calculated range of DAS28 is 0.49 to 9.07. A DAS28 less than 2.6 indicates clinical remission, DAS28 2.6 to 3.2 indicates low disease activity, DAS28 3.2 to less than 5.1 indicates moderate disease activity, and DAS28 of 5.1 or greater indicates high disease activity.
4. Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS Less Than or Equal to 0.5) at Week 78 [ Time Frame: Week 78 ]
   For the modified Total Sharp score (mTSS), x-rays of hand/wrist and feet joints are scored for erosions (0 to 5) and joint space narrowing (0 to 4). The erosion score and the narrowing score are added to determine the total score, which ranges from 0 (no damage) to 448. An increase in mTSS from baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement.
5. Number of Subjects Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 78 [ Time Frame: Week 78 ]
   Subjects were responders if they had greater than or equal to 20% improvement in tender joint count; greater than or equal to 20% improvement in swollen joint count; and greater than or equal to 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).
6. Number of Subjects Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 78 [ Time Frame: Week 78 ]
   Subjects were responders if they had: greater than or equal to 50% improvement in tender joint count; greater than or equal to 50% improvement in swollen joint count; and greater than or equal to 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 Subjects Meeting American College of Rheumatology 70% (ACR70) Response Criteria at Week 78 [ Time Frame: Week 78 ]
   Subjects were responders if they had: greater than or equal to 70% improvement in tender joint count; greater than or equal to 70% improvement in swollen joint count; and greater than or equal to 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. Change From Baseline in DAS28 Score at Week 78 [ Time Frame: Baseline to Week 78 ]
   The Disease Activity Score (DAS28) is calculated using the number of tender and swollen joints (out of 28 counted), C-reactive protein level, and the patient's global assessment of disease activity. The calculated range of DAS28 is 0.49 to 9.07. A DAS28 less than 2.6 indicates clinical remission, DAS28 2.6 to 3.2 indicates low disease activity, DAS28 3.2 to less than 5.1 indicates moderate disease activity, and DAS28 of 5.1 or greater indicates high disease activity.
9. Number of Subjects With Clinical Disease Activity Index (CDAI) Low Disease Activity (CDAI Less Than or Equal to 10) at Week 78 [ Time Frame: Week 78 ]
   The CDAI is calculated using number of swollen joints (28 joints assessed), number of tender joints (28 joints assessed), patient's global assessment of disease activity, and physician's global assessment of disease activity. Scores range from 0 to 76.0, with a higher score reflecting worsening disease.
10. Number of Subjects With Simplified Disease Activity Index (SDAI) Low Disease Activity (SDAI Less Than or Equal to 11) at Week 78 [ Time Frame: Week 78 ]
    The SDAI is calculated using number of swollen joints (28 joints assessed), number of tender joints (28 joints assessed), patient's global assessment of disease activity, physician's global assessment of disease activity, and acute phase reactant (C-reactive protein). Scores range from 0.1 to 86.0, with a higher score reflecting worsening disease.
11. Number of Subjects With Clinical Disease Activity Index (CDAI) Remission (CDAI Less Than or Equal to 2.8) at Week 78 [ Time Frame: Week 78 ]
    The CDAI is calculated using number of swollen joints (28 joints assessed), number of tender joints (28 joints assessed), patient's global assessment of disease activity, and physician's global assessment of disease activity. Scores range from 0 to 76.0, with a higher score reflecting worsening disease.
12. Number of Subjects With Simplified Disease Activity Index (SDAI) Remission (SDAI Less Than or Equal to 3.3) at Week 78 [ Time Frame: Week 78 ]
    The SDAI is calculated using number of swollen joints (28 joints assessed), number of tender joints (28 joints assessed), patient's global assessment of disease activity, physician's global assessment of disease activity, and acute phase reactant (C-reactive protein). Scores range from 0.1 to 86.0, with a higher score reflecting worsening disease.
13. Change From Baseline in CDAI Score at Week 78 [ Time Frame: Baseline to Week 78 ]
    The CDAI is calculated using number of swollen joints (28 joints assessed), number of tender joints (28 joints assessed), patient's global assessment of disease activity, and physician's global assessment of disease activity. Scores range from 0 to 76.0, with a higher score reflecting worsening disease.
14. Change From Baseline in SDAI Score at Week 78 [ Time Frame: Baseline to Week 78 ]
    The SDAI is calculated using number of swollen joints (28 joints assessed), number of tender joints (28 joints assessed), patient's global assessment of disease activity, physician's global assessment of disease activity, and acute phase reactant (C-reactive protein). Scores range from 0.1 to 86.0, with a higher score reflecting worsening disease.
15. Change From Baseline in Synovitis Score According to the Rheumatoid Arthritis Magnetic Resonance Imaging (RA MRI) Scoring System (RAMRIS) at Week 78 [ Time Frame: Baseline to Week 78 ]
    Synovitis was assessed using high-field magnetic resonance imaging (MRI) of the hand and wrist. Images were read and scored according to the Outcomes Measures in Rheumatology Clinical Trials' Rheumatoid Arthritis MRI Scoring System (OMERACT RAMRIS). Synovitis in the wrist and finger joints in the most affected hand was scored from 0 (normal) to 3 (severe), for a maximum total score of 21.
16. Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5) and Normal Function (HAQ-DI Less Than 0.5) at Week 78 [ Time Frame: Week 78 ]
    In the Health Assessment Questionnaire Disability Index (HAQ-DI), participants rated their ability to perform daily tasks on a scale of 0 (without any difficulty) to 3 (unable to do). A mean score of 0-1 represents mild to moderate functional disability, 1-2 represents moderate to severe, 2-3 severe to very severe disability. For the modified Total Sharp score (mTSS), x-rays of hand/wrist and feet joints are scored for erosions (0 to 5) and joint space narrowing (0 to 4). The erosion score and the narrowing score are added to determine the total score, which ranges from 0 (no damage) to 448.
17. Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5), Normal Function (HAQ-DI Less Than or Equal to 0.5), and ACR70 Response at Week 78 [ Time Frame: Week 78 ]
    In the Health Assessment Questionnaire Disability Index (HAQ-DI), a score of 0-1 represents mild to moderate, 1-2 moderate to severe, 2-3 severe to very severe disability. The modified Total Sharp score (mTSS) ranges from 0 (no joint damage) to 448 (worst joint damage). American College of Rheumatology 70% (ACR70) response indicates at least 70% improvement in tender and swollen joint counts and 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; HAQ-DI; and C-reactive protein.
18. Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5), Normal Function (HAQ-DI Less Than 0.5), and DAS28 Remission (DAS28 Less Than 2.6) at Week 78 [ Time Frame: Week 78 ]
    In the Health Assessment Questionnaire Disability Index (HAQ-DI), a score of 0-1 represents mild to moderate, 1-2 moderate to severe, 2-3 severe to very severe disability. The modified Total Sharp score (mTSS) ranges from 0 (no joint damage) to 448 (severe joint damage). The Disease Activity Score (DAS28) ranges from 0.49 to 9.07, with scores less than 2.6 indicating clinical remission.

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

• Subject must be 18 or older and in good health
• Subject must meet the definition of early rheumatoid arthritis (RA) defined by the 1987-revised American College of Rheumatology (ACR) classification criteria and had disease duration of less than 1 year from diagnosis
• Subject must have a Disease Activity Score (DAS28, based on C-reactive protein) greater than 3.2, at least 6 swollen joints out of the 66 assessed, and at least 8 tender joints out of the 68 assessed

• Subject must fulfill at least one of the following three criteria:

  • Rheumatoid factor positive
  • Greater than 1 joint erosion
  • Anti-cyclic citrullinated peptide (CCP) antibody positive.

Exclusion Criteria

• Subject has previously received systemic anti-tumor necrosis factor (TNF) therapy
• Subject has received any biologic or investigational therapy within 6 weeks prior to Baseline
• Subject has been previously treated with more than 2 disease-modifying antirheumatic drugs (DMARDs) or MTX, had been treated with intra-articular or parenteral administration of corticosteroids in preceding 4 weeks, or had undergone joint surgery within the preceding 2 months at joints to be assessed during the study.

Contacts and Locations

Locations

United States, Alabama

Site Reference ID/Investigator# 4560

Birmingham, Alabama, United States, 35205

Site Reference ID/Investigator# 4547

Birmingham, Alabama, United States, 35294-7201

Site Reference ID/Investigator# 6222

Huntsville, Alabama, United States, 35801

Site Reference ID/Investigator# 4537

Mobile, Alabama, United States, 36608

Site Reference ID/Investigator# 6758

Tuscaloosa, Alabama, United States, 35406

United States, California

Site Reference ID/Investigator# 9323

Hemet, California, United States, 92543

Site Reference ID/Investigator# 4568

La Jolla, California, United States, 92037-0943

Site Reference ID/Investigator# 4535

Palm Desert, California, United States, 92260

Site Reference ID/Investigator# 4571

Santa Monica, California, United States, 90404

Site Reference ID/Investigator# 9271

Torrance, California, United States, 90505

Site Reference ID/Investigator# 10746

Victorville, California, United States, 92395

United States, Colorado

Site Reference ID/Investigator# 4559

Denver, Colorado, United States, 80230

United States, Florida

Site Reference ID/Investigator# 6229

Aventura, Florida, United States, 33180

Site Reference ID/Investigator# 10603

Lake Mary, Florida, United States, 32746

Site Reference ID/Investigator# 9325

Orange Park, Florida, United States, 32073

Site Reference ID/Investigator# 4550

Palm Harbor, Florida, United States, 34684

Site Reference ID/Investigator# 4570

Sarasota, Florida, United States, 34239

Site Reference ID/Investigator# 4601

Tampa, Florida, United States, 33614

Site Reference ID/Investigator# 4552

Vero Beach, Florida, United States, 32960

United States, Idaho

Site Reference ID/Investigator# 10745

Meridian, Idaho, United States, 83642

United States, Illinois

Site Reference ID/Investigator# 4548

Chicago, Illinois, United States, 60612

Site Reference ID/Investigator# 4557

Springfield, Illinois, United States, 62704

United States, Kansas

Site Reference ID/Investigator# 4605

Wichita, Kansas, United States, 67203

United States, Maryland

Site Reference ID/Investigator# 10741

Wheaton, Maryland, United States, 20902

United States, Massachusetts

Site Reference ID/Investigator# 6417

Fall River, Massachusetts, United States, 02720

United States, New Hampshire

Site Reference ID/Investigator# 4561

Dover, New Hampshire, United States, 03820

United States, New Jersey

Site Reference ID/Investigator# 11222

Freehold, New Jersey, United States, 07728

Site Reference ID/Investigator# 6228

Passaic, New Jersey, United States, 07055

United States, New Mexico

Site Reference ID/Investigator# 4544

Albuquerque, New Mexico, United States, 87102

United States, New York

Site Reference ID/Investigator# 12821

Bronx, New York, United States, 10461

Site Reference ID/Investigator# 4534

Orchard Park, New York, United States, 14127

Site Reference ID/Investigator# 9324

Plainview, New York, United States, 11803

Site Reference ID/Investigator# 4600

Smithtown, New York, United States, 11787

United States, Ohio

Site Reference ID/Investigator# 4549

Mayfield Village, Ohio, United States, 44143

United States, Oregon

Site Reference ID/Investigator# 6227

Bend, Oregon, United States, 97701

United States, Pennsylvania

Site Reference ID/Investigator# 4546

Duncansville, Pennsylvania, United States, 16635

Site Reference ID/Investigator# 4564

West Reading, Pennsylvania, United States, 19611-1124

Site Reference ID/Investigator# 4558

Wexford, Pennsylvania, United States, 15090

United States, South Carolina

Site Reference ID/Investigator# 4533

Charleston, South Carolina, United States, 29406

Site Reference ID/Investigator# 7482

Greenville, South Carolina, United States, 29601

United States, Tennessee

Site Reference ID/Investigator# 10743

Jackson, Tennessee, United States, 38305

Site Reference ID/Investigator# 4562

Nashville, Tennessee, United States, 37205

United States, Texas

Site Reference ID/Investigator# 4536

Dallas, Texas, United States, 75231

Site Reference ID/Investigator# 4538

Houston, Texas, United States, 77074

Site Reference ID/Investigator# 6899

San Antonio, Texas, United States, 78217

Site Reference ID/Investigator# 6381

Tyler, Texas, United States, 75701

United States, Washington

Site Reference ID/Investigator# 10744

Seattle, Washington, United States, 98133

United States, Wisconsin

Site Reference ID/Investigator# 4545

Glendale, Wisconsin, United States, 53217

Site Reference ID/Investigator# 4572

Oak Creek, Wisconsin, United States, 53154

Argentina

Site Reference ID/Investigator# 3886

Buenos Aires, Argentina, 1426AAL

Site Reference ID/Investigator# 3888

Buenos Aires, Argentina, C1015ABO

Site Reference ID/Investigator# 6346

Buenos Aires, Argentina, C1055AAF

Site Reference ID/Investigator# 3887

Quilmes, Argentina

Site Reference ID/Investigator# 3889

San Miguel de Tucuman, Argentina, T4000AXL

Australia

Site Reference ID/Investigator# 8380

Campsie, Sydney, Australia, 2194

Site Reference ID/Investigator# 6954

Clayton, Australia, 3168

Site Reference ID/Investigator# 6940

Malvern East, Australia, 3145

Austria

Site Reference ID/Investigator# 3915

Graz, Austria, 8036

Site Reference ID/Investigator# 3911

Graz, Austria, A-8020

Site Reference ID/Investigator# 3880

Vienna, Austria, 1090

Site Reference ID/Investigator# 3885

Vienna, Austria, 1100

Site Reference ID/Investigator# 3916

Vienna, Austria, 1130

Site Reference ID/Investigator# 7792

Vienna, Austria, 1160

Belgium

Site Reference ID/Investigator# 3914

Brussels, Belgium, 1200

Site Reference ID/Investigator# 3909

Genk, Belgium, 3600

Site Reference ID/Investigator# 3881

Gilly, Belgium, 6060

Site Reference ID/Investigator# 3376

Liege, Belgium, 4000

Site Reference ID/Investigator# 6720

Mechelen, Belgium, 2800

Site Reference ID/Investigator# 6718

Sint-Niklaas, Belgium, 9100

Site Reference ID/Investigator# 3910

Yvoir, Belgium, 5530

Canada

Site Reference ID/Investigator# 6701

Burlington, Canada, L7R 1E2

Site Reference ID/Investigator# 6834

Edmonton, Canada, T5M 0H4

Site Reference ID/Investigator# 7197

Halifax, Canada, B3H 4K4

Site Reference ID/Investigator# 3883

Hamilton, Canada, L8N 1Y2

Site Reference ID/Investigator# 3884

Hamilton, Canada, L8N 2B6

Site Reference ID/Investigator# 3907

Montreal, Canada, H2L 1S6

Site Reference ID/Investigator# 3903

Montreal, Canada, H3Z 2Z3

Site Reference ID/Investigator# 5178

Ottawa, Canada, K2G 6E2

Site Reference ID/Investigator# 3904

Richmond, Canada, V7C 5L9

Site Reference ID/Investigator# 3912

Sainte-Foy, Quebec, Canada, G1W 4R4

Site Reference ID/Investigator# 3901

Sarnia, Canada, N7T 5W6

Site Reference ID/Investigator# 3906

St. John's, Canada, A1A 5E8

Site Reference ID/Investigator# 6542

Toronto, Canada, M9B 1B1

Site Reference ID/Investigator# 3882

Victoria, Canada, V8V 3P9

Site Reference ID/Investigator# 5616

Windsor, Canada, N8X 5A6

Site Reference ID/Investigator# 5847

Winnipeg, Canada, R3A 1M3

Site Reference ID/Investigator# 3905

Winnipeg, Canada, R3A 1M4

Czech Republic

Site Reference ID/Investigator# 3968

Brno, Czech Republic, 65691

Site Reference ID/Investigator# 3971

Hradec Kralove, Czech Republic, 500 05

Site Reference ID/Investigator# 5559

Ostrava, Czech Republic, 72200

Site Reference ID/Investigator# 3969

Prague 2, Czech Republic, 128 50

Site Reference ID/Investigator# 5548

Uherske Hradiste, Czech Republic, 686 01

France

Site Reference ID/Investigator# 3982

Amiens, France, 80054

Site Reference ID/Investigator# 3979

Le Mans, France, 72037

Site Reference ID/Investigator# 3983

Paris Cedex 14, France, 75679

Site Reference ID/Investigator# 3918

Strasbourg, France, 67098

Germany

Site Reference ID/Investigator# 3926

Bad Nauheim, Germany, D-61231

Site Reference ID/Investigator# 3928

Berlin-Buch, Germany, 13125

Site Reference ID/Investigator# 3978

Damp, Germany, 24351

Site Reference ID/Investigator# 3924

Duesseldorf, Germany, 40225

Site Reference ID/Investigator# 3927

Frankfurt/Main, Germany, 60596

Site Reference ID/Investigator# 3965

Frankfurt, Germany, 60590

Site Reference ID/Investigator# 3925

Freiburg, Germany, 79106

Site Reference ID/Investigator# 4291

Halle, Germany, 06120

Site Reference ID/Investigator# 8489

Hofheim, Germany, D-65719

Site Reference ID/Investigator# 3923

Munich, Germany, 80336

Site Reference ID/Investigator# 8483

Osnabrueck, Germany, D-49074

Site Reference ID/Investigator# 8486

Ratingen, Germany, 40882

Site Reference ID/Investigator# 3919

Vogelsang-Gommern, Germany, 39245

Site Reference ID/Investigator# 6637

Zerbst, Germany, 39261

Hungary

Site Reference ID/Investigator# 3921

Budapest, Hungary, 1023

Site Reference ID/Investigator# 3922

Budapest, Hungary, 1277

Site Reference ID/Investigator# 3920

Debrecen, Hungary, 4012

Mexico

Site Reference ID/Investigator# 3824

Aguascallentes, Mexico, 20230

Site Reference ID/Investigator# 3822

Leon, Guanajuato, Mexico, 37000

Site Reference ID/Investigator# 3825

Mexico City, Mexico, 10700

Site Reference ID/Investigator# 3951

Mexico City, Mexico, 10700

Site Reference ID/Investigator# 3890

Mexico City, Mexico, 14389

Site Reference ID/Investigator# 3823

Mexico City, Mexico, CP 1300

Site Reference ID/Investigator# 3891

Mexico City, Mexico, CP 14050

Netherlands

Site Reference ID/Investigator# 3947

Arnem, Netherlands, 6815 AD

Site Reference ID/Investigator# 3948

Hilversum, Netherlands, 1213XZ

New Zealand

Site Reference ID/Investigator# 8485

Auckland 6, New Zealand

Site Reference ID/Investigator# 8488

Hamilton, New Zealand

Site Reference ID/Investigator# 8496

Timaru, New Zealand

Site Reference ID/Investigator# 8511

Wellington, New Zealand

Norway

Site Reference ID/Investigator# 7607

Alesund, Norway, N-6026

Site Reference ID/Investigator# 7935

Kristiansand S, Norway, 4615

Site Reference ID/Investigator# 7506

Levanger, Norway, 7600

Site Reference ID/Investigator# 7511

Lillehammer, Norway, N-2609

Site Reference ID/Investigator# 7500

Trondheim, Norway, N-7006

Poland

Site Reference ID/Investigator# 3963

Bydgoszcz, Poland, 85168

Site Reference ID/Investigator# 3962

Katowice, Poland, 40635

Site Reference ID/Investigator# 5560

Lublin, Poland, 20954

Site Reference ID/Investigator# 3961

Wroclaw, Poland, 53-342

Puerto Rico

Site Reference ID/Investigator# 3944

Caguas, Puerto Rico, 00725

Site Reference ID/Investigator# 3937

Ponce, Puerto Rico, 00716

Site Reference ID/Investigator# 3934

San Juan, Puerto Rico, 00918

Site Reference ID/Investigator# 3935

San Juan, Puerto Rico, 00936-5067

Slovakia

Site Reference ID/Investigator# 3959

Piestany, Slovakia, 92112

Site Reference ID/Investigator# 3960

Piestany, Slovakia, 92112

South Africa

Site Reference ID/Investigator# 7177

Berea, Durban, South Africa, 4001

Site Reference ID/Investigator# 7175

Cape Town, South Africa, 7405

Site Reference ID/Investigator# 7178

Cape Town, South Africa, 7500

Site Reference ID/Investigator# 7176

Port Elizabeth, South Africa, 6045

Site Reference ID/Investigator# 7172

Pretoria, South Africa, 0028

Site Reference ID/Investigator# 7174

Soweto, South Africa, 2013

Spain

Site Reference ID/Investigator# 3955

A Coruna, Spain, 15006

Site Reference ID/Investigator# 13661

Bilbao, Spain, 48013

Site Reference ID/Investigator# 3930

Elche (Alicante), Spain, 03203

Site Reference ID/Investigator# 8524

Madrid, Spain, 28006

Site Reference ID/Investigator# 3956

Madrid, Spain, 28007

Site Reference ID/Investigator# 3943

Madrid, Spain, 28034

Site Reference ID/Investigator# 3931

Madrid, Spain, 28046

Site Reference ID/Investigator# 3957

Oviedo, Spain, 33006

Site Reference ID/Investigator# 3954

Santiago de Compostela, Spain, 15706

Site Reference ID/Investigator# 3932

Zaragoza, Spain, 50009

Sweden

Site Reference ID/Investigator# 4015

Eskilstuna, Sweden, SE-631 88

Site Reference ID/Investigator# 3984

Falun, Sweden, SE-79182

Site Reference ID/Investigator# 4016

Malmoe, Sweden, 20502

Site Reference ID/Investigator# 4014

Stockholm, Sweden, 171 76

Site Reference ID/Investigator# 4017

Uppsala, Sweden, 75185

United Kingdom

Site Reference ID/Investigator# 4012

Bath, United Kingdom, BA1 1RL

Site Reference ID/Investigator# 8495

Huddersfield, United Kingdom, HD3 3EA

Site Reference ID/Investigator# 4048

Leeds, United Kingdom, LS7 4SA

Site Reference ID/Investigator# 4013

London, United Kingdom, SE1 9RT

Site Reference ID/Investigator# 4046

Newcastle upon Tyne, United Kingdom, NE7 7DN

Site Reference ID/Investigator# 4047

Oxford, United Kingdom, OX3 7LD

Site Reference ID/Investigator# 3985

Southampton, United Kingdom, S016 6YD

Site Reference ID/Investigator# 7977

York, United Kingdom, YO31 8HE

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.

Smolen JS, van Vollenhoven RF, Florentinus S, Chen S, Suboticki JL, Kavanaugh A. Predictors of disease activity and structural progression after treatment with adalimumab plus methotrexate or continued methotrexate monotherapy in patients with early rheumatoid arthritis and suboptimal response to methotrexate. Ann Rheum Dis. 2018 Nov;77(11):1566-1572. doi: 10.1136/annrheumdis-2018-213502. Epub 2018 Aug 3.

Kavanaugh A, van Vollenhoven RF, Fleischmann R, Emery P, Sainsbury I, Florentinus S, Chen S, Guerette B, Kupper H, Smolen JS. Testing treat-to-target outcomes with initial methotrexate monotherapy compared with initial tumour necrosis factor inhibitor (adalimumab) plus methotrexate in early rheumatoid arthritis. Ann Rheum Dis. 2018 Feb;77(2):289-292. doi: 10.1136/annrheumdis-2017-211871. Epub 2017 Nov 16.

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.

Smolen JS, Emery P, Fleischmann R, van Vollenhoven RF, Pavelka K, Durez P, Guerette B, Kupper H, Redden L, Arora V, Kavanaugh A. Adjustment of therapy in rheumatoid arthritis on the basis of achievement of stable low disease activity with adalimumab plus methotrexate or methotrexate alone: the randomised controlled OPTIMA trial. Lancet. 2014 Jan 25;383(9914):321-32. doi: 10.1016/S0140-6736(13)61751-1. Epub 2013 Oct 26. Erratum In: Lancet. 2014 Jan 25;383(9914):308.

• Responsible Party: Abbott
• ClinicalTrials.gov Identifier: NCT00420927
• Other Study ID Numbers: M06-810; 2006-004139-31 ( EudraCT Number )
• First Posted: January 11, 2007
• Results First Posted: September 29, 2011
• Last Update Posted: April 18, 2012
• Last Verified: April 2012

Keywords provided by Abbott:

Early Rheumatoid Arthritis; Tumor Necrosis Factor Optimization

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Adalimumab; Methotrexate; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Physiological Effects of Drugs; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Dermatologic Agents; Enzyme Inhibitors; Folic Acid Antagonists; Immunosuppressive Agents; Immunologic Factors; Antirheumatic Agents; Nucleic Acid Synthesis Inhibitors; Tumor Necrosis Factor Inhibitors; Anti-Inflammatory Agents