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

Primary Purpose

Rheumatoid Arthritis

Status

Completed

Phase

Phase 4

Locations

International

Study Type

Interventional

Intervention

adalimumab

methotrexate

placebo

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Early Rheumatoid Arthritis, Tumor Necrosis Factor Optimization

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

ADA+MTX/PBO+MTX (Arm 1)

ADA+MTX/ADA+MTX (Arm2)

ADA+MTX/OL ADA+MTX (Arm 3)

PBO+MTX/PBO+MTX (Arm 4)

PBO+MTX/OL ADA+MTX (Arm 5)

Arm Description

Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2

Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2

Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA + MTX during Period 2

Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2

Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2.

Outcomes

Primary Outcome Measures

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

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

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

Number of Subjects With DAS28 Low Disease Activity (DAS28 Less Than 3.2) at 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.

Number of Subjects With DAS28 Remission (DAS28 Less Than 2.6) at 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.

Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS Less Than or Equal to 0.5) at 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.

Number of Subjects Meeting American College of Rheumatology 20% (ACR20) Response Criteria at 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).

Number of Subjects Meeting American College of Rheumatology 50% (ACR50) Response Criteria at 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).

Number of Subjects Meeting American College of Rheumatology 70% (ACR70) Response Criteria at 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).

Change From Baseline in DAS28 Score at 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.

Number of Subjects With Clinical Disease Activity Index (CDAI) Low Disease Activity (CDAI Less Than or Equal to 10) at 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.

Number of Subjects With Simplified Disease Activity Index (SDAI) Low Disease Activity (SDAI Less Than or Equal to 11) at 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.

Number of Subjects With Clinical Disease Activity Index (CDAI) Remission (CDAI Less Than or Equal to 2.8) at Week 78

Number of Subjects With Simplified Disease Activity Index (SDAI) Remission (SDAI Less Than or Equal to 3.3) at Week 78

Change From Baseline in CDAI Score at Week 78

Change From Baseline in SDAI Score at Week 78

Change From Baseline in Synovitis Score According to the Rheumatoid Arthritis Magnetic Resonance Imaging (RA MRI) Scoring System (RAMRIS) at 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.

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

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.

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

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.

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

Full Information

NCT ID

NCT00420927

First Posted

January 9, 2007

Last Updated

April 16, 2012

Sponsor

Abbott

1. Study Identification

Unique Protocol Identification Number

NCT00420927

Brief Title

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

Acronym

OPTIMA

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 Type

Interventional

2. Study Status

Record Verification Date

April 2012

Overall Recruitment Status

Completed

Study Start Date

December 2006 (undefined)

Primary Completion Date

July 2010 (Actual)

Study Completion Date

July 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Abbott

4. Oversight

Data Monitoring Committee

5. 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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rheumatoid Arthritis

Keywords

Early Rheumatoid Arthritis, Tumor Necrosis Factor Optimization

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

1032 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ADA+MTX/PBO+MTX (Arm 1)

Arm Type

Experimental

Arm Description

Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2

Arm Title

ADA+MTX/ADA+MTX (Arm2)

Arm Type

Experimental

Arm Description

Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2

Arm Title

ADA+MTX/OL ADA+MTX (Arm 3)

Arm Type

Experimental

Arm Description

Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA + MTX during Period 2

Arm Title

PBO+MTX/PBO+MTX (Arm 4)

Arm Type

Experimental

Arm Description

Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2

Arm Title

PBO+MTX/OL ADA+MTX (Arm 5)

Arm Type

Experimental

Arm Description

Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2.

Intervention Type

Biological

Intervention Name(s)

adalimumab

Other Intervention Name(s)

Humira, D2E7

Intervention Description

Adalimumab 40 mg/0.8 mL prefilled syringe injected subcutaneously (SC) every other week (eow)

Intervention Type

Drug

Intervention Name(s)

methotrexate

Intervention Description

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.

Intervention Type

Biological

Intervention Name(s)

placebo

Intervention Description

Placebo for adalimumab 0.8 mL prefilled syringe injected subcutaneously (SC) every other week (eow)

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Week 78

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

Week 78

Title

Number of Subjects With DAS28 Low Disease Activity (DAS28 Less Than 3.2) at Week 78

Description

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.

Time Frame

Week 78

Title

Number of Subjects With DAS28 Remission (DAS28 Less Than 2.6) at Week 78

Description

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.

Time Frame

Week 78

Title

Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS Less Than or Equal to 0.5) at Week 78

Description

Time Frame

Week 78

Title

Number of Subjects Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 78

Description

Time Frame

Week 78

Title

Number of Subjects Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 78

Description

Time Frame

Week 78

Title

Number of Subjects Meeting American College of Rheumatology 70% (ACR70) Response Criteria at Week 78

Description

Time Frame

Week 78

Title

Change From Baseline in DAS28 Score at Week 78

Description

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.

Time Frame

Baseline to Week 78

Title

Number of Subjects With Clinical Disease Activity Index (CDAI) Low Disease Activity (CDAI Less Than or Equal to 10) at Week 78

Description

Time Frame

Week 78

Title

Number of Subjects With Simplified Disease Activity Index (SDAI) Low Disease Activity (SDAI Less Than or Equal to 11) at Week 78

Description

Time Frame

Week 78

Title

Number of Subjects With Clinical Disease Activity Index (CDAI) Remission (CDAI Less Than or Equal to 2.8) at Week 78

Description

Time Frame

Week 78

Title

Number of Subjects With Simplified Disease Activity Index (SDAI) Remission (SDAI Less Than or Equal to 3.3) at Week 78

Description

Time Frame

Week 78

Title

Change From Baseline in CDAI Score at Week 78

Description

Time Frame

Baseline to Week 78

Title

Change From Baseline in SDAI Score at Week 78

Description

Time Frame

Baseline to Week 78

Title

Change From Baseline in Synovitis Score According to the Rheumatoid Arthritis Magnetic Resonance Imaging (RA MRI) Scoring System (RAMRIS) at Week 78

Description

Time Frame

Baseline to Week 78

Title

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

Description

Time Frame

Week 78

Title

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

Description

Time Frame

Week 78

Title

Description

Time Frame

Week 78

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Laura Redden, MD, PhD

Organizational Affiliation

Abbott

Official's Role

Study Director

Facility Information:

Facility Name

Site Reference ID/Investigator# 4560

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35205

Country

United States

Facility Name

Site Reference ID/Investigator# 4547

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35294-7201

Country

United States

Facility Name

Site Reference ID/Investigator# 6222

City

Huntsville

State/Province

Alabama

ZIP/Postal Code

35801

Country

United States

Facility Name

Site Reference ID/Investigator# 4537

City

Mobile

State/Province

Alabama

ZIP/Postal Code

36608

Country

United States

Facility Name

Site Reference ID/Investigator# 6758

City

Tuscaloosa

State/Province

Alabama

ZIP/Postal Code

35406

Country

United States

Facility Name

Site Reference ID/Investigator# 9323

City

Hemet

State/Province

California

ZIP/Postal Code

92543

Country

United States

Facility Name

Site Reference ID/Investigator# 4568

City

La Jolla

State/Province

California

ZIP/Postal Code

92037-0943

Country

United States

Facility Name

Site Reference ID/Investigator# 4535

City

Palm Desert

State/Province

California

ZIP/Postal Code

92260

Country

United States

Facility Name

Site Reference ID/Investigator# 4571

City

Santa Monica

State/Province

California

ZIP/Postal Code

90404

Country

United States

Facility Name

Site Reference ID/Investigator# 9271

City

Torrance

State/Province

California

ZIP/Postal Code

90505

Country

United States

Facility Name

Site Reference ID/Investigator# 10746

City

Victorville

State/Province

California

ZIP/Postal Code

92395

Country

United States

Facility Name

Site Reference ID/Investigator# 4559

City

Denver

State/Province

Colorado

ZIP/Postal Code

80230

Country

United States

Facility Name

Site Reference ID/Investigator# 6229

City

Aventura

State/Province

Florida

ZIP/Postal Code

33180

Country

United States

Facility Name

Site Reference ID/Investigator# 10603

City

Lake Mary

State/Province

Florida

ZIP/Postal Code

32746

Country

United States

Facility Name

Site Reference ID/Investigator# 9325

City

Orange Park

State/Province

Florida

ZIP/Postal Code

32073

Country

United States

Facility Name

Site Reference ID/Investigator# 4550

City

Palm Harbor

State/Province

Florida

ZIP/Postal Code

34684

Country

United States

Facility Name

Site Reference ID/Investigator# 4570

City

Sarasota

State/Province

Florida

ZIP/Postal Code

34239

Country

United States

Facility Name

Site Reference ID/Investigator# 4601

City

Tampa

State/Province

Florida

ZIP/Postal Code

33614

Country

United States

Facility Name

Site Reference ID/Investigator# 4552

City

Vero Beach

State/Province

Florida

ZIP/Postal Code

32960

Country

United States

Facility Name

Site Reference ID/Investigator# 10745

City

Meridian

State/Province

Idaho

ZIP/Postal Code

83642

Country

United States

Facility Name

Site Reference ID/Investigator# 4548

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60612

Country

United States

Facility Name

Site Reference ID/Investigator# 4557

City

Springfield

State/Province

Illinois

ZIP/Postal Code

62704

Country

United States

Facility Name

Site Reference ID/Investigator# 4605

City

Wichita

State/Province

Kansas

ZIP/Postal Code

67203

Country

United States

Facility Name

Site Reference ID/Investigator# 10741

City

Wheaton

State/Province

Maryland

ZIP/Postal Code

20902

Country

United States

Facility Name

Site Reference ID/Investigator# 6417

City

Fall River

State/Province

Massachusetts

ZIP/Postal Code

02720

Country

United States

Facility Name

Site Reference ID/Investigator# 4561

City

Dover

State/Province

New Hampshire

ZIP/Postal Code

03820

Country

United States

Facility Name

Site Reference ID/Investigator# 11222

City

Freehold

State/Province

New Jersey

ZIP/Postal Code

07728

Country

United States

Facility Name

Site Reference ID/Investigator# 6228

City

Passaic

State/Province

New Jersey

ZIP/Postal Code

07055

Country

United States

Facility Name

Site Reference ID/Investigator# 4544

City

Albuquerque

State/Province

New Mexico

ZIP/Postal Code

87102

Country

United States

Facility Name

Site Reference ID/Investigator# 12821

City

Bronx

State/Province

New York

ZIP/Postal Code

10461

Country

United States

Facility Name

Site Reference ID/Investigator# 4534

City

Orchard Park

State/Province

New York

ZIP/Postal Code

14127

Country

United States

Facility Name

Site Reference ID/Investigator# 9324

City

Plainview

State/Province

New York

ZIP/Postal Code

11803

Country

United States

Facility Name

Site Reference ID/Investigator# 4600

City

Smithtown

State/Province

New York

ZIP/Postal Code

11787

Country

United States

Facility Name

Site Reference ID/Investigator# 4549

City

Mayfield Village

State/Province

Ohio

ZIP/Postal Code

44143

Country

United States

Facility Name

Site Reference ID/Investigator# 6227

City

Bend

State/Province

Oregon

ZIP/Postal Code

97701

Country

United States

Facility Name

Site Reference ID/Investigator# 4546

City

Duncansville

State/Province

Pennsylvania

ZIP/Postal Code

16635

Country

United States

Facility Name

Site Reference ID/Investigator# 4564

City

West Reading

State/Province

Pennsylvania

ZIP/Postal Code

19611-1124

Country

United States

Facility Name

Site Reference ID/Investigator# 4558

City

Wexford

State/Province

Pennsylvania

ZIP/Postal Code

15090

Country

United States

Facility Name

Site Reference ID/Investigator# 4533

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29406

Country

United States

Facility Name

Site Reference ID/Investigator# 7482

City

Greenville

State/Province

South Carolina

ZIP/Postal Code

29601

Country

United States

Facility Name

Site Reference ID/Investigator# 10743

City

Jackson

State/Province

Tennessee

ZIP/Postal Code

38305

Country

United States

Facility Name

Site Reference ID/Investigator# 4562

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37205

Country

United States

Facility Name

Site Reference ID/Investigator# 4536

City

Dallas

State/Province

Texas

ZIP/Postal Code

75231

Country

United States

Facility Name

Site Reference ID/Investigator# 4538

City

Houston

State/Province

Texas

ZIP/Postal Code

77074

Country

United States

Facility Name

Site Reference ID/Investigator# 6899

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78217

Country

United States

Facility Name

Site Reference ID/Investigator# 6381

City

Tyler

State/Province

Texas

ZIP/Postal Code

75701

Country

United States

Facility Name

Site Reference ID/Investigator# 10744

City

Seattle

State/Province

Washington

ZIP/Postal Code

98133

Country

United States

Facility Name

Site Reference ID/Investigator# 4545

City

Glendale

State/Province

Wisconsin

ZIP/Postal Code

53217

Country

United States

Facility Name

Site Reference ID/Investigator# 4572

City

Oak Creek

State/Province

Wisconsin

ZIP/Postal Code

53154

Country

United States

Facility Name

Site Reference ID/Investigator# 3886

City

Buenos Aires

ZIP/Postal Code

1426AAL

Country

Argentina

Facility Name

Site Reference ID/Investigator# 3888

City

Buenos Aires

ZIP/Postal Code

C1015ABO

Country

Argentina

Facility Name

Site Reference ID/Investigator# 6346

City

Buenos Aires

ZIP/Postal Code

C1055AAF

Country

Argentina

Facility Name

Site Reference ID/Investigator# 3887

City

Quilmes

Country

Argentina

Facility Name

Site Reference ID/Investigator# 3889

City

San Miguel de Tucuman

ZIP/Postal Code

T4000AXL

Country

Argentina

Facility Name

Site Reference ID/Investigator# 8380

City

Campsie, Sydney

ZIP/Postal Code

2194

Country

Australia

Facility Name

Site Reference ID/Investigator# 6954

City

Clayton

ZIP/Postal Code

3168

Country

Australia

Facility Name

Site Reference ID/Investigator# 6940

City

Malvern East

ZIP/Postal Code

3145

Country

Australia

Facility Name

Site Reference ID/Investigator# 3915

City

Graz

ZIP/Postal Code

8036

Country

Austria

Facility Name

Site Reference ID/Investigator# 3911

City

Graz

ZIP/Postal Code

A-8020

Country

Austria

Facility Name

Site Reference ID/Investigator# 3880

City

Vienna

ZIP/Postal Code

1090

Country

Austria

Facility Name

Site Reference ID/Investigator# 3885

City

Vienna

ZIP/Postal Code

1100

Country

Austria

Facility Name

Site Reference ID/Investigator# 3916

City

Vienna

ZIP/Postal Code

1130

Country

Austria

Facility Name

Site Reference ID/Investigator# 7792

City

Vienna

ZIP/Postal Code

1160

Country

Austria

Facility Name

Site Reference ID/Investigator# 3914

City

Brussels

ZIP/Postal Code

1200

Country

Belgium

Facility Name

Site Reference ID/Investigator# 3909

City

Genk

ZIP/Postal Code

3600

Country

Belgium

Facility Name

Site Reference ID/Investigator# 3881

City

Gilly

ZIP/Postal Code

6060

Country

Belgium

Facility Name

Site Reference ID/Investigator# 3376

City

Liege

ZIP/Postal Code

4000

Country

Belgium

Facility Name

Site Reference ID/Investigator# 6720

City

Mechelen

ZIP/Postal Code

2800

Country

Belgium

Facility Name

Site Reference ID/Investigator# 6718

City

Sint-Niklaas

ZIP/Postal Code

9100

Country

Belgium

Facility Name

Site Reference ID/Investigator# 3910

City

Yvoir

ZIP/Postal Code

5530

Country

Belgium

Facility Name

Site Reference ID/Investigator# 6701

City

Burlington

ZIP/Postal Code

L7R 1E2

Country

Canada

Facility Name

Site Reference ID/Investigator# 6834

City

Edmonton

ZIP/Postal Code

T5M 0H4

Country

Canada

Facility Name

Site Reference ID/Investigator# 7197

City

Halifax

ZIP/Postal Code

B3H 4K4

Country

Canada

Facility Name

Site Reference ID/Investigator# 3883

City

Hamilton

ZIP/Postal Code

L8N 1Y2

Country

Canada

Facility Name

Site Reference ID/Investigator# 3884

City

Hamilton

ZIP/Postal Code

L8N 2B6

Country

Canada

Facility Name

Site Reference ID/Investigator# 3907

City

Montreal

ZIP/Postal Code

H2L 1S6

Country

Canada

Facility Name

Site Reference ID/Investigator# 3903

City

Montreal

ZIP/Postal Code

H3Z 2Z3

Country

Canada

Facility Name

Site Reference ID/Investigator# 5178

City

Ottawa

ZIP/Postal Code

K2G 6E2

Country

Canada

Facility Name

Site Reference ID/Investigator# 3904

City

Richmond

ZIP/Postal Code

V7C 5L9

Country

Canada

Facility Name

Site Reference ID/Investigator# 3912

City

Sainte-Foy, Quebec

ZIP/Postal Code

G1W 4R4

Country

Canada

Facility Name

Site Reference ID/Investigator# 3901

City

Sarnia

ZIP/Postal Code

N7T 5W6

Country

Canada

Facility Name

Site Reference ID/Investigator# 3906

City

St. John's

ZIP/Postal Code

A1A 5E8

Country

Canada

Facility Name

Site Reference ID/Investigator# 6542

City

Toronto

ZIP/Postal Code

M9B 1B1

Country

Canada

Facility Name

Site Reference ID/Investigator# 3882

City

Victoria

ZIP/Postal Code

V8V 3P9

Country

Canada

Facility Name

Site Reference ID/Investigator# 5616

City

Windsor

ZIP/Postal Code

N8X 5A6

Country

Canada

Facility Name

Site Reference ID/Investigator# 5847

City

Winnipeg

ZIP/Postal Code

R3A 1M3

Country

Canada

Facility Name

Site Reference ID/Investigator# 3905

City

Winnipeg

ZIP/Postal Code

R3A 1M4

Country

Canada

Facility Name

Site Reference ID/Investigator# 3968

City

Brno

ZIP/Postal Code

65691

Country

Czech Republic

Facility Name

Site Reference ID/Investigator# 3971

City

Hradec Kralove

ZIP/Postal Code

500 05

Country

Czech Republic

Facility Name

Site Reference ID/Investigator# 5559

City

Ostrava

ZIP/Postal Code

72200

Country

Czech Republic

Facility Name

Site Reference ID/Investigator# 3969

City

Prague 2

ZIP/Postal Code

128 50

Country

Czech Republic

Facility Name

Site Reference ID/Investigator# 5548

City

Uherske Hradiste

ZIP/Postal Code

686 01

Country

Czech Republic

Facility Name

Site Reference ID/Investigator# 3982

City

Amiens

ZIP/Postal Code

80054

Country

France

Facility Name

Site Reference ID/Investigator# 3979

City

Le Mans

ZIP/Postal Code

72037

Country

France

Facility Name

Site Reference ID/Investigator# 3983

City

Paris Cedex 14

ZIP/Postal Code

75679

Country

France

Facility Name

Site Reference ID/Investigator# 3918

City

Strasbourg

ZIP/Postal Code

67098

Country

France

Facility Name

Site Reference ID/Investigator# 3926

City

Bad Nauheim

ZIP/Postal Code

D-61231

Country

Germany

Facility Name

Site Reference ID/Investigator# 3928

City

Berlin-Buch

ZIP/Postal Code

13125

Country

Germany

Facility Name

Site Reference ID/Investigator# 3978

City

Damp

ZIP/Postal Code

24351

Country

Germany

Facility Name

Site Reference ID/Investigator# 3924

City

Duesseldorf

ZIP/Postal Code

40225

Country

Germany

Facility Name

Site Reference ID/Investigator# 3927

City

Frankfurt/Main

ZIP/Postal Code

60596

Country

Germany

Facility Name

Site Reference ID/Investigator# 3965

City

Frankfurt

ZIP/Postal Code

60590

Country

Germany

Facility Name

Site Reference ID/Investigator# 3925

City

Freiburg

ZIP/Postal Code

79106

Country

Germany

Facility Name

Site Reference ID/Investigator# 4291

City

Halle

ZIP/Postal Code

06120

Country

Germany

Facility Name

Site Reference ID/Investigator# 8489

City

Hofheim

ZIP/Postal Code

D-65719

Country

Germany

Facility Name

Site Reference ID/Investigator# 3923

City

Munich

ZIP/Postal Code

80336

Country

Germany

Facility Name

Site Reference ID/Investigator# 8483

City

Osnabrueck

ZIP/Postal Code

D-49074

Country

Germany

Facility Name

Site Reference ID/Investigator# 8486

City

Ratingen

ZIP/Postal Code

40882

Country

Germany

Facility Name

Site Reference ID/Investigator# 3919

City

Vogelsang-Gommern

ZIP/Postal Code

39245

Country

Germany

Facility Name

Site Reference ID/Investigator# 6637

City

Zerbst

ZIP/Postal Code

39261

Country

Germany

Facility Name

Site Reference ID/Investigator# 3921

City

Budapest

ZIP/Postal Code

1023

Country

Hungary

Facility Name

Site Reference ID/Investigator# 3922

City

Budapest

ZIP/Postal Code

1277

Country

Hungary

Facility Name

Site Reference ID/Investigator# 3920

City

Debrecen

ZIP/Postal Code

4012

Country

Hungary

Facility Name

Site Reference ID/Investigator# 3824

City

Aguascallentes

ZIP/Postal Code

20230

Country

Mexico

Facility Name

Site Reference ID/Investigator# 3822

City

Leon, Guanajuato

ZIP/Postal Code

37000

Country

Mexico

Facility Name

Site Reference ID/Investigator# 3825

City

Mexico City

ZIP/Postal Code

10700

Country

Mexico

Facility Name

Site Reference ID/Investigator# 3951

City

Mexico City

ZIP/Postal Code

10700

Country

Mexico

Facility Name

Site Reference ID/Investigator# 3890

City

Mexico City

ZIP/Postal Code

14389

Country

Mexico

Facility Name

Site Reference ID/Investigator# 3823

City

Mexico City

ZIP/Postal Code

CP 1300

Country

Mexico

Facility Name

Site Reference ID/Investigator# 3891

City

Mexico City

ZIP/Postal Code

CP 14050

Country

Mexico

Facility Name

Site Reference ID/Investigator# 3947

City

Arnem

ZIP/Postal Code

6815 AD

Country

Netherlands

Facility Name

Site Reference ID/Investigator# 3948

City

Hilversum

ZIP/Postal Code

1213XZ

Country

Netherlands

Facility Name

Site Reference ID/Investigator# 8485

City

Auckland 6

Country

New Zealand

Facility Name

Site Reference ID/Investigator# 8488

City

Hamilton

Country

New Zealand

Facility Name

Site Reference ID/Investigator# 8496

City

Timaru

Country

New Zealand

Facility Name

Site Reference ID/Investigator# 8511

City

Wellington

Country

New Zealand

Facility Name

Site Reference ID/Investigator# 7607

City

Alesund

ZIP/Postal Code

N-6026

Country

Norway

Facility Name

Site Reference ID/Investigator# 7935

City

Kristiansand S

ZIP/Postal Code

4615

Country

Norway

Facility Name

Site Reference ID/Investigator# 7506

City

Levanger

ZIP/Postal Code

7600

Country

Norway

Facility Name

Site Reference ID/Investigator# 7511

City

Lillehammer

ZIP/Postal Code

N-2609

Country

Norway

Facility Name

Site Reference ID/Investigator# 7500

City

Trondheim

ZIP/Postal Code

N-7006

Country

Norway

Facility Name

Site Reference ID/Investigator# 3963

City

Bydgoszcz

ZIP/Postal Code

85168

Country

Poland

Facility Name

Site Reference ID/Investigator# 3962

City

Katowice

ZIP/Postal Code

40635

Country

Poland

Facility Name

Site Reference ID/Investigator# 5560

City

Lublin

ZIP/Postal Code

20954

Country

Poland

Facility Name

Site Reference ID/Investigator# 3961

City

Wroclaw

ZIP/Postal Code

53-342

Country

Poland

Facility Name

Site Reference ID/Investigator# 3944

City

Caguas

ZIP/Postal Code

00725

Country

Puerto Rico

Facility Name

Site Reference ID/Investigator# 3937

City

Ponce

ZIP/Postal Code

00716

Country

Puerto Rico

Facility Name

Site Reference ID/Investigator# 3934

City

San Juan

ZIP/Postal Code

00918

Country

Puerto Rico

Facility Name

Site Reference ID/Investigator# 3935

City

San Juan

ZIP/Postal Code

00936-5067

Country

Puerto Rico

Facility Name

Site Reference ID/Investigator# 3959

City

Piestany

ZIP/Postal Code

92112

Country

Slovakia

Facility Name

Site Reference ID/Investigator# 3960

City

Piestany

ZIP/Postal Code

92112

Country

Slovakia

Facility Name

Site Reference ID/Investigator# 7177

City

Berea, Durban

ZIP/Postal Code

4001

Country

South Africa

Facility Name

Site Reference ID/Investigator# 7175

City

Cape Town

ZIP/Postal Code

7405

Country

South Africa

Facility Name

Site Reference ID/Investigator# 7178

City

Cape Town

ZIP/Postal Code

7500

Country

South Africa

Facility Name

Site Reference ID/Investigator# 7176

City

Port Elizabeth

ZIP/Postal Code

6045

Country

South Africa

Facility Name

Site Reference ID/Investigator# 7172

City

Pretoria

ZIP/Postal Code

0028

Country

South Africa

Facility Name

Site Reference ID/Investigator# 7174

City

Soweto

ZIP/Postal Code

2013

Country

South Africa

Facility Name

Site Reference ID/Investigator# 3955

City

A Coruna

ZIP/Postal Code

15006

Country

Spain

Facility Name

Site Reference ID/Investigator# 13661

City

Bilbao

ZIP/Postal Code

48013

Country

Spain

Facility Name

Site Reference ID/Investigator# 3930

City

Elche (Alicante)

ZIP/Postal Code

03203

Country

Spain

Facility Name

Site Reference ID/Investigator# 8524

City

Madrid

ZIP/Postal Code

28006

Country

Spain

Facility Name

Site Reference ID/Investigator# 3956

City

Madrid

ZIP/Postal Code

28007

Country

Spain

Facility Name

Site Reference ID/Investigator# 3943

City

Madrid

ZIP/Postal Code

28034

Country

Spain

Facility Name

Site Reference ID/Investigator# 3931

City

Madrid

ZIP/Postal Code

28046

Country

Spain

Facility Name

Site Reference ID/Investigator# 3957

City

Oviedo

ZIP/Postal Code

33006

Country

Spain

Facility Name

Site Reference ID/Investigator# 3954

City

Santiago de Compostela

ZIP/Postal Code

15706

Country

Spain

Facility Name

Site Reference ID/Investigator# 3932

City

Zaragoza

ZIP/Postal Code

50009

Country

Spain

Facility Name

Site Reference ID/Investigator# 4015

City

Eskilstuna

ZIP/Postal Code

SE-631 88

Country

Sweden

Facility Name

Site Reference ID/Investigator# 3984

City

Falun

ZIP/Postal Code

SE-79182

Country

Sweden

Facility Name

Site Reference ID/Investigator# 4016

City

Malmoe

ZIP/Postal Code

20502

Country

Sweden

Facility Name

Site Reference ID/Investigator# 4014

City

Stockholm

ZIP/Postal Code

171 76

Country

Sweden

Facility Name

Site Reference ID/Investigator# 4017

City

Uppsala

ZIP/Postal Code

75185

Country

Sweden

Facility Name

Site Reference ID/Investigator# 4012

City

Bath

ZIP/Postal Code

BA1 1RL

Country

United Kingdom

Facility Name

Site Reference ID/Investigator# 8495

City

Huddersfield

ZIP/Postal Code

HD3 3EA

Country

United Kingdom

Facility Name

Site Reference ID/Investigator# 4048

City

Leeds

ZIP/Postal Code

LS7 4SA

Country

United Kingdom

Facility Name

Site Reference ID/Investigator# 4013

City

London

ZIP/Postal Code

SE1 9RT

Country

United Kingdom

Facility Name

Site Reference ID/Investigator# 4046

City

Newcastle upon Tyne

ZIP/Postal Code

NE7 7DN

Country

United Kingdom

Facility Name

Site Reference ID/Investigator# 4047

City

Oxford

ZIP/Postal Code

OX3 7LD

Country

United Kingdom

Facility Name

Site Reference ID/Investigator# 3985

City

Southampton

ZIP/Postal Code

S016 6YD

Country

United Kingdom

Facility Name

Site Reference ID/Investigator# 7977

City

York

ZIP/Postal Code

YO31 8HE

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

31707982

Citation

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.

Results Reference

derived

PubMed Identifier

30076156

Citation

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.

Results Reference

derived

PubMed Identifier

29146743

Citation

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.

Results Reference

derived

PubMed Identifier

29018564

Citation

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.

Results Reference

derived

PubMed Identifier

27338778

Citation

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.

Results Reference

derived

PubMed Identifier

24168956

Citation

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.

Results Reference

derived

Learn more about this trial

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

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

Rheumatoid Arthritis

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial