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

NCT00195702 | Completed Phase 3 Results DMC

• 1 other identifier: DE019
• Study Type: interventional
• Target: 619
• Locations: 2 countries
• Sites: 87

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.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (3)

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

  Week 24

• Change From Baseline in Modified Total Sharp X-ray Score at 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.

  Baseline and Week 52

• Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at 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.

  Baseline and Week 52

Secondary Outcomes (10)

• Number of Participants Meeting ACR20 Response Criteria at Week 52

  Week 52

• Change From Baseline in Modified Total Sharp X-ray Score at Week 24

  Baseline and Week 24

• Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 24

  Baseline and Week 24

• Maintenance of the Disability Index of the HAQ at Week 52 for Participants Who Were Responders at Week 12 or Week 24

  Week 52

• Maintenance of ACR20 Response at Week 52 for Participants Who Were ACR20 Responders at Week 24

  Week 52

Other Outcomes (15)

• Baseline Measure: Gender - Female/Male - for the Any Adalimumab Through Year 10 Group (Intent-to-Treat)

  Baseline for Intent-to-Treat (Any Adalimumab Through Year 10) Group

• Baseline Measure: Age Categories for the Any Adalimumab Through Year 10 Group (Intent-to-Treat)

  Baseline for Intent-to-Treat (Any Adalimumab Through Year 10) Group

• Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 260

  Week 260

Study Arms (6)

DB adalimumab 20 mg ew

EXPERIMENTAL

Subjects received 20 mg adalimumab subcutaneously (SC) once weekly (ew) and concomitant methotrexate (MTX) during the double-blind (DB) phase.

Biological: Adalimumab

DB adalimumab 40 mg eow

EXPERIMENTAL

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

DB placebo ew

PLACEBO COMPARATOR

Subjects received placebo subcutaneously (SC) once weekly (ew) and concomitant methotrexate (MTX) during the double-blind (DB) phase.

Drug: Placebo

DB adalimumab 20 mg ew/OL adalimumab 40 mg eow

EXPERIMENTAL

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

DB adalimumab 40 mg eow/OL adalimumab 40 mg eow

EXPERIMENTAL

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

DB placebo ew/OL adalimumab 40 mg eow

EXPERIMENTAL

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

Interventions

Adalimumab BIOLOGICAL

Self-administered, subcutaneous injection of 20 mg adalimumab (1.6 mL/injection) once weekly (ew) for up to 52 weeks.

Also known as: ABT-D2E7, Humira

DB adalimumab 20 mg ew

Placebo DRUG

Self-administered, subcutaneous injection of placebo (1.6 mL/injection) once weekly (ew) for up to 52 weeks.

DB placebo ew

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 or older and in good health (Investigator discretion) with a recent stable medical history
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Abbott: lead

Study Sites (87)

Site Ref # / Investigator 424

Huntsville, Alabama, 35801, United States

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Site Ref # / Investigator 2510

Mobile, Alabama, 36608, United States

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Site Ref # / Investigator 60729

Phoenix, Arizona, 85012, United States

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Site Ref # / Investigator 725

Scottsdale, Arizona, 85260, United States

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Site Ref # / Investigator 60736

Anaheim, California, 92801, United States

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Site Ref # / Investigator 360

Escondido, California, 92025, United States

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Site Ref # / Investigator 714

La Jolla, California, 92037-0943, United States

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Site Ref # / Investigator 469

La Jolla, California, 92037, United States

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Site Ref # / Investigator 419

Palm Desert, California, 92260, United States

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Site Ref # / Investigator 492

San Jose, California, 95126, United States

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Site Ref # / Investigator 60734

San Louis Obispo, California, 93405, United States

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Site Ref # / Investigator 60739

Van Nuys, California, 91405, United States

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Site Ref # / Investigator 712

Danbury, Connecticut, 06810, United States

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Site Ref # / Investigator 710

Aventura, Florida, 33180, United States

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Site Ref # / Investigator 498

Dunedin, Florida, 34698, United States

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Site Ref # / Investigator 499

Orlando, Florida, 32806, United States

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Site Ref # / Investigator 729

Tampa, Florida, 33614, United States

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Site Ref # / Investigator 463

Zephyrhills, Florida, 33542, United States

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Site Ref # / Investigator 2436

Boise, Idaho, 83704, United States

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Site Ref # / Investigator 485

Idaho Falls, Idaho, 83404, United States

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Site Ref # / Investigator 60732

Chicago, Illinois, 60611, United States

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Site Ref # / Investigator 726

Springfield, Illinois, 62704, United States

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Site Ref # / Investigator 2506

Indianapolis, Indiana, 46260, United States

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Site Ref # / Investigator 732

South Bend, Indiana, 46601, United States

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Site Ref # / Investigator 60730

Shawnee Mission, Kansas, 66216, United States

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Site Ref # / Investigator 467

Wichita, Kansas, 67203, United States

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Site Ref # / Investigator 494

Wichita, Kansas, 67208, United States

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Site Ref # / Investigator 491

Lexington, Kentucky, 40509, United States

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Site Ref # / Investigator 2508

Portland, Maine, 04102, United States

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Site Ref # / Investigator 392

Baltimore, Maryland, 21239, United States

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Site Ref # / Investigator 354

Cumberland, Maryland, 21502, United States

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Site Ref # / Investigator 730

Wheaton, Maryland, 20902, United States

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Site Ref # / Investigator 465

Burlington, Massachusetts, 01805, United States

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Site Ref # / Investigator 2512

Worcester, Massachusetts, 01610, United States

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Site Ref # / Investigator 471

Grand Rapids, Michigan, 49506, United States

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Site Ref # / Investigator 473

Kalamazoo, Michigan, 49009, United States

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Site Ref # / Investigator 731

Kansas City, Missouri, 64114, United States

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Site Ref # / Investigator 502

St Louis, Missouri, 63110, United States

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Site Ref # / Investigator 482

St Louis, Missouri, 63128, United States

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Site Ref # / Investigator 371

St Louis, Missouri, 63141, United States

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Site Ref # / Investigator 487

Omaha, Nebraska, 68114, United States

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Site Ref # / Investigator 353

Concord, New Hampshire, 03301, United States

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Site Ref # / Investigator 364

Dover, New Hampshire, 03820, United States

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Site Ref # / Investigator 60726

Mercerville, New Jersey, 08619, United States

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Site Ref # / Investigator 358

Voorhees Township, New Jersey, 08043, United States

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Site Ref # / Investigator 483

Rochester, New York, 14609, United States

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Site Ref # / Investigator 512

Durham, North Carolina, 27704, United States

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Site Ref # / Investigator 340

Greensboro, North Carolina, 27408, United States

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Site Ref # / Investigator 461

Raleigh, North Carolina, 27609, United States

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Site Ref # / Investigator 500

Raleigh, North Carolina, 27609, United States

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Site Ref # / Investigator 60731

Raleigh, North Carolina, 27612, United States

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Site Ref # / Investigator 60737

Salisbury, North Carolina, 28144, United States

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Site Ref # / Investigator 456

Mayfield Village, Ohio, 44143, United States

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Site Ref # / Investigator 470

Oklahoma City, Oklahoma, 73112, United States

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Site Ref # / Investigator 60723

Oklahoma City, Oklahoma, 73112, United States

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Site Ref # / Investigator 422

Eugene, Oregon, 97401, United States

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Site Ref # / Investigator 60735

Colmar, Pennsylvania, 18915-9671, United States

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Site Ref # / Investigator 2507

Duncansville, Pennsylvania, 16635, United States

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Site Ref # / Investigator 717

East Norriton, Pennsylvania, 19401, United States

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Site Ref # / Investigator 352

Mechanicsburg, Pennsylvania, 17055, United States

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Site Ref # / Investigator 480

Wexford, Pennsylvania, 15090, United States

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Site Ref # / Investigator 2511

Wyomissing, Pennsylvania, 19610, United States

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Site Ref # / Investigator 60724

Wyomissing, Pennsylvania, 19610, United States

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Site Ref # / Investigator 718

Charleston, South Carolina, 29406, United States

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Site Ref # / Investigator 460

Memphis, Tennessee, 38119, United States

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Site Ref # / Investigator 462

Nashville, Tennessee, 37205, United States

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Site Ref # / Investigator 716

Austin, Texas, 78705, United States

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Site Ref # / Investigator 60728

Galveston, Texas, 77555-0759, United States

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Site Ref # / Investigator 2509

Houston, Texas, 77074, United States

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Site Ref # / Investigator 510

Houston, Texas, 77074, United States

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Site Ref # / Investigator 60725

Falls Church, Virginia, 22044, United States

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Site Ref # / Investigator 711

Richmond, Virginia, 23219, United States

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Site Ref # / Investigator 509

Seattle, Washington, 98166-2967, United States

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Site Ref # / Investigator 356

Spokane, Washington, 99204, United States

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Site Ref # / Investigator 464

Tacoma, Washington, 98405, United States

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Site Ref # / Investigator 60738

Kenosha, Wisconsin, 53142, United States

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Site Ref # / Investigator 475

Calgary, Alberta, T2N 4N1, Canada

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Site Ref # / Investigator 495

Penticton, British Columbia, V2A 3G8, Canada

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Site Ref # / Investigator 2496

Richmond, British Columbia, V7C 5L9, Canada

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Site Ref # / Investigator 2495

Winnipeg, Manitoba, R3N OK6, Canada

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Site Ref # / Investigator 496

Halifax, Nova Scotia, B3H 4K4, Canada

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Site Ref # / Investigator 444

Newmarket, Ontario, L3Y 3R7, Canada

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Site Ref # / Investigator 2497

Toronto, Ontario, M4N 3M5, Canada

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Site Ref # / Investigator 478

Toronto, Ontario, M5L 3L9, Canada

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Site Ref # / Investigator 421

Toronto, Ontario, M5T 2S8, Canada

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Site Ref # / Investigator 363

Montreal, Quebec, H3Z 2Z3, Canada

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Site Ref # / Investigator 60702

Saskatoon, Saskatchewan, S7N 0W8, Canada

Location

Related Publications (7)

• 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.

  PMID: 31707982 DERIVED

• 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.

  PMID: 29018564 DERIVED

• 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.

  PMID: 27338778 DERIVED

• 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.

  PMID: 25139667 DERIVED

• 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.

  PMID: 25073879 DERIVED

• 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.

  PMID: 23818718 DERIVED

• 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.

  PMID: 21285171 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Adalimumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Global Medical Services
• Organization: Abbott

800-633-9110

Study Officials

• Laura Redden, MD, PhD

  Abbott

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 20, 2005
• Study Start: February 1, 2000
• Primary Completion: September 1, 2002
• Study Completion: August 1, 2010
• Last Updated: August 26, 2011
• Results First Posted: March 1, 2010

Record last verified: 2011-08

Locations

US (76); CA (11)