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

NCT ID: NCT00195702

Last Updated: 2011-08-26

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

619 participants

Study Classification

INTERVENTIONAL

Study Start Date

2000-02-29

Study Completion Date

2010-08-31

Brief Summary

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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.

Detailed Description

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

Conditions

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Rheumatoid Arthritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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DB adalimumab 20 mg ew

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

Group Type EXPERIMENTAL

Adalimumab

Intervention Type BIOLOGICAL

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

DB adalimumab 40 mg eow

Subjects received 40 mg adalimumab subcutaneously (SC) every other week (eow) and concomitant methotrexate (MTX) during the double-blind (DB) phase. Subjects received placebo injections SC and concomitant MTX on the alternate weeks during the DB phase.

Group Type EXPERIMENTAL

Adalimumab

Intervention Type BIOLOGICAL

Self-administered, subcutaneous injection of 40 mg adalimumab (1.6 mL/injection) every other week (eow) for up to 52 weeks.

DB placebo ew

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

DB adalimumab 20 mg ew/OL adalimumab 40 mg eow

Subjects received adalimumab 20 mg subcutaneously (SC) once weekly (ew) during the double-blind (DB) phase, then adalimumab 40 mg SC every other week (eow) during the open-label (OL) extension phase, along with concomitant methotrexate (MTX).

Group Type EXPERIMENTAL

Adalimumab

Intervention Type BIOLOGICAL

Self-administration, subcutaneous (SC) injection of adalimumab 20 mg (1.6 mL/injection) once weekly (ew) for 52 weeks, followed by self-administration, SC injection of adalimumab 40 mg (0.8 mL/injection) every other week (eow) for up to Week 520.

DB adalimumab 40 mg eow/OL adalimumab 40 mg eow

Subjects received adalimumab 40 mg subcutaneously (SC) every other week (eow) with placebo on alternate weeks during the double-blind (DB) phase, then adalimumab 40 mg SC eow during the open-label (OL) extension phase, along with concomitant methotrexate (MTX).

Group Type EXPERIMENTAL

Adalimumab

Intervention Type BIOLOGICAL

Self-administration, subcutaneous (SC) injection of adalimumab 40 mg (1.6 mL/injection) every other week (eow) (with a placebo 1.6 mL/injection on alternate weeks) for 52 weeks, followed by self-administration, SC injection of adalimumab 40 mg (0.8 mL injection) eow for up to Week 520.

DB placebo ew/OL adalimumab 40 mg eow

Subjects received placebo subcutaneously (SC) once weekly (ew) during the double-blind phase, then adalimumab 40 mg SC every other week (eow) during the open-label (OL) extension phase, along with concomitant methotrexate (MTX).

Group Type EXPERIMENTAL

Adalimumab

Intervention Type BIOLOGICAL

Self-administration, subcutaneous (SC) injection of placebo solution (1.6 mL/injection) once weekly (ew) for 52 weeks, followed by self-administration, SC injection of adalimumab 40 mg (0.8 mL/injection) every other week (eow) for up to Week 520.

Interventions

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Adalimumab

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

Intervention Type BIOLOGICAL

Adalimumab

Self-administered, subcutaneous injection of 40 mg adalimumab (1.6 mL/injection) every other week (eow) for up to 52 weeks.

Intervention Type BIOLOGICAL

Placebo

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

Intervention Type DRUG

Adalimumab

Self-administration, subcutaneous (SC) injection of adalimumab 20 mg (1.6 mL/injection) once weekly (ew) for 52 weeks, followed by self-administration, SC injection of adalimumab 40 mg (0.8 mL/injection) every other week (eow) for up to Week 520.

Intervention Type BIOLOGICAL

Adalimumab

Self-administration, subcutaneous (SC) injection of adalimumab 40 mg (1.6 mL/injection) every other week (eow) (with a placebo 1.6 mL/injection on alternate weeks) for 52 weeks, followed by self-administration, SC injection of adalimumab 40 mg (0.8 mL injection) eow for up to Week 520.

Intervention Type BIOLOGICAL

Adalimumab

Self-administration, subcutaneous (SC) injection of placebo solution (1.6 mL/injection) once weekly (ew) for 52 weeks, followed by self-administration, SC injection of adalimumab 40 mg (0.8 mL/injection) every other week (eow) for up to Week 520.

Intervention Type BIOLOGICAL

Other Intervention Names

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ABT-D2E7 Humira ABT-D2E7 Humira ABT-D2E7 Humira ABT-D2E7 Humira ABT-D2E7 Humira

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

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

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Abbott

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Laura Redden, MD, PhD

Role: STUDY_DIRECTOR

Abbott

Locations

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Site Ref # / Investigator 424

Huntsville, Alabama, United States

Site Status

Site Ref # / Investigator 2510

Mobile, Alabama, United States

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Site Ref # / Investigator 60729

Phoenix, Arizona, United States

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Site Ref # / Investigator 725

Scottsdale, Arizona, United States

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Site Ref # / Investigator 60736

Anaheim, California, United States

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Site Ref # / Investigator 360

Escondido, California, United States

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Site Ref # / Investigator 714

La Jolla, California, United States

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Site Ref # / Investigator 469

La Jolla, California, United States

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Site Ref # / Investigator 419

Palm Desert, California, United States

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Site Ref # / Investigator 492

San Jose, California, United States

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Site Ref # / Investigator 60734

San Louis Obispo, California, United States

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Site Ref # / Investigator 60739

Van Nuys, California, United States

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Site Ref # / Investigator 712

Danbury, Connecticut, United States

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Site Ref # / Investigator 710

Aventura, Florida, United States

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Site Ref # / Investigator 498

Dunedin, Florida, United States

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Site Ref # / Investigator 499

Orlando, Florida, United States

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Site Ref # / Investigator 729

Tampa, Florida, United States

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Site Ref # / Investigator 463

Zephyrhills, Florida, United States

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Site Ref # / Investigator 2436

Boise, Idaho, United States

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Site Ref # / Investigator 485

Idaho Falls, Idaho, United States

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Site Ref # / Investigator 60732

Chicago, Illinois, United States

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Site Ref # / Investigator 726

Springfield, Illinois, United States

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Site Ref # / Investigator 2506

Indianapolis, Indiana, United States

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Site Ref # / Investigator 732

South Bend, Indiana, United States

Site Status

Site Ref # / Investigator 60730

Shawnee Mission, Kansas, United States

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Site Ref # / Investigator 467

Wichita, Kansas, United States

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Site Ref # / Investigator 494

Wichita, Kansas, United States

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Site Ref # / Investigator 491

Lexington, Kentucky, United States

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Site Ref # / Investigator 2508

Portland, Maine, United States

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Site Ref # / Investigator 392

Baltimore, Maryland, United States

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Site Ref # / Investigator 354

Cumberland, Maryland, United States

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Site Ref # / Investigator 730

Wheaton, Maryland, United States

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Site Ref # / Investigator 465

Burlington, Massachusetts, United States

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Site Ref # / Investigator 2512

Worcester, Massachusetts, United States

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Site Ref # / Investigator 471

Grand Rapids, Michigan, United States

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Site Ref # / Investigator 473

Kalamazoo, Michigan, United States

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Site Ref # / Investigator 731

Kansas City, Missouri, United States

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Site Ref # / Investigator 502

St Louis, Missouri, United States

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Site Ref # / Investigator 482

St Louis, Missouri, United States

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Site Ref # / Investigator 371

St Louis, Missouri, United States

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Site Ref # / Investigator 487

Omaha, Nebraska, United States

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Site Ref # / Investigator 353

Concord, New Hampshire, United States

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Site Ref # / Investigator 364

Dover, New Hampshire, United States

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Site Ref # / Investigator 60726

Mercerville, New Jersey, United States

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Site Ref # / Investigator 358

Voorhees Township, New Jersey, United States

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Site Ref # / Investigator 483

Rochester, New York, United States

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Site Ref # / Investigator 512

Durham, North Carolina, United States

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Site Ref # / Investigator 340

Greensboro, North Carolina, United States

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Site Ref # / Investigator 461

Raleigh, North Carolina, United States

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Site Ref # / Investigator 500

Raleigh, North Carolina, United States

Site Status

Site Ref # / Investigator 60731

Raleigh, North Carolina, United States

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Site Ref # / Investigator 60737

Salisbury, North Carolina, United States

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Site Ref # / Investigator 456

Mayfield Village, Ohio, United States

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Site Ref # / Investigator 470

Oklahoma City, Oklahoma, United States

Site Status

Site Ref # / Investigator 60723

Oklahoma City, Oklahoma, United States

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Site Ref # / Investigator 422

Eugene, Oregon, United States

Site Status

Site Ref # / Investigator 60735

Colmar, Pennsylvania, United States

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Site Ref # / Investigator 2507

Duncansville, Pennsylvania, United States

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Site Ref # / Investigator 717

East Norriton, Pennsylvania, United States

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Site Ref # / Investigator 352

Mechanicsburg, Pennsylvania, United States

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Site Ref # / Investigator 480

Wexford, Pennsylvania, United States

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Site Ref # / Investigator 2511

Wyomissing, Pennsylvania, United States

Site Status

Site Ref # / Investigator 60724

Wyomissing, Pennsylvania, United States

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Site Ref # / Investigator 718

Charleston, South Carolina, United States

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Site Ref # / Investigator 460

Memphis, Tennessee, United States

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Site Ref # / Investigator 462

Nashville, Tennessee, United States

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Site Ref # / Investigator 716

Austin, Texas, United States

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Site Ref # / Investigator 60728

Galveston, Texas, United States

Site Status

Site Ref # / Investigator 2509

Houston, Texas, United States

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Site Ref # / Investigator 510

Houston, Texas, United States

Site Status

Site Ref # / Investigator 60725

Falls Church, Virginia, United States

Site Status

Site Ref # / Investigator 711

Richmond, Virginia, United States

Site Status

Site Ref # / Investigator 509

Seattle, Washington, United States

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Site Ref # / Investigator 356

Spokane, Washington, United States

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Site Ref # / Investigator 464

Tacoma, Washington, United States

Site Status

Site Ref # / Investigator 60738

Kenosha, Wisconsin, United States

Site Status

Site Ref # / Investigator 475

Calgary, Alberta, Canada

Site Status

Site Ref # / Investigator 495

Penticton, British Columbia, Canada

Site Status

Site Ref # / Investigator 2496

Richmond, British Columbia, Canada

Site Status

Site Ref # / Investigator 2495

Winnipeg, Manitoba, Canada

Site Status

Site Ref # / Investigator 496

Halifax, Nova Scotia, Canada

Site Status

Site Ref # / Investigator 444

Newmarket, Ontario, Canada

Site Status

Site Ref # / Investigator 2497

Toronto, Ontario, Canada

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Site Ref # / Investigator 478

Toronto, Ontario, Canada

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Site Ref # / Investigator 421

Toronto, Ontario, Canada

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Site Ref # / Investigator 363

Montreal, Quebec, Canada

Site Status

Site Ref # / Investigator 60702

Saskatoon, Saskatchewan, Canada

Site Status

Countries

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United States Canada

References

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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.

Reference Type DERIVED
PMID: 31707982 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29018564 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27338778 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25139667 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25073879 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23818718 (View on PubMed)

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.

Reference Type DERIVED
PMID: 21285171 (View on PubMed)

Other Identifiers

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DE019

Identifier Type: -

Identifier Source: org_study_id

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