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Efficacy and Safety of Adalimumab and Methotrexate (MTX) Versus MTX Monotherapy in Subjects With Early Rheumatoid Arthritis (PREMIER)

7. Juni 2013 aktualisiert von: AbbVie (prior sponsor, Abbott)

A Prospective Multi-Centre Randomised, Double-Blind, Active Comparator-Controlled, Parallel-Groups Study Comparing the Fully Human Monoclonal Anti-TNFα Antibody Adalimumab Given Every Second Week With Methotrexate Given Weekly and the Combination of Adalimumab and Methotrexate Administered Over 2 Years in Patients With Early Rheumatoid Arthritis (PREMIER).

The purpose of the study is to assess the safety and efficacy of adalimumab in combination with methotrexate in patients with recent onset rheumatoid arthritis (RA), and to assess the long-term safety and maintenance of efficacy after treatment with adalimumab for up to 10 years.

Studienübersicht

Status

Abgeschlossen

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

This study had an initial 2-year double-blind treatment period followed by an 8-year open-label extension period, for a total of up to 10 years study duration. The study was designed to assess the potential of adalimumab + methotrexate to improve signs and symptoms of disease and to inhibit radiographic progression in patients with recent onset (disease duration less than 3 years) rheumatoid arthritis not previously treated with methotrexate. Adalimumab is a human anti-tumor necrosis factor (TNF) monoclonal antibody.

Studientyp

Interventionell

Einschreibung (Tatsächlich)

799

Phase

  • Phase 3

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienorte

  • Australien
      • Brisbane, Australien, 4102
        • Site Reference ID/Investigator# 310
      • Camperdown, Australien, 2050
        • Site Reference ID/Investigator# 755
      • Clayton, Australien, 3168
        • Site Reference ID/Investigator# 337
      • Darlinghurst, Sydney, Australien, 2010
        • Site Reference ID/Investigator# 331
      • Kogarah, Australien, 2217
        • Site Reference ID/Investigator# 745
      • Maroochydore, Australien, 4558
        • Site Reference ID/Investigator# 738
      • New Lambton, Australien, 2305
        • Site Reference ID/Investigator# 335
      • Shenton Park, Australien, 6008
        • Site Reference ID/Investigator# 737
      • South Hobart, Australien, 7004
        • Site Reference ID/Investigator# 307
      • West Heidelberg, Australien, 3081
        • Site Reference ID/Investigator# 427
      • Woodville, Australien, 5011
        • Site Reference ID/Investigator# 739
  • Belgien
      • Brussels, Belgien, 1070
        • Site Reference ID/Investigator# 753
      • Brussels, Belgien, 1090
        • Site Reference ID/Investigator# 308
      • Brussels, Belgien, 1200
        • Site Reference ID/Investigator# 752
      • Diepenbeek, Belgien, 3590
        • Site Reference ID/Investigator# 748
      • Ghent, Belgien, 9000
        • Site Reference ID/Investigator# 6136
      • Leuven, Belgien, 3000
        • Site Ref # / Investigator 98256
      • Liege, Belgien, 4000
        • Site Reference ID/Investigator# 333
  • Deutschland
      • Berlin, Deutschland, 10117
        • Site Reference ID/Investigator# 4631
      • Berlin, Deutschland, 14059
        • Site Reference ID/Investigator# 759
      • Berlin-Buch, Deutschland, 13125
        • Site Reference ID/Investigator# 3417
      • Erlangen, Deutschland, 91054
        • Site Reference ID/Investigator# 4630
      • Freiburg, Deutschland, 79106
        • Site Reference ID/Investigator# 347
      • Goerlitz, Deutschland, 02826
        • Site Reference ID/Investigator# 742
      • Leipzig, Deutschland, 04103
        • Site Reference ID/Investigator# 746
      • Munich, Deutschland, 80336
        • Site Ref # / Investigator 98125
      • Munich, Deutschland, 80336
        • Site Reference ID/Investigator# 339
      • Ratingen, Deutschland, 40882
        • Site Reference ID/Investigator# 744
      • Vogelsang-Gommern, Deutschland, 39245
        • Site Reference ID/Investigator# 338
  • Dänemark
      • Grasten, Dänemark, 6300
        • Site Ref # / Investigator 95878
  • Finnland
      • Heinola, Finnland, FI-18120
        • Site Reference ID/Investigator# 6135
      • Helsinki, Finnland, 00029
        • Site Ref # / Investigator 6134
  • Frankreich
      • Bobigny, Frankreich, 93009
        • Site Reference ID/Investigator# 428
      • Montpellier Cedex 5, Frankreich, 34295
        • Site Reference ID/Investigator# 348
      • Paris Cedex 14, Frankreich, 75679
        • Site Reference ID/Investigator# 4650
      • Pierre Benite, Frankreich, 69310
        • Site Reference ID/Investigator# 3415
      • Rennes, Frankreich, 35056
        • Site Reference ID/Investigator# 733
      • Strasbourg, Cedex 1, Frankreich, 67098
        • Site Reference ID/Investigator# 346
  • Irland
      • Cork, Irland, WDQ-23-KM9
        • Site Reference ID/Investigator# 740
      • Dublin 4, Irland
        • Site Reference ID/Investigator# 751
  • Italien
      • Genoa, Italien, 16132
        • Site Ref # / Investigator 95719
      • Naples, Italien, 80131
        • Site Reference ID/Investigator# 323
      • Udine, Italien, 33100
        • Site Reference ID/Investigator# 345
      • Verona, Italien, 37134
        • Site Reference ID/Investigator# 756
  • Kanada
      • Edmonton, Kanada, T6G 2S2
        • Site Reference ID/Investigator# 4646
      • Hamilton, Kanada, L8N 1Y2
        • Site Reference ID/Investigator# 303
      • Hamilton, Kanada, L8N 2B6
        • Site Reference ID/Investigator# 330
      • Montreal, Kanada, H2L 1S6
        • Site Reference ID/Investigator# 4634
      • Montreal, Kanada, H3Z 2Z3
        • Site Reference ID/Investigator# 311
      • Newmarket, Kanada, L3Y 3R7
        • Site Reference ID/Investigator# 309
      • Pointe-Claire, Kanada, H9J 3W3
        • Site Reference ID/Investigator# 304
      • Richmond, Kanada, V7C 5L9
        • Site Reference ID/Investigator# 4633
      • St. John's, Kanada, A1A 5E8
        • Site Reference ID/Investigator# 763
      • Toronto, Kanada, M4N 3M5
        • Site Reference ID/Investigator# 4635
      • Toronto, Kanada, M5L 3L9
        • Site Reference ID/Investigator# 490
      • Victoria, Kanada, V8V 3P9
        • Site Reference ID/Investigator# 760
      • Winnipeg, Kanada, R3N OK6
        • Site Reference ID/Investigator# 4632
    • Ontario
      • North York, Ontario, Kanada, M3H 5Y8
        • Site Ref # / Investigator 98199
  • Niederlande
      • Groningen, Niederlande, 9713 GZ
        • Site Reference ID/Investigator# 343
      • Leiden, Niederlande, 2333 ZA
        • Site Reference ID/Investigator# 6133
      • Maastricht, Niederlande, 6229 HX
        • Site Reference ID/Investigator# 317
      • Nijmegen, Niederlande, 6500 HB
        • Site Reference ID/Investigator# 315
  • Norwegen
      • Osla, Norwegen, 0027
        • Site Ref # / Investigator 95800
      • Osla, Norwegen, 0370
        • Site Ref # / Investigator 95875
  • Schweden
      • Stockholm, Schweden, 113 24
        • Site Reference ID/Investigator# 728
      • Stockholm, Schweden, 171 76
        • Site Reference ID/Investigator# 2565
      • Stockholm, Schweden, SE-141 86
        • Site Reference ID/Investigator# 4638
      • Umea, Schweden, 901 84
        • Site Ref # / Investigator 96126
      • Uppsala, Schweden, 75185
        • Site Reference ID/Investigator# 747
      • Vasteras, Schweden, S-721 89
        • Site Ref # / Investigator 96120
      • Vasteras, Schweden, S-721 89
        • Site Reference ID/Investigator# 736
  • Schweiz
      • Lausanne, Schweiz, 1011
        • Site Reference ID/Investigator# 334
  • Slowakei
      • Piestany, Slowakei, 92112
        • Site Reference ID/Investigator# 3426
  • Spanien
      • Alicante, Spanien, 03010
        • Site Ref # / Investigator 96121
      • Alicante, Spanien, 03010
        • Site Reference ID/Investigator# 735
      • Barcelona, Spanien, 08036
        • Site Reference ID/Investigator# 1525
      • Barcelona, Spanien, 08915
        • Site Reference ID/Investigator# 1528
      • Guadalajara, Spanien, 19002
        • Site Reference ID/Investigator# 750
      • Madrid, Spanien, 28040
        • Site Reference ID/Investigator# 1526
      • Madrid, Spanien, 28040
        • Site Reference ID/Investigator# 741
      • Santiago de Compostela, Spanien, 15706
        • Site Reference ID/Investigator# 390
      • Sevilla, Spanien, 41014
        • Site Reference ID/Investigator# 749
  • Tschechische Republik
      • Hradec Kralove, Tschechische Republik, 500 05
        • Site Reference ID/Investigator# 754
      • Plzen, Tschechische Republik, 305 99
        • Site Reference ID/Investigator# 332
      • Prague 2, Tschechische Republik, 128 50
        • Site Reference ID/Investigator# 734
  • Vereinigte Staaten
    • Arizona
      • Scottsdale, Arizona, Vereinigte Staaten, 85260
        • Site Reference ID/Investigator# 322
    • California
      • La Jolla, California, Vereinigte Staaten, 92037
        • Site Ref # / Investigator 95957
      • La Jolla, California, Vereinigte Staaten, 92037
        • Site Reference ID/Investigator# 429
      • Los Angeles, California, Vereinigte Staaten, 90048
        • Site Reference ID/Investigator# 2491
    • Colorado
      • Denver, Colorado, Vereinigte Staaten, 80230
        • Site Reference ID/Investigator# 2500
    • Florida
      • Aventura, Florida, Vereinigte Staaten, 33180
        • Site Reference ID/Investigator# 762
      • Sarasota, Florida, Vereinigte Staaten, 34239
        • Site Reference ID/Investigator# 328
      • Tampa, Florida, Vereinigte Staaten, 33614
        • Site Reference ID/Investigator# 327
      • Zephyrhills, Florida, Vereinigte Staaten, 33542
        • Site Reference ID/Investigator# 325
    • Illinois
      • Rockford, Illinois, Vereinigte Staaten, 61103
        • Site Reference ID/Investigator# 302
    • Maryland
      • Cumberland, Maryland, Vereinigte Staaten, 21502
        • Site Reference ID/Investigator# 319
      • Hagerstown, Maryland, Vereinigte Staaten, 21740
        • Site Ref # / Investigator 95960
      • Wheaton, Maryland, Vereinigte Staaten, 20902
        • Site Reference ID/Investigator# 326
    • Massachusetts
      • Worcester, Massachusetts, Vereinigte Staaten, 01605-0000
        • Site Reference ID/Investigator# 2533
    • Nebraska
      • Lincoln, Nebraska, Vereinigte Staaten, 68516
        • Site Reference ID/Investigator# 336
    • New Hampshire
      • Concord, New Hampshire, Vereinigte Staaten, 03301
        • Site Reference ID/Investigator# 318
    • North Carolina
      • Durham, North Carolina, Vereinigte Staaten, 27704
        • Site Reference ID/Investigator# 488
    • Ohio
      • Dayton, Ohio, Vereinigte Staaten, 45408
        • Site Reference ID/Investigator# 314
    • Oklahoma
      • Oklahoma City, Oklahoma, Vereinigte Staaten, 73103
        • Site Reference ID/Investigator# 761
    • Oregon
      • Eugene, Oregon, Vereinigte Staaten, 97401
        • Site Reference ID/Investigator# 757
      • Lake Oswego, Oregon, Vereinigte Staaten, 97035
        • Site Reference ID/Investigator# 361
    • Pennsylvania
      • Bethlehem, Pennsylvania, Vereinigte Staaten, 18015
        • Site Reference ID/Investigator# 316
      • Duncansville, Pennsylvania, Vereinigte Staaten, 16635
        • Site Reference ID/Investigator# 4649
    • Texas
      • Austin, Texas, Vereinigte Staaten, 78705
        • Site Ref # / Investigator 96122
      • Austin, Texas, Vereinigte Staaten, 78705
        • Site Reference ID/Investigator# 306
      • Austin, Texas, Vereinigte Staaten, 78705
        • Site Reference ID/Investigator# 313
      • Dallas, Texas, Vereinigte Staaten, 75231
        • Site Reference ID/Investigator# 2437
      • Houston, Texas, Vereinigte Staaten, 77074
        • Site Reference ID/Investigator# 2532
      • Houston, Texas, Vereinigte Staaten, 77074
        • Site Reference ID/Investigator# 758
    • Washington
      • Spokane, Washington, Vereinigte Staaten, 99204
        • Site Reference ID/Investigator# 321
      • Yakima, Washington, Vereinigte Staaten, 98902
        • Site Reference ID/Investigator# 305
  • Vereinigtes Königreich
      • Bangor, Vereinigtes Königreich, LL57 2PW
        • Site Ref # / Investigator 96116
      • Cambridge, Vereinigtes Königreich, CB2 0QQ
        • Site Ref # / Investigator 95877
      • Hereford, Vereinigtes Königreich, HR1 2ER
        • Site Ref # / Investigator 98258
      • Leeds, Vereinigtes Königreich, LS1 3EX
        • Site Ref # / Investigator 95795
      • London, Vereinigtes Königreich, SE1 9RT
        • Site Ref # / Investigator 95958
      • Newcastle upon Tyne, Vereinigtes Königreich, NE7 7DN
        • Site Ref # / Investigator 98255
  • Österreich
      • Vienna, Österreich, 1090
        • Site Reference ID/Investigator# 344

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre und älter (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

Inclusion Criteria:

  • Subject was age 18 or older and in good health (Investigator discretion) with a recent stable medical history.
  • Diagnosis of rheumatoid arthritis (RA) as defined by the 1987-revised American College of Rheumatology (ACR) criteria, with a disease duration less than 3 years, at least 8 swollen joints out of the 66 joints assessed, at least 10 tender joints out of the 68 joints assessed, at least 1 joint erosion or rheumatoid factor (RF) positivity, erythrocyte sedimentation rate (ESR) >= 28 mm/1h or C-reactive protein (CRP) >= 1.5 mg/dl

Exclusion Criteria:

  • Chronic arthritis diagnosed before the age of 16
  • Preceding treatment with MTX, cyclophosphamide, cyclosporin, azathioprine or more than 2 other disease-modifying anti-rheumatic drugs (DMARDs)
  • Subject previously received anti-tumor necrosis factor (TNF) therapy
  • Permanently wheelchair-bound or bedridden patients
  • Subject considered by the investigator, for any reason, to be an unsuitable candidate for the study
  • Female subject who is pregnant or breast-feeding or considering becoming pregnant

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Zufällig
  • Interventionsmodell: Parallele Zuordnung
  • Maskierung: Doppelt

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: Adalimumab
Participants received adalimumab 40 mg subcutaneous injection once every other week and placebo to methotrexate orally once a week during the 2-year double-blind treatment phase and then adalimumab 40 mg every other week for up to 8 years in the open-label extension.
Biologisch: Adalimumab
Andere Namen:
  • ABT-D2E7
  • Humira
Arzneimittel: Methotrexate placebo
Experimental: Adalimumab + methotrexate
Participants received adalimumab 40 mg subcutaneous injection once every other week and methotrexate orally once a week at a starting dose of 7.5 mg/week (could be escalated up to 20 mg/week) during the 2-year double-blind treatment phase. Participants received adalimumab 40 mg every other week for up to 8 years in the open-label extension phase.
Biologisch: Adalimumab
Andere Namen:
  • ABT-D2E7
  • Humira
Arzneimittel: Methotrexat
Experimental: Methotrexate
Participants received placebo to adalimumab subcutaneous injection once every other week and methotrexate orally once a week at a starting dose of 7.5 mg/week (could be escalated up to 20 mg/week) during the 2-year double-blind treatment phase. Participants received adalimumab 40 mg every other week for up to 8 years in the open-label extension phase.
Arzneimittel: Methotrexat
Biologisch: Adalimumab placebo

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 52
Zeitfenster: Baseline and 52 Weeks

American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:

  • ≥ 50% improvement in tender joint count;
  • ≥ 50% improvement in swollen joint count; and

  • ≥ 50% improvement in at least 3 of the 5 following parameters:

    • Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
    • Patient's global assessment of disease activity (measured on a 100 mm VAS);
    • Physician's global assessment of disease activity (measured on a 100 mm VAS);
    • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI));
    • Acute phase reactant value (C-Reactive Protein).

Participants who withdrew early were considered non-responders.
Baseline and 52 Weeks
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 52
Zeitfenster: Baseline and Week 52
The modified Total Sharp Score (mTSS) is a measure of change in joint health. Digitized images of radiographs of hands and feet obtained at screening and Week 52 were scored in a blinded manner. Joints were scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (ankylosis or complete dislocation). Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). 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.
Baseline and Week 52

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52
Zeitfenster: Baseline and Week 52
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement.
Baseline and Week 52
Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 104
Zeitfenster: Baseline and Week 104

American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:

  • ≥ 50% improvement in tender joint count;
  • ≥ 50% improvement in swollen joint count; and

  • ≥ 50% improvement in at least 3 of the 5 following parameters:

    • Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
    • Patient's global assessment of disease activity (measured on a 100 mm VAS);
    • Physician's global assessment of disease activity (measured on a 100 mm VAS);
    • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
    • Acute phase reactant value (C-Reactive Protein).

Participants withdrawing early were considered non-responders.
Baseline and Week 104
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 104
Zeitfenster: Baseline and Week 104
The modified Total Sharp Score (mTSS) is a measure of change in joint health. Digitized images of radiographs of hands and feet obtained at screening and Week 104 were scored in a blinded manner. Joints were scored for erosions on a scale of 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale of 0 (no damage) to 4 (ankylosis or complete dislocation). Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). 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.
Baseline and Week 104
Number of Participants Who Achieved Clinical Remission, Defined as a Disease Activity 28 (DAS28) Score < 2.6 at Week 52
Zeitfenster: Week 52
The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C reactive protein, and general health were included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission.
Week 52
Change From Baseline in the Physical Component of the Short Form-36 Health Status Survey (SF-36) at Week 52
Zeitfenster: Baseline and Week 52
The SF-36 determined participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 comprise the physical component of the SF-36. Scores on each item were summed and averaged (range = 0-100); increases from Baseline indicate improvement.
Baseline and Week 52
Number of Participants With Major Clinical Response After 104 Weeks of Treatment
Zeitfenster: Any 6 continuous months from Baseline to Week 104

Major clinical response was defined as an American College of Rheumatology 70% (ACR70) response for any six continuous months, over 104 weeks of treatment. A participant was a responder if the following criteria for improvement from Baseline were met:

  • ≥ 70% improvement in tender joint count;
  • ≥ 70% improvement in swollen joint count; and

  • ≥ 70% improvement in at least 3 of the 5 following parameters:

    • Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
    • Patient's global assessment of disease activity (measured on a 100 mm VAS);
    • Physician's global assessment of disease activity (measured on a 100 mm VAS);
    • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
    • Acute phase reactant value (C-Reactive Protein).

Participants withdrawing early were non-responders.
Any 6 continuous months from Baseline to Week 104
Change From Baseline in the Mental Component of the Short Form-36 Health Status Survey (SF-36) at Week 52
Zeitfenster: Baseline and Week 52
The SF-36 determined participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 5-8 comprise the mental component of the SF-36. Scores on each item were summed and averaged (range = 0-100); increases from Baseline indicate improvement.
Baseline and Week 52
Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Weeks 26 and 76
Zeitfenster: Baseline and Weeks 26 and 76

American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:

  • ≥ 50% improvement in tender joint count;
  • ≥ 50% improvement in swollen joint count; and

  • ≥ 50% improvement in at least 3 of the 5 following parameters:

    • Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
    • Patient's global assessment of disease activity (measured on a 100 mm VAS);
    • Physician's global assessment of disease activity (measured on a 100 mm VAS);
    • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
    • Acute phase reactant value (C-Reactive Protein).

Participants withdrawing early were considered non-responders.
Baseline and Weeks 26 and 76
Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria During the Double-blind Phase
Zeitfenster: Baseline and Weeks 26, 52, 76, and 104

American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:

  • ≥ 20% improvement in tender joint count;
  • ≥ 20% improvement in swollen joint count; and

  • ≥ 20% improvement in at least 3 of the 5 following parameters:

    • Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
    • Patient's global assessment of disease activity (measured on a 100 mm VAS);
    • Physician's global assessment of disease activity (measured on a 100 mm VAS);
    • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
    • Acute phase reactant value (C-Reactive Protein).

Participants withdrawing early were considered non-responders.
Baseline and Weeks 26, 52, 76, and 104
Number of Participants Meeting American College of Rheumatology 70% (ACR70) Response Criteria During the Double-blind Phase
Zeitfenster: Baseline and Weeks 26, 52, 76, and 104

American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:

  • ≥ 70% improvement in tender joint count;
  • ≥ 70% improvement in swollen joint count; and

  • ≥ 70% improvement in at least 3 of the 5 following parameters:

    • Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
    • Patient's global assessment of disease activity (measured on a 100 mm VAS);
    • Physician's global assessment of disease activity (measured on a 100 mm VAS);
    • Patient's self-assessment of physical function (Health Assessment Questionnaire Disability Index [HAQ-DI]);
    • Acute phase reactant value (C-Reactive Protein).

Participants withdrawing early were considered non-responders.
Baseline and Weeks 26, 52, 76, and 104
Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) During the Double-blind Treatment Phase
Zeitfenster: Baseline and Weeks 12, 26, 76, and 104
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement.
Baseline and Weeks 12, 26, 76, and 104
Number of Participants With Improvement in the HAQ-DI Score ≥ 0.3 During the Double-blind Treatment Phase
Zeitfenster: Baseline and Weeks 26, 52, 76, and 104
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability.
Baseline and Weeks 26, 52, 76, and 104
Change From Baseline in Health Utilities Index Mark 2 and Mark 3 (HUI 2/3) During the Double-blind Treatment Phase
Zeitfenster: Baseline and Weeks 26, 52, and 104

The HUI 2/3 is an assessment of various aspects of participants' health and ability to perform various tasks on a day-to-day basis, including reading, seeing, hearing, speaking, general outlook on life, pain/discomfort, ability to walk, use of hands, memory, ability to think/solve, and ability to perform basic activities such as eating, bathing, and dressing. The HUI 2/3 is a combined 15-item questionnaire based on a recall period of the previous 4 weeks. HUI-2 and HUI-3 scores are calculated independently. The HUI-2 score includes 6 attributes: Sensation, Mobility, Emotion, Cognition, Self-Care, and Pain. The HUI-3 score is comprised of 8 attributes: Vision, Hearing, Speech, Ambulation, Dexterity, Emotion, Cognition, and Pain.

The range of each score is from 0 (dead) to 1 (perfect health). An increase from Baseline indicates improvement.
Baseline and Weeks 26, 52, and 104
Change From Baseline in the Short Form-36 Health Status Survey (SF-36) During the Double-blind Treatment Phase
Zeitfenster: Baseline and Weeks 26 and 104
The SF-36 determined participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 comprise the physical component and items 5-8 comprise the mental component of the SF-36. Scores on each item were summed and averaged (range = 0-100); increases from Baseline indicate improvement.
Baseline and Weeks 26 and 104
Numeric American College of Rheumatology (ACR-N) During the Double-blind Treatment Phase
Zeitfenster: Baseline and Weeks 26, 52, 76, and 104
ACR-N is a composite, continuous variable which measures the percentage of improvement from Baseline in individual participants based on the 7 core set variables of the ACR. ACR-N is defined as the smallest percent change from Baseline of 3 measures: tender joint counts (TJC), swollen joint counts (SJC), and the median percent improvement in the 5 remaining measures (Patient's Assessment of Pain, Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, Health Assessment Questionnaire - Disability Index [HAQ-DI], and C-Reactive Protein). A positive ACR-N value indicates improvement; a negative ACR-N value indicates worsening; ACR-N of 0 indicates no change.
Baseline and Weeks 26, 52, 76, and 104
Change From Baseline in Disease Activity Score (DAS28) During the Double-blind Treatment Phase
Zeitfenster: Baseline and Weeks 26, 52, 76, and 104

The DAS28 is a composite score of rheumatoid arthritis disease activity derived from the following variables:

  • 28 tender joint counts,
  • 28 swollen joint counts,
  • C-reactive protein, and
  • Patient's global assessment of disease activity.

Scores on the DAS28 range from 0 to 10. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
Baseline and Weeks 26, 52, 76, and 104
Change From Baseline in Joint Erosion Score During the Double-blind Treatment Period
Zeitfenster: Baseline and Weeks 52 and 104
Digitized images of radiographs of hands and feet obtained at screening and during the study were scored in a blinded manner. Joints on each hand/wrist (17 joints) and each forefoot (6 joints) were scored for erosions on a scale of 0 = no erosions; 1 = 1 discrete erosion or ≤20% joint involvement; 2 = 2 separate quadrants with erosion or 21-40% joint involvement; 3 = 3 separate quadrants with erosion or 41-60% joint involvement; 4 = all 4 quadrants with erosion or 61-80% joint involvement; and 5 = extensive destruction with >80% joint involvement. Scores were summed to calculate the total erosion score, which ranges from 0 (no erosion)to 230 (worst). A large increase in erosion score is indicative of worsening, whereas a small change or no change is indicative of inhibition of joint erosion.
Baseline and Weeks 52 and 104
Change From Baseline in Joint Space Narrowing Score During the Double-blind Treatment Period
Zeitfenster: Baseline and Weeks 52 and 104
Digitized images of radiographs of hands and feet obtained at screening and during the study were scored in a blinded manner. Joint space narrowing (JSN) scores were recorded for each hand/wrist (16 joints) and each forefoot (5 joints) on a 5-point scale (0 = no narrowing; 1 = up to 25% narrowing; 2 = 26-65% narrowing; 3 = 66-99% narrowing; and 4 = complete narrowing). Scores were summed to calculate the total score ranging from 0 (no narrowing) to 168 (maximum narrowing). A large increase in joint narrowing score is indicative of worsening, whereas a small change or no change is indicative of inhibition of JSN.
Baseline and Weeks 52 and 104
Number of Participants With No Worsening in Modified Total Sharp Score or Components During the Double-blind Treatment Phase
Zeitfenster: Baseline and Weeks 52 and 104

The number of participants with no worsening in the modified Total Sharp Score (mTSS) and in erosion and joint space narrowing (JSN) scores, where no worsening is defined as a change from Baseline of ≤ 0 in mTSS, erosion score and JSN score, at Weeks 52 and 104.

Digitized images of radiographs of hands and feet obtained at screening and during the study were scored in a blinded manner. Joints were scored for erosions on a scale of 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale of 0 (no damage) to 4 (ankylosis or complete dislocation). Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). 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.
Baseline and Weeks 52 and 104
Number of Participants With No Erosions at Baseline and No New Erosions at Weeks 52 and 104
Zeitfenster: Baseline and Weeks 52 and 104

The number of participants with no erosions at Baseline and no erosions at Weeks 52 and 104, where no erosions and no new erosions are defined as an erosion score = 0.

Digitized images of radiographs of hands and feet obtained at screening and during the study were scored in a blinded manner. Joints on each hand/wrist (17 joints) and each forefoot (6 joints) were scored for erosions on a scale of 0 = no erosions; 1 = 1 discrete erosion or ≤20% joint involvement; 2 = 2 separate quadrants with erosion or 21-40% joint involvement; 3 = 3 separate quadrants with erosion or 41-60% joint involvement; 4 = all 4 quadrants with erosion or 61-80% joint involvement; and 5 = extensive destruction with >80% joint involvement. Scores were summed to calculate the total erosion score, which ranges from 0 (no erosion) to 230 (worst).
Baseline and Weeks 52 and 104
Number of Participants With Non-Involved Joints at Baseline and No Newly Involved Joints at Weeks 52 and 104
Zeitfenster: Baseline and Weeks 52 and 104

Number of participants with non-involved joints at Baseline and no newly involved joints at Weeks 52 and 104, where involved joints or no newly involved joints are defined as modified Total Sharp Score (mTSS) = 0.

Digitized images of radiographs of hands and feet obtained at screening and during the study were scored in a blinded manner. Joints were scored for erosions on a scale of 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale of 0 (no damage) to 4 (ankylosis or complete dislocation). Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]).
Baseline and Weeks 52 and 104
Number of Participants Meeting ACR20 Response Criteria Over 10 Years by Adalimumab Exposure
Zeitfenster: Baseline and after 1, 2, 5, and 10 years of adalimumab exposure. Baseline was the last value prior to the first dose of adalimumab.

American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:

  • ≥ 20% improvement in tender joint count;
  • ≥ 20% improvement in swollen joint count; and

  • ≥ 20% improvement in at least 3 of the 5 following parameters:

    • Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
    • Patient's global assessment of disease activity (measured on a 100 mm VAS);
    • Physician's global assessment of disease activity (measured on a 100 mm VAS);
    • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
    • Acute phase reactant value (C-Reactive Protein).

Baseline is the last value prior to the first dose of adalimumab. For participants randomized to the methotrexate (MTX) arm in the double-blind (DB) phase, Baseline was the last visit prior to the first adalimumab dose at Week 106 of the open-label (OL) phase.
Baseline and after 1, 2, 5, and 10 years of adalimumab exposure. Baseline was the last value prior to the first dose of adalimumab.
Number of Participants Meeting ACR50 Response Criteria Over 10 Years by Adalimumab Exposure
Zeitfenster: Baseline and after 1, 2, 5, and 10 years of adalimumab exposure. Baseline was the last value prior to the first dose of adalimumab.

American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:

  • ≥ 50% improvement in tender joint count;
  • ≥ 50% improvement in swollen joint count; and

  • ≥ 50% improvement in at least 3 of the 5 following parameters:

    • Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
    • Patient's global assessment of disease activity (measured on a 100 mm VAS);
    • Physician's global assessment of disease activity (measured on a 100 mm VAS);
    • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
    • Acute phase reactant value (C-Reactive Protein).

Baseline is the last value prior to the first dose of adalimumab. For patients randomized to the methotrexate (MTX) arm in the double-blind (DB) phase, Baseline was the last visit prior to the first adalimumab dose at Week 106 of the open-label (OL) phase.
Baseline and after 1, 2, 5, and 10 years of adalimumab exposure. Baseline was the last value prior to the first dose of adalimumab.
Number of Participants Meeting ACR70 Response Criteria Over 10 Years by Adalimumab Exposure
Zeitfenster: Baseline and after 1, 2, 5, and 10 years of adalimumab exposure. Baseline was the last value prior to the first dose of adalimumab.

American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:

  • ≥ 70% improvement in tender joint count;
  • ≥ 70% improvement in swollen joint count; and

  • ≥ 70% improvement in at least 3 of the 5 following parameters:

    • Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
    • Patient's global assessment of disease activity (measured on a 100 mm VAS);
    • Physician's global assessment of disease activity (measured on a 100 mm VAS);
    • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
    • Acute phase reactant value (C-Reactive Protein).

Baseline is the last value prior to the first dose of adalimumab. For patients randomized to the methotrexate (MTX) arm in the double-blind (DB) phase, Baseline was the last visit prior to the first adalimumab dose at Week 106 of the open-label (OL) phase.
Baseline and after 1, 2, 5, and 10 years of adalimumab exposure. Baseline was the last value prior to the first dose of adalimumab.
Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) Over 10 Years by Adalimumab Exposure
Zeitfenster: Baseline and Years 1, 2, 5, and 10. Baseline was the last value prior to the first dose of adalimumab. For patients randomized to the MTX arm in the DB phase, Baseline was the last visit prior to the first adalimumab dose at Week 106.
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement.
Baseline and Years 1, 2, 5, and 10. Baseline was the last value prior to the first dose of adalimumab. For patients randomized to the MTX arm in the DB phase, Baseline was the last visit prior to the first adalimumab dose at Week 106.
Change From Baseline in DAS28 Over 10 Years by Adalimumab Exposure
Zeitfenster: Baseline and Years 1, 2, 5, and 10. Baseline was the last value prior to the first dose of adalimumab. For patients randomized to the MTX arm in the DB phase, Baseline was the last visit prior to the first adalimumab dose at Week 106.

The DAS28 is a composite score of rheumatoid arthritis disease activity derived from the following variables:

  • 28 tender joint counts,
  • 28 swollen joint counts,
  • C-reactive protein, and
  • Patient's global assessment of disease activity.

Scores on the DAS28 range from 0 to 10. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
Baseline and Years 1, 2, 5, and 10. Baseline was the last value prior to the first dose of adalimumab. For patients randomized to the MTX arm in the DB phase, Baseline was the last visit prior to the first adalimumab dose at Week 106.
Number of Participants With DAS28 < 2.6 and < 3.2 Over 10 Years by Adalimumab Exposure
Zeitfenster: After 1, 2, 5, and 10 years of adalimumab exposure

The DAS28 is a composite score of rheumatoid arthritis disease activity derived from the following variables:

  • 28 tender joint counts,
  • 28 swollen joint counts,
  • C-reactive protein, and
  • Patient's global assessment of disease activity.

Scores on the DAS28 range from 0 to 10. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
After 1, 2, 5, and 10 years of adalimumab exposure
Change From Baseline in Modified Total Sharp Score (mTSS) Over 10 Years
Zeitfenster: Baseline (prior to first study drug treatment) and Years 2 and 10
The modified TSS (mTSS) is a measure of change in joint health. Digitized images of radiographs of hands and feet obtained at screening and during the study were scored in a blinded manner. Joints were scored for erosions on a scale of 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale of 0 (no damage) to 4 (ankylosis or complete dislocation). Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). 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.
Baseline (prior to first study drug treatment) and Years 2 and 10
Number of Participants With No Radiographic Progression Over 10 Years
Zeitfenster: Baseline (prior to first study drug treatment) and Years 2 and 10.
The modified Total Sharp Score (mTSS) is a measure of change in joint health. Digitized images of radiographs of hands and feet obtained at screening and during the study were scored in a blinded manner. Joints were scored for erosions on a scale of 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale of 0 (no damage) to 4 (ankylosis or complete dislocation). Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). 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. The number of participants with change from Baseline ≤ 0.5 and ≤ 0 is reported as a measure of no disease progression.
Baseline (prior to first study drug treatment) and Years 2 and 10.
Composite Score of ACR50 Plus No Change in Modified Total Sharp Score
Zeitfenster: Year 10
Year 10
Number of Participants With a Major Clinical Response Over 10 Years by Adalimumab Exposure
Zeitfenster: From the first dose of adalimumab (at Week 1 or Week 106 for patients initially randomized to methotrexate in the DB phase) to Year 10

A major clinical response was defined as maintenance of an ACR70 response for at least a 6-month continuous period at any time during the study following the first dose of adalimumab. A participant was a responder if the following criteria for improvement from Baseline were met:

  • ≥ 70% improvement in tender joint count;
  • ≥ 70% improvement in swollen joint count; and

  • ≥ 70% improvement in at least 3 of the 5 following parameters:

    • Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
    • Patient's global assessment of disease activity (measured on a 100 mm VAS);
    • Physician's global assessment of disease activity (measured on a 100 mm VAS);
    • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
    • Acute phase reactant value (C-Reactive Protein).
From the first dose of adalimumab (at Week 1 or Week 106 for patients initially randomized to methotrexate in the DB phase) to Year 10
Number of Participants With Improvement in HAQ-DI by 0.22 and 0.5 Units Over 10 Years by Adalimumab Exposure
Zeitfenster: Baseline and Years 1, 2, 5, and 10. Baseline was the last value prior to the first dose of adalimumab. For patients randomized to the MTX arm in the DB phase, Baseline was the last visit prior to the first adalimumab dose at Week 106.
The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. A decrease in the HAQ-DI score represents an improvement in physical function; a clinically significant improvement is defined as a decrease of least 0.22 from Baseline in the HAQ-DI score. The number of participants with improvement in HAQ-DI of at least 0.22 and 0.5 units from Baseline is reported.
Baseline and Years 1, 2, 5, and 10. Baseline was the last value prior to the first dose of adalimumab. For patients randomized to the MTX arm in the DB phase, Baseline was the last visit prior to the first adalimumab dose at Week 106.

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

AbbVie (prior sponsor, Abbott)

Ermittler

  • Studienleiter: Dawn Carlson, AbbVie

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Allgemeine Veröffentlichungen

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Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn

1. Dezember 2000

Primärer Abschluss (Tatsächlich)

1. April 2004

Studienabschluss (Tatsächlich)

1. April 2012

Studienanmeldedaten

Zuerst eingereicht

13. September 2005

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

13. September 2005

Zuerst gepostet (Schätzen)

20. September 2005

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Schätzen)

12. Juli 2013

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

7. Juni 2013

Zuletzt verifiziert

1. Juni 2013

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • DE013

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