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

A Multicenter, Randomized, Double-Period, Double - Blind Study to Determine the Optimal Protocol for Treatment Initiation With Methotrexate and Adalimumab Combination Therapy in Patients With Early Rheumatoid Arthritis (OPTIMA)

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

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Biological: adalimumab; Drug: methotrexate; Biological: placebo

Detailed Description

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

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

• Study Type: Interventional
• Enrollment (Actual): 1032
• Phase: Phase 4

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1426AAL
    • Site Reference ID/Investigator# 3886
  • Buenos Aires, Argentina, C1015ABO
    • Site Reference ID/Investigator# 3888
  • Buenos Aires, Argentina, C1055AAF
    • Site Reference ID/Investigator# 6346
  • Quilmes, Argentina
    • Site Reference ID/Investigator# 3887
  • San Miguel de Tucuman, Argentina, T4000AXL
    • Site Reference ID/Investigator# 3889
• Australia
  • Campsie, Sydney, Australia, 2194
    • Site Reference ID/Investigator# 8380
  • Clayton, Australia, 3168
    • Site Reference ID/Investigator# 6954
  • Malvern East, Australia, 3145
    • Site Reference ID/Investigator# 6940
• Austria
  • Graz, Austria, 8036
    • Site Reference ID/Investigator# 3915
  • Graz, Austria, A-8020
    • Site Reference ID/Investigator# 3911
  • Vienna, Austria, 1090
    • Site Reference ID/Investigator# 3880
  • Vienna, Austria, 1100
    • Site Reference ID/Investigator# 3885
  • Vienna, Austria, 1130
    • Site Reference ID/Investigator# 3916
  • Vienna, Austria, 1160
    • Site Reference ID/Investigator# 7792
• Belgium
  • Brussels, Belgium, 1200
    • Site Reference ID/Investigator# 3914
  • Genk, Belgium, 3600
    • Site Reference ID/Investigator# 3909
  • Gilly, Belgium, 6060
    • Site Reference ID/Investigator# 3881
  • Liege, Belgium, 4000
    • Site Reference ID/Investigator# 3376
  • Mechelen, Belgium, 2800
    • Site Reference ID/Investigator# 6720
  • Sint-Niklaas, Belgium, 9100
    • Site Reference ID/Investigator# 6718
  • Yvoir, Belgium, 5530
    • Site Reference ID/Investigator# 3910
• Canada
  • Burlington, Canada, L7R 1E2
    • Site Reference ID/Investigator# 6701
  • Edmonton, Canada, T5M 0H4
    • Site Reference ID/Investigator# 6834
  • Halifax, Canada, B3H 4K4
    • Site Reference ID/Investigator# 7197
  • Hamilton, Canada, L8N 1Y2
    • Site Reference ID/Investigator# 3883
  • Hamilton, Canada, L8N 2B6
    • Site Reference ID/Investigator# 3884
  • Montreal, Canada, H2L 1S6
    • Site Reference ID/Investigator# 3907
  • Montreal, Canada, H3Z 2Z3
    • Site Reference ID/Investigator# 3903
  • Ottawa, Canada, K2G 6E2
    • Site Reference ID/Investigator# 5178
  • Richmond, Canada, V7C 5L9
    • Site Reference ID/Investigator# 3904
  • Sainte-Foy, Quebec, Canada, G1W 4R4
    • Site Reference ID/Investigator# 3912
  • Sarnia, Canada, N7T 5W6
    • Site Reference ID/Investigator# 3901
  • St. John's, Canada, A1A 5E8
    • Site Reference ID/Investigator# 3906
  • Toronto, Canada, M9B 1B1
    • Site Reference ID/Investigator# 6542
  • Victoria, Canada, V8V 3P9
    • Site Reference ID/Investigator# 3882
  • Windsor, Canada, N8X 5A6
    • Site Reference ID/Investigator# 5616
  • Winnipeg, Canada, R3A 1M3
    • Site Reference ID/Investigator# 5847
  • Winnipeg, Canada, R3A 1M4
    • Site Reference ID/Investigator# 3905
• Czech Republic
  • Brno, Czech Republic, 65691
    • Site Reference ID/Investigator# 3968
  • Hradec Kralove, Czech Republic, 500 05
    • Site Reference ID/Investigator# 3971
  • Ostrava, Czech Republic, 72200
    • Site Reference ID/Investigator# 5559
  • Prague 2, Czech Republic, 128 50
    • Site Reference ID/Investigator# 3969
  • Uherske Hradiste, Czech Republic, 686 01
    • Site Reference ID/Investigator# 5548
• France
  • Amiens, France, 80054
    • Site Reference ID/Investigator# 3982
  • Le Mans, France, 72037
    • Site Reference ID/Investigator# 3979
  • Paris Cedex 14, France, 75679
    • Site Reference ID/Investigator# 3983
  • Strasbourg, France, 67098
    • Site Reference ID/Investigator# 3918
• Germany
  • Bad Nauheim, Germany, D-61231
    • Site Reference ID/Investigator# 3926
  • Berlin-Buch, Germany, 13125
    • Site Reference ID/Investigator# 3928
  • Damp, Germany, 24351
    • Site Reference ID/Investigator# 3978
  • Duesseldorf, Germany, 40225
    • Site Reference ID/Investigator# 3924
  • Frankfurt, Germany, 60590
    • Site Reference ID/Investigator# 3965
  • Frankfurt/Main, Germany, 60596
    • Site Reference ID/Investigator# 3927
  • Freiburg, Germany, 79106
    • Site Reference ID/Investigator# 3925
  • Halle, Germany, 06120
    • Site Reference ID/Investigator# 4291
  • Hofheim, Germany, D-65719
    • Site Reference ID/Investigator# 8489
  • Munich, Germany, 80336
    • Site Reference ID/Investigator# 3923
  • Osnabrueck, Germany, D-49074
    • Site Reference ID/Investigator# 8483
  • Ratingen, Germany, 40882
    • Site Reference ID/Investigator# 8486
  • Vogelsang-Gommern, Germany, 39245
    • Site Reference ID/Investigator# 3919
  • Zerbst, Germany, 39261
    • Site Reference ID/Investigator# 6637
• Hungary
  • Budapest, Hungary, 1023
    • Site Reference ID/Investigator# 3921
  • Budapest, Hungary, 1277
    • Site Reference ID/Investigator# 3922
  • Debrecen, Hungary, 4012
    • Site Reference ID/Investigator# 3920
• Mexico
  • Aguascallentes, Mexico, 20230
    • Site Reference ID/Investigator# 3824
  • Leon, Guanajuato, Mexico, 37000
    • Site Reference ID/Investigator# 3822
  • Mexico City, Mexico, 10700
    • Site Reference ID/Investigator# 3825
  • Mexico City, Mexico, 10700
    • Site Reference ID/Investigator# 3951
  • Mexico City, Mexico, 14389
    • Site Reference ID/Investigator# 3890
  • Mexico City, Mexico, CP 1300
    • Site Reference ID/Investigator# 3823
  • Mexico City, Mexico, CP 14050
    • Site Reference ID/Investigator# 3891
• Netherlands
  • Arnem, Netherlands, 6815 AD
    • Site Reference ID/Investigator# 3947
  • Hilversum, Netherlands, 1213XZ
    • Site Reference ID/Investigator# 3948
• New Zealand
  • Auckland 6, New Zealand
    • Site Reference ID/Investigator# 8485
  • Hamilton, New Zealand
    • Site Reference ID/Investigator# 8488
  • Timaru, New Zealand
    • Site Reference ID/Investigator# 8496
  • Wellington, New Zealand
    • Site Reference ID/Investigator# 8511
• Norway
  • Alesund, Norway, N-6026
    • Site Reference ID/Investigator# 7607
  • Kristiansand S, Norway, 4615
    • Site Reference ID/Investigator# 7935
  • Levanger, Norway, 7600
    • Site Reference ID/Investigator# 7506
  • Lillehammer, Norway, N-2609
    • Site Reference ID/Investigator# 7511
  • Trondheim, Norway, N-7006
    • Site Reference ID/Investigator# 7500
• Poland
  • Bydgoszcz, Poland, 85168
    • Site Reference ID/Investigator# 3963
  • Katowice, Poland, 40635
    • Site Reference ID/Investigator# 3962
  • Lublin, Poland, 20954
    • Site Reference ID/Investigator# 5560
  • Wroclaw, Poland, 53-342
    • Site Reference ID/Investigator# 3961
• Puerto Rico
  • Caguas, Puerto Rico, 00725
    • Site Reference ID/Investigator# 3944
  • Ponce, Puerto Rico, 00716
    • Site Reference ID/Investigator# 3937
  • San Juan, Puerto Rico, 00918
    • Site Reference ID/Investigator# 3934
  • San Juan, Puerto Rico, 00936-5067
    • Site Reference ID/Investigator# 3935
• Slovakia
  • Piestany, Slovakia, 92112
    • Site Reference ID/Investigator# 3959
  • Piestany, Slovakia, 92112
    • Site Reference ID/Investigator# 3960
• South Africa
  • Berea, Durban, South Africa, 4001
    • Site Reference ID/Investigator# 7177
  • Cape Town, South Africa, 7405
    • Site Reference ID/Investigator# 7175
  • Cape Town, South Africa, 7500
    • Site Reference ID/Investigator# 7178
  • Port Elizabeth, South Africa, 6045
    • Site Reference ID/Investigator# 7176
  • Pretoria, South Africa, 0028
    • Site Reference ID/Investigator# 7172
  • Soweto, South Africa, 2013
    • Site Reference ID/Investigator# 7174
• Spain
  • A Coruna, Spain, 15006
    • Site Reference ID/Investigator# 3955
  • Bilbao, Spain, 48013
    • Site Reference ID/Investigator# 13661
  • Elche (Alicante), Spain, 03203
    • Site Reference ID/Investigator# 3930
  • Madrid, Spain, 28006
    • Site Reference ID/Investigator# 8524
  • Madrid, Spain, 28007
    • Site Reference ID/Investigator# 3956
  • Madrid, Spain, 28034
    • Site Reference ID/Investigator# 3943
  • Madrid, Spain, 28046
    • Site Reference ID/Investigator# 3931
  • Oviedo, Spain, 33006
    • Site Reference ID/Investigator# 3957
  • Santiago de Compostela, Spain, 15706
    • Site Reference ID/Investigator# 3954
  • Zaragoza, Spain, 50009
    • Site Reference ID/Investigator# 3932
• Sweden
  • Eskilstuna, Sweden, SE-631 88
    • Site Reference ID/Investigator# 4015
  • Falun, Sweden, SE-79182
    • Site Reference ID/Investigator# 3984
  • Malmoe, Sweden, 20502
    • Site Reference ID/Investigator# 4016
  • Stockholm, Sweden, 171 76
    • Site Reference ID/Investigator# 4014
  • Uppsala, Sweden, 75185
    • Site Reference ID/Investigator# 4017
• United Kingdom
  • Bath, United Kingdom, BA1 1RL
    • Site Reference ID/Investigator# 4012
  • Huddersfield, United Kingdom, HD3 3EA
    • Site Reference ID/Investigator# 8495
  • Leeds, United Kingdom, LS7 4SA
    • Site Reference ID/Investigator# 4048
  • London, United Kingdom, SE1 9RT
    • Site Reference ID/Investigator# 4013
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Site Reference ID/Investigator# 4046
  • Oxford, United Kingdom, OX3 7LD
    • Site Reference ID/Investigator# 4047
  • Southampton, United Kingdom, S016 6YD
    • Site Reference ID/Investigator# 3985
  • York, United Kingdom, YO31 8HE
    • Site Reference ID/Investigator# 7977
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Site Reference ID/Investigator# 4560
    • Birmingham, Alabama, United States, 35294-7201
      • Site Reference ID/Investigator# 4547
    • Huntsville, Alabama, United States, 35801
      • Site Reference ID/Investigator# 6222
    • Mobile, Alabama, United States, 36608
      • Site Reference ID/Investigator# 4537
    • Tuscaloosa, Alabama, United States, 35406
      • Site Reference ID/Investigator# 6758
  • California
    • Hemet, California, United States, 92543
      • Site Reference ID/Investigator# 9323
    • La Jolla, California, United States, 92037-0943
      • Site Reference ID/Investigator# 4568
    • Palm Desert, California, United States, 92260
      • Site Reference ID/Investigator# 4535
    • Santa Monica, California, United States, 90404
      • Site Reference ID/Investigator# 4571
    • Torrance, California, United States, 90505
      • Site Reference ID/Investigator# 9271
    • Victorville, California, United States, 92395
      • Site Reference ID/Investigator# 10746
  • Colorado
    • Denver, Colorado, United States, 80230
      • Site Reference ID/Investigator# 4559
  • Florida
    • Aventura, Florida, United States, 33180
      • Site Reference ID/Investigator# 6229
    • Lake Mary, Florida, United States, 32746
      • Site Reference ID/Investigator# 10603
    • Orange Park, Florida, United States, 32073
      • Site Reference ID/Investigator# 9325
    • Palm Harbor, Florida, United States, 34684
      • Site Reference ID/Investigator# 4550
    • Sarasota, Florida, United States, 34239
      • Site Reference ID/Investigator# 4570
    • Tampa, Florida, United States, 33614
      • Site Reference ID/Investigator# 4601
    • Vero Beach, Florida, United States, 32960
      • Site Reference ID/Investigator# 4552
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Site Reference ID/Investigator# 10745
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Site Reference ID/Investigator# 4548
    • Springfield, Illinois, United States, 62704
      • Site Reference ID/Investigator# 4557
  • Kansas
    • Wichita, Kansas, United States, 67203
      • Site Reference ID/Investigator# 4605
  • Maryland
    • Wheaton, Maryland, United States, 20902
      • Site Reference ID/Investigator# 10741
  • Massachusetts
    • Fall River, Massachusetts, United States, 02720
      • Site Reference ID/Investigator# 6417
  • New Hampshire
    • Dover, New Hampshire, United States, 03820
      • Site Reference ID/Investigator# 4561
  • New Jersey
    • Freehold, New Jersey, United States, 07728
      • Site Reference ID/Investigator# 11222
    • Passaic, New Jersey, United States, 07055
      • Site Reference ID/Investigator# 6228
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Site Reference ID/Investigator# 4544
  • New York
    • Bronx, New York, United States, 10461
      • Site Reference ID/Investigator# 12821
    • Orchard Park, New York, United States, 14127
      • Site Reference ID/Investigator# 4534
    • Plainview, New York, United States, 11803
      • Site Reference ID/Investigator# 9324
    • Smithtown, New York, United States, 11787
      • Site Reference ID/Investigator# 4600
  • Ohio
    • Mayfield Village, Ohio, United States, 44143
      • Site Reference ID/Investigator# 4549
  • Oregon
    • Bend, Oregon, United States, 97701
      • Site Reference ID/Investigator# 6227
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Site Reference ID/Investigator# 4546
    • West Reading, Pennsylvania, United States, 19611-1124
      • Site Reference ID/Investigator# 4564
    • Wexford, Pennsylvania, United States, 15090
      • Site Reference ID/Investigator# 4558
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Site Reference ID/Investigator# 4533
    • Greenville, South Carolina, United States, 29601
      • Site Reference ID/Investigator# 7482
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • Site Reference ID/Investigator# 10743
    • Nashville, Tennessee, United States, 37205
      • Site Reference ID/Investigator# 4562
  • Texas
    • Dallas, Texas, United States, 75231
      • Site Reference ID/Investigator# 4536
    • Houston, Texas, United States, 77074
      • Site Reference ID/Investigator# 4538
    • San Antonio, Texas, United States, 78217
      • Site Reference ID/Investigator# 6899
    • Tyler, Texas, United States, 75701
      • Site Reference ID/Investigator# 6381
  • Washington
    • Seattle, Washington, United States, 98133
      • Site Reference ID/Investigator# 10744
  • Wisconsin
    • Glendale, Wisconsin, United States, 53217
      • Site Reference ID/Investigator# 4545
    • Oak Creek, Wisconsin, United States, 53154
      • Site Reference ID/Investigator# 4572

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

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

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

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

Exclusion Criteria

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Abbott
• Investigators: Study Director: Laura Redden, MD, PhD, Abbott

Publications and helpful links

General Publications

• Burmester GR, Landewe R, Genovese MC, Friedman AW, Pfeifer ND, Varothai NA, Lacerda AP. Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis. Ann Rheum Dis. 2017 Feb;76(2):414-417. doi: 10.1136/annrheumdis-2016-209322. Epub 2016 Jun 23.
• Smolen J, Fleischmann R, Aletaha D, Li Y, Zhou Y, Sainsbury I, Galindo IL. Disease activity improvements with optimal discriminatory ability between treatment arms: applicability in early and established rheumatoid arthritis clinical trials. Arthritis Res Ther. 2019 Nov 10;21(1):231. doi: 10.1186/s13075-019-2005-9.
• Smolen JS, van Vollenhoven RF, Florentinus S, Chen S, Suboticki JL, Kavanaugh A. Predictors of disease activity and structural progression after treatment with adalimumab plus methotrexate or continued methotrexate monotherapy in patients with early rheumatoid arthritis and suboptimal response to methotrexate. Ann Rheum Dis. 2018 Nov;77(11):1566-1572. doi: 10.1136/annrheumdis-2018-213502. Epub 2018 Aug 3.
• Kavanaugh A, van Vollenhoven RF, Fleischmann R, Emery P, Sainsbury I, Florentinus S, Chen S, Guerette B, Kupper H, Smolen JS. Testing treat-to-target outcomes with initial methotrexate monotherapy compared with initial tumour necrosis factor inhibitor (adalimumab) plus methotrexate in early rheumatoid arthritis. Ann Rheum Dis. 2018 Feb;77(2):289-292. doi: 10.1136/annrheumdis-2017-211871. Epub 2017 Nov 16.
• Keystone EC, Breedveld FC, van der Heijde D, van Vollenhoven RF, Emery P, Smolen JS, Sainsbury I, Florentinus S, Kupper H, Chen K, Kavanaugh A. Achieving comprehensive disease control in patients with early and established rheumatoid arthritis treated with adalimumab plus methotrexate versus methotrexate alone. RMD Open. 2017 Sep 26;3(2):e000445. doi: 10.1136/rmdopen-2017-000445. eCollection 2017.
• Smolen JS, Emery P, Fleischmann R, van Vollenhoven RF, Pavelka K, Durez P, Guerette B, Kupper H, Redden L, Arora V, Kavanaugh A. Adjustment of therapy in rheumatoid arthritis on the basis of achievement of stable low disease activity with adalimumab plus methotrexate or methotrexate alone: the randomised controlled OPTIMA trial. Lancet. 2014 Jan 25;383(9914):321-32. doi: 10.1016/S0140-6736(13)61751-1. Epub 2013 Oct 26. Erratum In: Lancet. 2014 Jan 25;383(9914):308.

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: January 9, 2007
• First Submitted That Met QC Criteria: January 10, 2007
• First Posted (Estimate): January 11, 2007

Study Record Updates

• Last Update Posted (Estimate): April 18, 2012
• Last Update Submitted That Met QC Criteria: April 16, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Early Rheumatoid Arthritis; Tumor Necrosis Factor Optimization
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Adalimumab; Methotrexate
• Other Study ID Numbers: M06-810; 2006-004139-31 (EudraCT Number)