Study of the Optimal Protocol for Methotrexate and Adalimumab Combination Therapy in Early Rheumatoid Arthritis
NCT ID: NCT00420927
Last Updated: 2012-04-18
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE4
1032 participants
INTERVENTIONAL
2006-12-31
2010-07-31
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
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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
adalimumab
Adalimumab 40 mg/0.8 mL prefilled syringe injected subcutaneously (SC) every other week (eow)
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.
placebo
Placebo for adalimumab 0.8 mL prefilled syringe injected subcutaneously (SC) every other week (eow)
ADA+MTX/ADA+MTX (Arm2)
Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2
adalimumab
Adalimumab 40 mg/0.8 mL prefilled syringe injected subcutaneously (SC) every other week (eow)
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.
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
adalimumab
Adalimumab 40 mg/0.8 mL prefilled syringe injected subcutaneously (SC) every other week (eow)
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.
PBO+MTX/PBO+MTX (Arm 4)
Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2
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.
placebo
Placebo for adalimumab 0.8 mL prefilled syringe injected subcutaneously (SC) every other week (eow)
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.
adalimumab
Adalimumab 40 mg/0.8 mL prefilled syringe injected subcutaneously (SC) every other week (eow)
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.
placebo
Placebo for adalimumab 0.8 mL prefilled syringe injected subcutaneously (SC) every other week (eow)
Interventions
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adalimumab
Adalimumab 40 mg/0.8 mL prefilled syringe injected subcutaneously (SC) every other week (eow)
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.
placebo
Placebo for adalimumab 0.8 mL prefilled syringe injected subcutaneously (SC) every other week (eow)
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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 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.
18 Years
ALL
No
Sponsors
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Abbott
INDUSTRY
Responsible Party
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Principal Investigators
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Laura Redden, MD, PhD
Role: STUDY_DIRECTOR
Abbott
Locations
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Site Reference ID/Investigator# 4560
Birmingham, Alabama, United States
Site Reference ID/Investigator# 4547
Birmingham, Alabama, United States
Site Reference ID/Investigator# 6222
Huntsville, Alabama, United States
Site Reference ID/Investigator# 4537
Mobile, Alabama, United States
Site Reference ID/Investigator# 6758
Tuscaloosa, Alabama, United States
Site Reference ID/Investigator# 9323
Hemet, California, United States
Site Reference ID/Investigator# 4568
La Jolla, California, United States
Site Reference ID/Investigator# 4535
Palm Desert, California, United States
Site Reference ID/Investigator# 4571
Santa Monica, California, United States
Site Reference ID/Investigator# 9271
Torrance, California, United States
Site Reference ID/Investigator# 10746
Victorville, California, United States
Site Reference ID/Investigator# 4559
Denver, Colorado, United States
Site Reference ID/Investigator# 6229
Aventura, Florida, United States
Site Reference ID/Investigator# 10603
Lake Mary, Florida, United States
Site Reference ID/Investigator# 9325
Orange Park, Florida, United States
Site Reference ID/Investigator# 4550
Palm Harbor, Florida, United States
Site Reference ID/Investigator# 4570
Sarasota, Florida, United States
Site Reference ID/Investigator# 4601
Tampa, Florida, United States
Site Reference ID/Investigator# 4552
Vero Beach, Florida, United States
Site Reference ID/Investigator# 10745
Meridian, Idaho, United States
Site Reference ID/Investigator# 4548
Chicago, Illinois, United States
Site Reference ID/Investigator# 4557
Springfield, Illinois, United States
Site Reference ID/Investigator# 4605
Wichita, Kansas, United States
Site Reference ID/Investigator# 10741
Wheaton, Maryland, United States
Site Reference ID/Investigator# 6417
Fall River, Massachusetts, United States
Site Reference ID/Investigator# 4561
Dover, New Hampshire, United States
Site Reference ID/Investigator# 11222
Freehold, New Jersey, United States
Site Reference ID/Investigator# 6228
Passaic, New Jersey, United States
Site Reference ID/Investigator# 4544
Albuquerque, New Mexico, United States
Site Reference ID/Investigator# 4534
Orchard Park, New York, United States
Site Reference ID/Investigator# 9324
Plainview, New York, United States
Site Reference ID/Investigator# 4600
Smithtown, New York, United States
Site Reference ID/Investigator# 12821
The Bronx, New York, United States
Site Reference ID/Investigator# 4549
Mayfield Village, Ohio, United States
Site Reference ID/Investigator# 6227
Bend, Oregon, United States
Site Reference ID/Investigator# 4546
Duncansville, Pennsylvania, United States
Site Reference ID/Investigator# 4564
West Reading, Pennsylvania, United States
Site Reference ID/Investigator# 4558
Wexford, Pennsylvania, United States
Site Reference ID/Investigator# 4533
Charleston, South Carolina, United States
Site Reference ID/Investigator# 7482
Greenville, South Carolina, United States
Site Reference ID/Investigator# 10743
Jackson, Tennessee, United States
Site Reference ID/Investigator# 4562
Nashville, Tennessee, United States
Site Reference ID/Investigator# 4536
Dallas, Texas, United States
Site Reference ID/Investigator# 4538
Houston, Texas, United States
Site Reference ID/Investigator# 6899
San Antonio, Texas, United States
Site Reference ID/Investigator# 6381
Tyler, Texas, United States
Site Reference ID/Investigator# 10744
Seattle, Washington, United States
Site Reference ID/Investigator# 4545
Glendale, Wisconsin, United States
Site Reference ID/Investigator# 4572
Oak Creek, Wisconsin, United States
Site Reference ID/Investigator# 3886
Buenos Aires, , Argentina
Site Reference ID/Investigator# 3888
Buenos Aires, , Argentina
Site Reference ID/Investigator# 6346
Buenos Aires, , Argentina
Site Reference ID/Investigator# 3887
Quilmes, , Argentina
Site Reference ID/Investigator# 3889
San Miguel de Tucumán, , Argentina
Site Reference ID/Investigator# 8380
Campsie, Sydney, , Australia
Site Reference ID/Investigator# 6954
Clayton, , Australia
Site Reference ID/Investigator# 6940
Malvern East, , Australia
Site Reference ID/Investigator# 3915
Graz, , Austria
Site Reference ID/Investigator# 3911
Graz, , Austria
Site Reference ID/Investigator# 3880
Vienna, , Austria
Site Reference ID/Investigator# 3885
Vienna, , Austria
Site Reference ID/Investigator# 3916
Vienna, , Austria
Site Reference ID/Investigator# 7792
Vienna, , Austria
Site Reference ID/Investigator# 3914
Brussels, , Belgium
Site Reference ID/Investigator# 3909
Genk, , Belgium
Site Reference ID/Investigator# 3881
Gilly, , Belgium
Site Reference ID/Investigator# 3376
Liège, , Belgium
Site Reference ID/Investigator# 6720
Mechelen, , Belgium
Site Reference ID/Investigator# 6718
Sint-Niklaas, , Belgium
Site Reference ID/Investigator# 3910
Yvoir, , Belgium
Site Reference ID/Investigator# 6701
Burlington, , Canada
Site Reference ID/Investigator# 6834
Edmonton, , Canada
Site Reference ID/Investigator# 7197
Halifax, , Canada
Site Reference ID/Investigator# 3883
Hamilton, , Canada
Site Reference ID/Investigator# 3884
Hamilton, , Canada
Site Reference ID/Investigator# 3907
Montreal, , Canada
Site Reference ID/Investigator# 3903
Montreal, , Canada
Site Reference ID/Investigator# 5178
Ottawa, , Canada
Site Reference ID/Investigator# 3904
Richmond, , Canada
Site Reference ID/Investigator# 3912
Sainte-Foy, Quebec, , Canada
Site Reference ID/Investigator# 3901
Sarnia, , Canada
Site Reference ID/Investigator# 3906
St. John's, , Canada
Site Reference ID/Investigator# 6542
Toronto, , Canada
Site Reference ID/Investigator# 3882
Victoria, , Canada
Site Reference ID/Investigator# 5616
Windsor, , Canada
Site Reference ID/Investigator# 5847
Winnipeg, , Canada
Site Reference ID/Investigator# 3905
Winnipeg, , Canada
Site Reference ID/Investigator# 3968
Brno, , Czechia
Site Reference ID/Investigator# 3971
Hradec Králové, , Czechia
Site Reference ID/Investigator# 5559
Ostrava, , Czechia
Site Reference ID/Investigator# 3969
Prague, , Czechia
Site Reference ID/Investigator# 5548
Uherské Hradiště, , Czechia
Site Reference ID/Investigator# 3982
Amiens, , France
Site Reference ID/Investigator# 3979
Le Mans, , France
Site Reference ID/Investigator# 3983
Paris, , France
Site Reference ID/Investigator# 3918
Strasbourg, , France
Site Reference ID/Investigator# 3926
Bad Nauheim, , Germany
Site Reference ID/Investigator# 3928
Buch, , Germany
Site Reference ID/Investigator# 3978
Damp, , Germany
Site Reference ID/Investigator# 3924
Düsseldorf, , Germany
Site Reference ID/Investigator# 3965
Frankfurt, , Germany
Site Reference ID/Investigator# 3927
Frankfurt am Main, , Germany
Site Reference ID/Investigator# 3925
Freiburg im Breisgau, , Germany
Site Reference ID/Investigator# 4291
Halle, , Germany
Site Reference ID/Investigator# 8489
Hofheim, , Germany
Site Reference ID/Investigator# 3923
Munich, , Germany
Site Reference ID/Investigator# 8483
Osnabrück, , Germany
Site Reference ID/Investigator# 8486
Ratingen, , Germany
Site Reference ID/Investigator# 3919
Vogelsang-Gommern, , Germany
Site Reference ID/Investigator# 6637
Zerbst, , Germany
Site Reference ID/Investigator# 3921
Budapest, , Hungary
Site Reference ID/Investigator# 3922
Budapest, , Hungary
Site Reference ID/Investigator# 3920
Debrecen, , Hungary
Site Reference ID/Investigator# 3824
Aguascallentes, , Mexico
Site Reference ID/Investigator# 3822
León, , Mexico
Site Reference ID/Investigator# 3825
Mexico City, , Mexico
Site Reference ID/Investigator# 3951
Mexico City, , Mexico
Site Reference ID/Investigator# 3890
Mexico City, , Mexico
Site Reference ID/Investigator# 3823
Mexico City, , Mexico
Site Reference ID/Investigator# 3891
Mexico City, , Mexico
Site Reference ID/Investigator# 3947
Arnhem, , Netherlands
Site Reference ID/Investigator# 3948
Hilversum, , Netherlands
Site Reference ID/Investigator# 8485
Auckland, , New Zealand
Site Reference ID/Investigator# 8488
Hamilton, , New Zealand
Site Reference ID/Investigator# 8496
Timaru, , New Zealand
Site Reference ID/Investigator# 8511
Wellington, , New Zealand
Site Reference ID/Investigator# 7607
Ålesund, , Norway
Site Reference ID/Investigator# 7935
Kristiansand, , Norway
Site Reference ID/Investigator# 7506
Levanger, , Norway
Site Reference ID/Investigator# 7511
Lillehammer, , Norway
Site Reference ID/Investigator# 7500
Trondheim, , Norway
Site Reference ID/Investigator# 3963
Bydgoszcz, , Poland
Site Reference ID/Investigator# 3962
Katowice, , Poland
Site Reference ID/Investigator# 5560
Lublin, , Poland
Site Reference ID/Investigator# 3961
Wroclaw, , Poland
Site Reference ID/Investigator# 3944
Caguas, , Puerto Rico
Site Reference ID/Investigator# 3937
Ponce, , Puerto Rico
Site Reference ID/Investigator# 3934
San Juan, , Puerto Rico
Site Reference ID/Investigator# 3935
San Juan, , Puerto Rico
Site Reference ID/Investigator# 3959
Piešťany, , Slovakia
Site Reference ID/Investigator# 3960
Piešťany, , Slovakia
Site Reference ID/Investigator# 7177
Berea, Durban, , South Africa
Site Reference ID/Investigator# 7175
Cape Town, , South Africa
Site Reference ID/Investigator# 7178
Cape Town, , South Africa
Site Reference ID/Investigator# 7176
Port Elizabeth, , South Africa
Site Reference ID/Investigator# 7172
Pretoria, , South Africa
Site Reference ID/Investigator# 7174
Soweto, , South Africa
Site Reference ID/Investigator# 3955
A Coruña, , Spain
Site Reference ID/Investigator# 13661
Bilbao, , Spain
Site Reference ID/Investigator# 3930
Elche (Alicante), , Spain
Site Reference ID/Investigator# 8524
Madrid, , Spain
Site Reference ID/Investigator# 3956
Madrid, , Spain
Site Reference ID/Investigator# 3943
Madrid, , Spain
Site Reference ID/Investigator# 3931
Madrid, , Spain
Site Reference ID/Investigator# 3957
Oviedo, , Spain
Site Reference ID/Investigator# 3954
Santiago de Compostela, , Spain
Site Reference ID/Investigator# 3932
Zaragoza, , Spain
Site Reference ID/Investigator# 4015
Eskilstuna, , Sweden
Site Reference ID/Investigator# 3984
Falun, , Sweden
Site Reference ID/Investigator# 4016
Malmo, , Sweden
Site Reference ID/Investigator# 4014
Stockholm, , Sweden
Site Reference ID/Investigator# 4017
Uppsala, , Sweden
Site Reference ID/Investigator# 4012
Bath, , United Kingdom
Site Reference ID/Investigator# 8495
Huddersfield, , United Kingdom
Site Reference ID/Investigator# 4048
Leeds, , United Kingdom
Site Reference ID/Investigator# 4013
London, , United Kingdom
Site Reference ID/Investigator# 4046
Newcastle upon Tyne, , United Kingdom
Site Reference ID/Investigator# 4047
Oxford, , United Kingdom
Site Reference ID/Investigator# 3985
Southampton, , United Kingdom
Site Reference ID/Investigator# 7977
York, , United Kingdom
Countries
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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.
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.
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 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.
Other Identifiers
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2006-004139-31
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
M06-810
Identifier Type: -
Identifier Source: org_study_id
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