A Study to Assess the Effect of Tocilizumab + Methotrexate on Prevention of Structural Joint Damage in Patients With Moderate to Severe Active Rheumatoid Arthritis (RA)

NCT ID: NCT00106535

Last Updated: 2014-02-06

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1196 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-01-31

Study Completion Date

2012-07-31

Brief Summary

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This 3 arm study will compare the safety and efficacy, with respect to a reduction in signs and symptoms and prevention of joint damage, of tocilizumab versus placebo, both in combination with methotrexate (MTX) in patients with moderate to severe active rheumatoid arthritis. Patients will be randomized to receive tocilizumab 4 mg/kg IV, tocilizumab 8 mg/kg IV or placebo IV, every 4 weeks. All patients will also receive methotrexate, 10-25 mg/week. The anticipated time on study treatment is 1-2 years and the target sample size is 500+ individuals. After completion of the 2 year study participants could participate in the optional 3 year open label extension phase (year 3 to 5).

Detailed Description

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Conditions

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Rheumatoid Arthritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Tocilizumab 4 mg/kg + Methotrexate

Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly for 52 weeks. From Week 16 participants with \< 20% improvement in swollen and tender joints counts were eligible for escape therapy with tocilizumab. After Week 52 participants were able to switch to open label treatment with tocilizumab 8 mg/kg every 4 weeks for 12 months in year 2 (except patients who had a \>70% improvement in both swollen and tender joint counts who remained on blinded treatment). Participants who completed year 2 of the study were eligible to enter an optional open-label long-term extension period (Year 3 to 5) and received Tocilizumab 8 mg/kg every 4 weeks.

Group Type EXPERIMENTAL

tocilizumab [RoActemra/Actemra]

Intervention Type DRUG

4 mg/kg or 8 mg/kg IV/month every 4 weeks.

Methotrexate

Intervention Type DRUG

10-25 mg/week

Tocilizumab 8 mg/kg + Methotrexate

Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly for 52 weeks. From Week 16 participants with \< 20% improvement in swollen and tender joints counts were eligible for escape therapy with tocilizumab. After Week 52 participants were able to switch to open label treatment with tocilizumab 8 mg/kg every 4 weeks for 12 months in year 2 (except patients who had a \>70% improvement in both swollen and tender joint counts who remained on blinded treatment). Participants who completed year 2 of the study were eligible to enter an optional open-label long-term extension period (Year 3 to 5) and received Tocilizumab 8 mg/kg every 4 weeks.

Group Type EXPERIMENTAL

tocilizumab [RoActemra/Actemra]

Intervention Type DRUG

4 mg/kg or 8 mg/kg IV/month every 4 weeks.

Methotrexate

Intervention Type DRUG

10-25 mg/week

Placebo + Methotrexate

Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly for 52 weeks. From Week 16 participants with \< 20% improvement in swollen and tender joints counts were eligible for escape therapy with tocilizumab. After Week 52 participants were able to switch to open label treatment with tocilizumab 8 mg/kg every 4 weeks for 12 months in year 2 (except patients who had a \>70% improvement in both swollen and tender joint counts who remained on blinded treatment). Participants who completed year 2 of the study were eligible to enter an optional open-label long-term extension period (Year 3 to 5) and received Tocilizumab 8 mg/kg every 4 weeks.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

IV/month

Methotrexate

Intervention Type DRUG

10-25 mg/week

Interventions

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tocilizumab [RoActemra/Actemra]

4 mg/kg or 8 mg/kg IV/month every 4 weeks.

Intervention Type DRUG

Placebo

IV/month

Intervention Type DRUG

Methotrexate

10-25 mg/week

Intervention Type DRUG

Other Intervention Names

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RoActemra Actemra

Eligibility Criteria

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Inclusion Criteria

* adult patients at least 18 years of age with moderate to severe active RA for at least 6 months;
* inadequate response to a stable dose of MTX;
* patients of reproductive potential must be using reliable methods of contraception.

Exclusion Criteria

* major surgery (including joint surgery) within 8 weeks before entering study, or planned surgery within 6 months after entering study;
* prior treatment failure with an anti-tumor necrosis factor agent;
* women who are pregnant or breast-feeding.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Birmingham, Alabama, United States

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Huntsville, Alabama, United States

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Scottsdale, Arizona, United States

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Tucson, Arizona, United States

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Anaheim, California, United States

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Long Beach, California, United States

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Los Angeles, California, United States

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San Diego, California, United States

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San Francisco, California, United States

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Santa Maria, California, United States

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Torrance, California, United States

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Boulder, Colorado, United States

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Colorado Springs, Colorado, United States

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Denver, Colorado, United States

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Aventura, Florida, United States

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Fort Lauderdale, Florida, United States

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Tampa, Florida, United States

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West Palm Beach, Florida, United States

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Boise, Idaho, United States

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Coeur d'Alene, Idaho, United States

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Idaho Falls, Idaho, United States

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Meridan, Idaho, United States

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Chicago, Illinois, United States

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Rockford, Illinois, United States

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Indianapolis, Indiana, United States

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Lexington, Kentucky, United States

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Frederick, Maryland, United States

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Hagerstown, Maryland, United States

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Wheaton, Maryland, United States

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St Louis, Missouri, United States

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St Louis, Missouri, United States

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Billings, Montana, United States

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Missoula, Montana, United States

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Reno, Nevada, United States

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Dover, New Hampshire, United States

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Medford, New Jersey, United States

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Voorhees Township, New Jersey, United States

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Albany, New York, United States

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Brooklyn, New York, United States

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Lake Success, New York, United States

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New York, New York, United States

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Stony Brook, New York, United States

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Asheville, North Carolina, United States

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Charlotte, North Carolina, United States

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Raleigh, North Carolina, United States

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Wilmington, North Carolina, United States

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Canton, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Tulsa, Oklahoma, United States

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Eugene, Oregon, United States

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Bethlehem, Pennsylvania, United States

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Duncansville, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Wyomissing, Pennsylvania, United States

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Columbia, South Carolina, United States

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Nashville, Tennessee, United States

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Dallas, Texas, United States

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San Antonio, Texas, United States

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Olympia, Washington, United States

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Seattle, Washington, United States

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Glendale, Wisconsin, United States

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Adelaide, , Australia

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Malvern, , Australia

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Melbourne, , Australia

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New Lambton, , Australia

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Shenton Park, , Australia

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St Leonards, , Australia

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Porto Alegre, , Brazil

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Rio de Janeiro, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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Beijing, , China

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Beijing, , China

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Nanjing, , China

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Shanghai, , China

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Shanghai, , China

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Hellerup, , Denmark

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Odense, , Denmark

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Heinola, , Finland

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Helsinki, , Finland

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Oulu, , Finland

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Vantaa, , Finland

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Amiens, , France

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Bobigny, , France

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Bois-Guillaume, , France

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Bordeaux, , France

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Le Kremlin-Bicêtre, , France

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Lille, , France

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Nice, , France

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Orléans, , France

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Paris, , France

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Paris, , France

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Strasbourg, , France

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Toulouse, , France

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Vandœuvre-lès-Nancy, , France

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Athens, , Greece

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Athens, , Greece

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Athens, , Greece

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Heraklion, , Greece

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Brescia, , Italy

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Coppito, , Italy

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Florence, , Italy

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Genova, , Italy

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Milan, , Italy

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Milan, , Italy

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Napoli, , Italy

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Padua, , Italy

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Pavia, , Italy

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Pisa, , Italy

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Reggio Emilia, , Italy

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Roma, , Italy

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Torino, , Italy

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Udine, , Italy

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Valeggio sul Mincio, , Italy

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Varese, , Italy

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Verona, , Italy

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Chihuahua City, , Mexico

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Mexico City, , Mexico

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Mexico City, , Mexico

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Mexico City, , Mexico

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Mexico City, , Mexico

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Monterrey, , Mexico

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Obregón, , Mexico

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Haugesund, , Norway

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Lillehammer, , Norway

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Tromsø, , Norway

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Bydgoszcz, , Poland

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Działdowo, , Poland

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Elblag, , Poland

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Kalisz, , Poland

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Krakow, , Poland

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Krakow, , Poland

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Poznan, , Poland

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Szczecin, , Poland

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Ustroń, , Poland

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Warsaw, , Poland

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Warsaw, , Poland

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Ponce, , Puerto Rico

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San Juan, , Puerto Rico

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Cape Town, , South Africa

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Cape Town, , South Africa

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Cape Town, , South Africa

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Diepkloof, , South Africa

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Barcelona, , Spain

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Cadiz, , Spain

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Mérida, , Spain

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Sabadell, , Spain

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Santander, , Spain

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Seville, , Spain

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Lausanne, , Switzerland

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Sankt Gallen, , Switzerland

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Countries

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United States Australia Brazil China Denmark Finland France Greece Italy Mexico Norway Poland Puerto Rico South Africa Spain Switzerland

References

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Khawaja MN, Bergman MJ, Yourish J, Pei J, Reiss W, Keystone E. Routine Assessment of Patient Index Data 3 and the American College of Rheumatology/European League Against Rheumatism Provisional Remission Definitions as Predictors of Radiographic Outcome in a Rheumatoid Arthritis Clinical Trial With Tocilizumab. Arthritis Care Res (Hoboken). 2017 May;69(5):609-615. doi: 10.1002/acr.23008. Epub 2017 Apr 7.

Reference Type DERIVED
PMID: 27564431 (View on PubMed)

Kremer JM, Blanco R, Halland AM, Brzosko M, Burgos-Vargas R, Mela CM, Rowell L, Fleischmann RM. Clinical efficacy and safety maintained up to 5 years in patients with rheumatoid arthritis treated with tocilizumab in a randomised trial. Clin Exp Rheumatol. 2016 Jul-Aug;34(4):625-33. Epub 2016 Apr 15.

Reference Type DERIVED
PMID: 27087059 (View on PubMed)

Bay-Jensen AC, Platt A, Siebuhr AS, Christiansen C, Byrjalsen I, Karsdal MA. Early changes in blood-based joint tissue destruction biomarkers are predictive of response to tocilizumab in the LITHE study. Arthritis Res Ther. 2016 Jan 20;18:13. doi: 10.1186/s13075-015-0913-x.

Reference Type DERIVED
PMID: 26787505 (View on PubMed)

Keystone EC, Anisfeld A, Ogale S, Devenport JN, Curtis JR. Continued benefit of tocilizumab plus disease-modifying antirheumatic drug therapy in patients with rheumatoid arthritis and inadequate clinical responses by week 8 of treatment. J Rheumatol. 2014 Feb;41(2):216-26. doi: 10.3899/jrheum.130489. Epub 2014 Jan 15.

Reference Type DERIVED
PMID: 24429164 (View on PubMed)

Siebuhr AS, Bay-Jensen AC, Leeming DJ, Plat A, Byrjalsen I, Christiansen C, van de Heijde D, Karsdal MA. Serological identification of fast progressors of structural damage with rheumatoid arthritis. Arthritis Res Ther. 2013 Aug 14;15(4):R86. doi: 10.1186/ar4266.

Reference Type DERIVED
PMID: 23945134 (View on PubMed)

Fleischmann RM, Halland AM, Brzosko M, Burgos-Vargas R, Mela C, Vernon E, Kremer JM. Tocilizumab inhibits structural joint damage and improves physical function in patients with rheumatoid arthritis and inadequate responses to methotrexate: LITHE study 2-year results. J Rheumatol. 2013 Feb;40(2):113-26. doi: 10.3899/jrheum.120447. Epub 2013 Jan 15.

Reference Type DERIVED
PMID: 23322466 (View on PubMed)

Wang J, Bansal AT, Martin M, Germer S, Benayed R, Essioux L, Lee JS, Begovich A, Hemmings A, Kenwright A, Taylor KE, Upmanyu R, Cutler P, Harari O, Marchini J, Criswell LA, Platt A. Genome-wide association analysis implicates the involvement of eight loci with response to tocilizumab for the treatment of rheumatoid arthritis. Pharmacogenomics J. 2013 Jun;13(3):235-41. doi: 10.1038/tpj.2012.8. Epub 2012 Apr 10.

Reference Type DERIVED
PMID: 22491018 (View on PubMed)

Kremer JM, Blanco R, Brzosko M, Burgos-Vargas R, Halland AM, Vernon E, Ambs P, Fleischmann R. Tocilizumab inhibits structural joint damage in rheumatoid arthritis patients with inadequate responses to methotrexate: results from the double-blind treatment phase of a randomized placebo-controlled trial of tocilizumab safety and prevention of structural joint damage at one year. Arthritis Rheum. 2011 Mar;63(3):609-21. doi: 10.1002/art.30158.

Reference Type DERIVED
PMID: 21360490 (View on PubMed)

Other Identifiers

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WA17823

Identifier Type: -

Identifier Source: org_study_id

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