A Study of RoActemra/Actemra (Tocilizumab) Versus Adalimumab in Combination With Methotrexate (MTX) in Patients With Moderate to Severe Active Rheumatoid Arthritis And an Inadequate Response to Treatment With Only One Tumor Necrosis Factor (TNF)-Inhibitor

NCT01283971 | Terminated Phase 4 Results

• 2 other identifiers: MA255222010-023587-40
• Study Type: interventional
• Target: 96
• Locations: 12 countries
• Sites: 170

Brief Summary

This randomized, parallel-group study will assess the efficacy and safety of RoActemra/Actemra (tocilizumab) versus adalimumab, both in combination with methotrexate (MTX) in patients with moderate to severe active rheumatoid arthritis. Patients, already treated with MTX at stable doses, will be randomized to receive either RoActemra/Actemra 8 mg/kg intravenously (IV) every 4 weeks or adalimumab 40 mg subcutaneous (SC) every 2 weeks. All patients will receive methotrexate (10-25 mg weekly) and folate (at least 5 mg weekly). The anticipated time on study treatment is 24 weeks.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Disease Activity Score 28 Joints (DAS28) Remission at Week 24

  The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) \[28 joints\], swollen joint count (SJC) \[28 joints\], patient's global assessment of disease activity \[visual analog scale: 0=no disease activity to 100=maximum disease activity\] and the erythrocyte sedimentation rate (ESR) for a total possible score of 2 to 10. DAS28 Remission is defined as a DAS28 score \<2.6.

  Week 24

Secondary Outcomes (19)

• Percentage of Participants With American College of Rheumatology (ACR20) Response at Week 24

  Baseline, Week 24

• Percentage of Participants With ACR50 Response at Week 24

  Baseline, Week 24

• Percentage of Participants With ACR70 Response at Week 24

  Baseline, Week 24

• Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) DAS28 Responses at Week 24

  Baseline, Week 24

• Percentage of Participants With DAS28 Low Disease Activity (LDAS) at Week 24

  Week 24

Study Arms (2)

Tocilizumab + Methotrexate

EXPERIMENTAL

Tocilizumab 8 mg/kg intravenous (IV) every 4 weeks + Placebo to adalimumab subcutaneous (SC) every 2 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.

Drug: tocilizumab [RoActemra/Actemra]; Drug: placebo to adalimumab; Drug: methotrexate; Drug: folate

Adalimumab + Methotrexate

ACTIVE COMPARATOR

Adalimumab 40 mg SC every 2 weeks + Placebo to tocilizumab IV every 4 weeks for 24 weeks. All participants received methotrexate 10-25 mg and folate at least 5 mg/kg weekly.

Drug: adalimumab; Drug: placebo to tocilizumab; Drug: methotrexate; Drug: folate

Interventions

tocilizumab [RoActemra/Actemra] DRUG

Tocilizumab 8 mg/kg IV every 4 weeks for 24 weeks.

Also known as: RoActemra/Actemra

Tocilizumab + Methotrexate

adalimumab DRUG

Adalimumab 40 mg SC every 2 weeks.

Adalimumab + Methotrexate

placebo to tocilizumab DRUG

Placebo to tocilizumab IV every 4 weeks for 24 weeks.

Adalimumab + Methotrexate

placebo to adalimumab DRUG

Placebo to adalimumab SC every 2 weeks for 24 weeks.

Tocilizumab + Methotrexate

methotrexate DRUG

Methotrexate 10-25 mg weekly.

Adalimumab + Methotrexate; Tocilizumab + Methotrexate

folate DRUG

Folate at least 5 mg weekly.

Adalimumab + Methotrexate; Tocilizumab + Methotrexate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients, \>/= 18 years of age
• Rheumatoid arthritis of \>/= 6 months duration (according to American College of Rheumatology (ACR) criteria)(according to ACR criteria)
• Inadequate response due to inefficacy of treatment (for at least 3 months) with only one approved Tumor Necrosis Factor (TNF)-agent other than adalimumab Depending on the TNF-inhibitor, last dose of TNF-inhibitor should have been 1 to 8 weeks before randomization to the study
• On methotrexate treatment for \>/=12 weeks immediately prior to baseline, with stable dose (10-25 mg/week) for the last 8 weeks
• Disease Activity Score (DAS28) \>3.2 at baseline
• Oral corticosteroids (\</=10 mg/day prednisone or equivalent) and non-steroidal anti-inflammatory drugs (NSAIDs) are permitted if the dose has been stable for \>/=6 weeks prior to baseline.

You may not qualify if:

• Major surgery (including joint surgery) within 8 weeks prior to screening or planned surgery within 6 months following randomization
• Rheumatic autoimmune disease other than rheumatoid arthritis
• Prior history of or current inflammatory joint disease other than rheumatoid arthritis
• Functional class IV (ACR criteria)
• History of severe allergic reaction to human, humanized or murine monoclonal antibodies
• Known active current or history of recurrent infection (including tuberculosis)
• Primary or secondary immunodeficiency (history of or currently active)
• Body weight \>150 kg
• Previous treatment with any cell-depleting therapies
• Previous treatment with tocilizumab
• Intra-articular or parenteral corticosteroids within 6 weeks prior to baseline.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (170)

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Huntsville, Alabama, 35801, United States

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Phoenix, Arizona, 85027, United States

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Tucson, Arizona, 85712, United States

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Covina, California, 91723, United States

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Escondido, California, 92025, United States

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Huntington Beach, California, 92646, United States

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La Mesa, California, 91942, United States

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Lakewood, California, 90712, United States

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Long Beach, California, 90806, United States

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Los Angeles, California, 90048, United States

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Sacramento, California, 95816-5119, United States

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San Diego, California, 92108, United States

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Westlake Village, California, 91361, United States

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Whittier, California, 90603, United States

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Whittier, California, 90606, United States

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Bridgeport, Connecticut, 06606, United States

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Hamden, Connecticut, 06518, United States

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Norwich, Connecticut, 06360, United States

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Newark, Delaware, 19713, United States

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Aventura, Florida, 33180, United States

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Fort Lauderdale, Florida, 33334, United States

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Jupiter, Florida, 33458, United States

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Melbourne, Florida, 32901, United States

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Naples, Florida, 34102, United States

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Ocala, Florida, 34474, United States

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Orlando, Florida, 32806, United States

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Ormond Beach, Florida, 32174, United States

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Palm Habor, Florida, 34684, United States

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Palm Harbor, Florida, 34684, United States

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Sarasota, Florida, 34239, United States

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Tamarac, Florida, 33321, United States

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Tampa, Florida, 33609, United States

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Atlanta, Georgia, 30342, United States

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Valdosta, Georgia, 31602, United States

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Idaho Falls, Idaho, 83404, United States

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Chicago, Illinois, 60611, United States

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Maywood, Illinois, 60153, United States

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Moline, Illinois, 61265, United States

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Springfield, Illinois, 62704, United States

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Fort Wayne, Indiana, 46804, United States

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South Bend, Indiana, 46601, United States

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Lexington, Kentucky, 40515, United States

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Baton Rouge, Louisiana, 70808, United States

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Monroe, Louisiana, 71203, United States

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Annapolis, Maryland, 21401, United States

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Cumberland, Maryland, 21502, United States

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Frederick, Maryland, 21702, United States

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Hagerstown, Maryland, 21740, United States

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Fall River, Massachusetts, 02720, United States

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Worcester, Massachusetts, 01610, United States

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Battle Creek, Michigan, 49015, United States

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Lansing, Michigan, 48910, United States

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Petoskey, Michigan, 49770, United States

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Saint Claire Shores, Michigan, 48081, United States

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Biloxi, Mississippi, 39531, United States

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Flowood, Mississippi, 39232, United States

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Tupelo, Mississippi, 38802, United States

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Springfield, Missouri, 65807, United States

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St Louis, Missouri, 63117, United States

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Reno, Nevada, 89502, United States

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Clifton, New Jersey, 07012, United States

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Manalapan, New Jersey, 07726, United States

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New Brunswick, New Jersey, 08903, United States

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Brooklyn, New York, 11201, United States

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New York, New York, 10016, United States

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New York, New York, 10029-6574, United States

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Syracuse, New York, 13210, United States

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Charlotte, North Carolina, 28204, United States

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Charlotte, North Carolina, 28210, United States

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Greensboro, North Carolina, 27408, United States

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Greenville, North Carolina, 27834, United States

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Raleigh, North Carolina, 27617, United States

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Washington, North Carolina, 27889, United States

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Cleveland, Ohio, 44195, United States

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Middleburg Heights, Ohio, 44130, United States

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Toledo, Ohio, 43606, United States

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Oklahoma City, Oklahoma, 73109, United States

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Lake Oswego, Oregon, 97035, United States

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Duncansville, Pennsylvania, 16635, United States

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Philadelphia, Pennsylvania, 19152, United States

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Pittsburgh, Pennsylvania, 15237, United States

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Pittsburgh, Pennsylvania, 15261, United States

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Willow Grove, Pennsylvania, 19090, United States

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Wynnewood, Pennsylvania, 19096, United States

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Wyomissing, Pennsylvania, 19610, United States

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Charleston, South Carolina, 29406, United States

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Myrtle Beach, South Carolina, 29572, United States

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Jackson, Tennessee, 38305, United States

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Memphis, Tennessee, 38104, United States

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Memphis, Tennessee, 38119, United States

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Austin, Texas, 78731, United States

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Carrollton, Texas, 75007, United States

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Corpus Christi, Texas, 78404, United States

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Houston, Texas, 77004, United States

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Houston, Texas, 77034, United States

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Houston, Texas, 77070, United States

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Houston, Texas, 77074, United States

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Mesquite, Texas, 75150, United States

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San Antonio, Texas, 78217, United States

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San Antonio, Texas, 78258, United States

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Sugar Land, Texas, 77479, United States

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Arlington, Virginia, 22205, United States

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Kennewick, Washington, 99336, United States

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Spokane, Washington, 99204, United States

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Tacoma, Washington, 98405, United States

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Clarksburg, West Virginia, 26301, United States

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Franklin, Wisconsin, 53132, United States

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Aalborg, 9000, Denmark

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Elsinore, 3000, Denmark

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Silkeborg, 8600, Denmark

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Helsinki, 00290, Finland

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Hyvinkää, 05800, Finland

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Jyväskylä, 40100, Finland

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Grenoble, 38042, France

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Lille, 59037, France

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Limoges, 87042, France

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Metz, 57077, France

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Montpellier, 34295, France

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Mulhouse, 68070, France

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Nantes, 44035, France

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Orléans, 45000, France

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Paris, 75651, France

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Toulouse, 31059, France

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Berlin, 14059, Germany

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Düsseldorf, 40217, Germany

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Erfurt, 99096, Germany

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Erlangen, 91056, Germany

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Frankfurt am Main, 60590, Germany

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Gommern, 39245, Germany

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Hamburg, 22081, Germany

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Hanover, 30625, Germany

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Heidelberg, 69120, Germany

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Herne, 44652, Germany

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Hildesheim, 31134, Germany

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München, 81541, Germany

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Osnabrück, 49074, Germany

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Regensburg, 93053, Germany

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Rostock, 18059, Germany

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Tübingen, 72076, Germany

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Athens, 11527, Greece

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Heraklion, 71110, Greece

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Thessaloniki, 546 42, Greece

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Thessaloniki, 54642, Greece

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Florence, 50139, Italy

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Milan, 20162, Italy

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Pavia, 27100, Italy

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Pisa, 56100, Italy

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Roma, 00161, Italy

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Nijmegen, 6522 JV, Netherlands

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Caguas, 00725, Puerto Rico

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Kemerovo, 650099, Russia

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Moscow, 115522, Russia

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Moscow, 119049, Russia

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Ufa, 450005, Russia

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Ulyanovsk, 432063, Russia

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Sabadell, Barcelona, 08208, Spain

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A Coruña, La Coruña, 15006, Spain

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Santiago de Compostela, La Coruña, 15706, Spain

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Madrid, Madrid, 28007, Spain

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Madrid, Madrid, 28046, Spain

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Málaga, Malaga, 29010, Spain

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Oviedo, Principality of Asturias, 33006, Spain

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Valenica, Valencia, 46009, Spain

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Barakaldo, Vizcaya, 48903, Spain

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Gothenburg, 413 45, Sweden

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Huddinge, SE-141 86, Sweden

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Lund, 221 85, Sweden

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Malmo, 205 02, Sweden

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Umeå, 90185, Sweden

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Västerås, 72189, Sweden

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MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tocilizumab; Adalimumab; Methotrexate; Folic Acid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Data interpretation was limited by the very small sample size (enrollment 1/7 of planned sample size; not powered for formal statistical analysis) and the open-label observation (study un-blinded following protocol amendment to terminate enrollment).

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffman-LaRoche

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2011
• First Posted: January 26, 2011
• Study Start: May 1, 2011
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: February 10, 2014
• Results First Posted: February 10, 2014

Record last verified: 2014-01

Locations

US (107); FI (3); FR (10); SE (6); NL (1); DK (3); GR (4); DE (16); PR (1); IT (5); RU (5); ES (9)