Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00106535
First received: March 25, 2005
Last updated: December 18, 2013
Last verified: December 2013
  Purpose

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).


Condition Intervention Phase
Rheumatoid Arthritis
Drug: tocilizumab [RoActemra/Actemra]
Drug: Placebo
Drug: Methotrexate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind Study of Safety and Prevention of Structural Joint Damage During Treatment With Tocilizumab Versus Placebo, in Combination With Methotrexate, in Patients With Moderate to Severe Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With American College of Rheumatology-ACR20 Response [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.

  • Change From Baseline in Modified Total Sharp-Genant Score at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    Radiographs were taken of each hand and foot at Baseline and Week 52 and evaluated at a central reading service by two independent radiologists using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). The maximum total erosion score in the hands is 100 (normalized from 98) and in the feet 42, the maximum scores for joint space narrowing in the hands is 100 (normalized from 104) and in the feet 48. The maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score.

  • Change in Physical Function as Measured by the Area Under the Curve (AUC) for the Change From Baseline in the Health Assessment Questionnaire (HAQ) Disability Index at Week 52 [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: No ]
    HAQ-DI consisted of 20 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities rated on a 4-point scale where 0=without any difficulty to 3=unable to do. The sum of scores was divided by the number of domains with a score for a total possible score of 0 (best) to 3 (worst). Functional disability was determined as a cumulative measure of HAQ-DI over 1 year by using the AUC of the change from baseline in HAQ-DI score through week 52. Decreases in AUC of change from baseline in HAQ-DI indicate a greater average improvement in physical function over time and represent a decrease in sustained impairment. For patients with missing week 52 HAQ-DI score, the AUC of the change from baseline was standardized to 52 weeks using the latest timepoint available for calculation of the AUC. The mean was adjusted for region. A negative change from baseline indicated improvement.

  • Change From Baseline in the Modified Total Sharp-Genant Score at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
    Radiographs of each hand and foot were taken at Baseline and Week 104 and evaluated at a central reading service by two independent radiologists using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). The maximum total erosion score in the hands is 100 and in the feet 42, the maximum scores for joint space narrowing in the hands is 100 and in the feet 48. The maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score.

  • Change in Physical Function as Measured by the Area Under the Curve for the Change From Baseline in the Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 104 [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    HAQ-DI consisted of 20 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities rated on a 4-point scale where 0=without any difficulty to 3=unable to do. The sum of scores was divided by the number of domains with a score for a total possible score of 0 (best) to 3 (worst). Functional disability was determined as a cumulative measure of HAQ-DI over 2 years by using the AUC of the change from baseline in HAQ-DI score through week 104. Decreases in AUC of change from baseline in HAQ-DI indicated a gr eater average improvement in physical function over time and represent a decrease in sustained impairment. For patients with missing week 104 HAQ-DI score, the AUC of the change from baseline was standardized to 104 weeks using the latest timepoint available for calculation of the AUC. A negative change from baseline indicated improvement.


Secondary Outcome Measures:
  • Percentage of Participants With ACR50 Response [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].

  • Percentage of Participants With ACR70 Response [ Time Frame: Baseline,Week 24 ] [ Designated as safety issue: No ]
    ACR70 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].

  • Swollen Joint Count (66 Joint Count): Mean Change From Baseline at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    66 joints were assessed for swelling and joints are classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66.

  • Tender Joint Count (68 Joint Count): Mean Change From Baseline at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    68 joints are assessed for tenderness and joints are classified as tender/not tender giving a total possible tender joint count score of 0 to 68.

  • Patient's Global Visual Analog Scale (VAS): Mean Change From Baseline at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    The patient's global assessment of disease activity is assessed on a 0 to 100 mm horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

  • Physician's Global VAS: Mean Change From Baseline at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    The physician's global assessment of disease activity is assessed on a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as "maximum disease activity" (maximum arthritis disease activity).

  • Patient's Pain VAS: Mean Change From Baseline at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The patient assessed their pain on a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change indicated improvement.

  • C-Reactive Protein (CRP): Mean Change From Baseline at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    The serum concentration of C-Reactive Protein (CRP) is measured in mg/dL. A reduction in the level is considered an improvement.

  • Erythrocyte Sedimentation Rate: Mean Change From Baseline at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    The Erythrocyte Sedimentation Rate (ESR) was measured in mm/hr. A reduction in the level is considered an improvement.

  • Health Assessment Questionnaire Disability Index (HAQ-DI): Mean Change From Baseline at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    HAQ-DI is a self-completed patient questionnaire specific for RA. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. Calculate HAQ-DI the patient must have a domain score for at least 6 of 8 domains. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score (in range 6-8) for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from baseline indicated improvement.

  • Percentage of Participants With American College of Rheumatology (ACR20) Response at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.

  • Percentage of Participants With ACR20 Response at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
    ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.

  • Percentage of Participants With ACR50 Response at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.

  • Percentage of Participants With ACR50 Response at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
    ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.

  • Percentage of Participants With ACR70 Response at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    ACR70 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.

  • Percentage of Participants With ACR70 Response at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
    ACR50 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.

  • Percentage of Participants With ACR70 Response Maintained for 6 Consecutive Months [ Time Frame: 104 Weeks ] [ Designated as safety issue: No ]
    ACR70 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.

  • Change From Baseline in Swollen Joint Count at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    66 joints were assessed at Baseline and Week 52 for swelling and joints are classified as swollen/not swollen for a total possible swollen joint count of 0 (best) to 66 (worst). A negative change from Baseline indicated improvement.

  • Change From Baseline in Tender Joint Count at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    68 joints were assessed at Baseline and Week 52 for tenderness and joints were classified as tender/not tender for a total possible tender joint count of 0 (best) to 68 (worst). A negative change from Baseline indicated improvement.

  • Change From Baseline in Patient's Global Assessment of Disease Activity at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    The patient's global assessment of disease activity is assessed at Baseline and Week 52 using a 0 to 100 mm horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

  • Change From Baseline in Physicians Global Assessment of Disease Activity at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    The physician's global assessment of disease activity was assessed using a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

  • Change From Baseline in the Patient's Pain VAS at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    The patient assessed their pain at Baseline and Week 52 using a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change from Baseline indicated improvement.

  • Change From Baseline in C-Reactive Protein (CRP) at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    Blood was collected for C-Reactive Protein (CRP) at Baseline and Week 52 and was analyzed at a central laboratory. The serum concentration of CRP was measured in milligrams/deciliter (mg/dL). A reduction in the level is considered an improvement.

  • Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    Blood was collected for Erythrocyte Sedimentation Rate (ESR) at Baseline and Week 52 and was analyzed at a local laboratory. ESR was measured in millimeters/hour (mm/hr). A reduction in the level is considered an improvement.

  • Change From Baseline in Swollen Joint Count at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
    66 joints were assessed at Baseline and Week 104 for swelling and joints were classified as swollen/not swollen for a total possible swollen joint count of 0 (best) to 66 (worst). A negative change from Baseline indicated improvement.

  • Change From Baseline in Tender Joint Count at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
    68 joints were assessed for tenderness and joints were classified as tender/not tender for a total possible tender joint count of 0 (best) to 68 (worst). A negative change from Baseline indicated improvement.

  • Change From Baseline in Patient's Global Assessment of Disease Activity at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
    The patient's global assessment of disease activity was assessed at Baseline and Week 104 using a 0 to 100 mm horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

  • Change From Baseline in Physicians Global Assessment of Disease Activity at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
    The physician's global assessment of disease activity was assessed at Baseline and Week 104 using a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

  • Change From Baseline in the Patient's Pain VAS at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
    The patient assessed their pain at Baseline and Week 104 using a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change from Baseline indicated improvement.

  • Change From Baseline in C-Reactive Protein (CRP) at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
    Blood was collected for C-Reactive Protein (CRP) at Baseline and Week 104 and was analyzed at a central laboratory. The serum concentration of CRP was measured in milligrams/deciliter (mg/dL). A reduction in the level is considered an improvement.

  • Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
    Blood was collected for Erythrocyte Sedimentation Rate (ESR) at Baseline and Week 104 and was analyzed at a local laboratory. ESR was measured in millimeters/hour (mm/hr). A reduction in the level is considered an improvement.

  • Percentage of Participants Who Achieve an Improvement of at Least 0.3 Units From Baseline in the HAQ Disability Index at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0 (without any difficulty) to 3 (unable to do). HAQ-DI=sum of worst scores in each domain divided by the number of domains answered for a total possible score of 0 (best) to 3 (worst).

  • Percentage of Participants Who Achieve an Improvement of at Least 0.3 Units From Baseline in the HAQ Disability Index at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]

    The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0 (without any difficulty) to 3 (unable to do).HAQ-DI=sum of worst scores in each domain divided by the number of domains answered for a total possible score of 0 (best) to 3 (worst).

    .


  • Area Under Curve (AUC) of the ACRn to Week 24 [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    The ACRn is defined as each patient's lowest percent improvement from Baseline of 3 measures: tender joint count (68 joints), swollen joint count (66 joints), and the improved score achieved in at least 3 of the 5 remaining ACR core components (physician global assessment, patient global assessment, pain, HAQ, and C-reactive protein or ESR, respectively). AUC of ACRn, a continuous variable, was calculated from Baseline to Week 24. A positive score change from Baseline indicated an improvement. The higher the ACRn score the better.

  • Area Under Curve (AUC) of the ACRn to Week 52 [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
    The ACRn is defined as each patient's lowest percent improvement from Baseline of 3 measures: tender joint count (68 joints), swollen joint count (66 joints), and the improved score achieved in at least 3 of the 5 remaining ACR core components (physician global assessment, patient global assessment, pain, HAQ, and C-reactive protein or ESR, respectively). AUC of ACRn, a continuous variable, was calculated from Baseline to Week 52. A positive score change from Baseline indicated an improvement. The higher the ACRn score the better.

  • Area Under Curve (AUC) of the ACRn Score at Week 104 [ Time Frame: 104 Weeks ] [ Designated as safety issue: No ]
    The ACRn is defined as each patient's lowest percent improvement from Baseline of 3 measures: tender joint count (68 joints), swollen joint count (66 joints), and the improved score achieved in at least 3 of the 5 remaining ACR core components (physician global assessment, patient global assessment, pain, HAQ, and C-reactive protein or ESR, respectively). AUC of ACRn, a continuous variable, was calculated from Baseline to Week 104. A positive score change from Baseline indicated an improvement. The higher the ACRn score the better.

  • Change From Baseline in Disease Activity Score (DAS28) at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity], and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement.

  • Change From Baseline in Disease Activity Score (DAS28) at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity], and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement.

  • Change From Baseline in Disease Activity Score (DAS28) at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
    The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity], and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement.

  • Percentage of Participants With DAS28 Good or Moderate EULAR Response at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]

    The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] , and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement.

    European League Against Rheumatism (EULAR) Good response: DAS28 ≤ 3.2 and a change from Baseline < -1.2.

    EULAR Moderate response: DAS28 >3.2 to ≤ 5.1 or a change from Baseline < -0.6 to ≥ -1.2.


  • Percentage of Participants With DAS28 Good or Moderate EULAR Response at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]

    The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm) [visual analog scale: 0=no disease activity to 100=maximum disease activity] , and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement.

    European League Against Rheumatism (EULAR) Good response: DAS28 ≤ 3.2 and a change from Baseline < -1.2.

    EULAR Moderate response: DAS28 >3.2 to ≤ 5.1 or a change from Baseline < -0.6 to ≥ -1.2.


  • Percentage of Participants With DAS28 Good or Moderate EULAR Response at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]

    The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm) [visual analog scale: 0=no disease activity to 100=maximum disease activity] , and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement.

    European League Against Rheumatism (EULAR) Good response: DAS28 ≤ 3.2 and a change from Baseline < -1.2.

    EULAR Moderate response: DAS28 >3.2 to ≤ 5.1 or a change from Baseline < -0.6 to ≥ -1.2.


  • Percentage of Participants With DAS28 Remission at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: Yes ]
    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). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 remission is defined as a DAS28 score <2.6.

  • Percentage of Participants With DAS28 Remission at Week 52 [ Time Frame: Week 52 ] [ Designated as safety issue: Yes ]
    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). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control.DAS28 Remission is defined as a DAS28 score <2.6.

  • Percentage of Participants With DAS28 Remission at Week 104 [ Time Frame: Week 104 ] [ Designated as safety issue: Yes ]
    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). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score <2.6.

  • Area Under Curve (AUC) of Disease Activity Score (DAS28) at Week 24 [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    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). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. Higher calculated AUC values are worse (indicate higher disease activity).

  • Area Under Curve (AUC) of Disease Activity Score (DAS28) at Week 52 [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
    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). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. Higher calculated AUC values are worse (indicate higher disease activity).

  • Area Under Curve (AUC) of Disease Activity Score (DAS28) at Week 104 [ Time Frame: 104 Weeks ] [ Designated as safety issue: No ]
    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). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. Higher calculated AUC values are worse (indicate higher disease activity).

  • Change From Baseline in Modified Total Sharp-Genant Score at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    Radiographs were taken of each hand and foot at Baseline and Week 24 and evaluated at a central reading service by two independent radiologists using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). The maximum total erosion score in the hands is 100 and in the feet 42, the maximum scores for joint space narrowing in the hands is 100 and in the feet 48. The maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score.

  • Change From Baseline in Modified Total Sharp-Genant Score at Week 80 [ Time Frame: Baseline, Week 80 ] [ Designated as safety issue: No ]
    Radiographs were taken of each hand and foot at Baseline and Week 80 and evaluated at a central reading service by two independent radiologists using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). The maximum total erosion score in the hands is 100 and in the feet 42, the maximum scores for joint space narrowing in the hands is 100 and in the feet 48. The maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score.

  • Change From Baseline in Erosion Score at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). A lower number change from Baseline indicated a better score.

  • Change From Baseline in Erosion Score at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). A lower number change from Baseline indicated a better score.

  • Change From Baseline in Erosion Score at Week 80 [ Time Frame: Baseline, Week 80 ] [ Designated as safety issue: No ]
    Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). A lower number change from Baseline indicated a better score.

  • Change From Baseline in Erosion Score at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
    Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). A lower number change from Baseline indicated a better score.

  • Change From Baseline in Joint Space Narrowing Score at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). A lower change from Baseline indicated a better score.

  • Change From Baseline in Joint Space Narrowing Score at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). A lower number change from Baseline indicated a better score.

  • Change From Baseline in Joint Space Narrowing Score at Week 80 [ Time Frame: Baseline, Week 80 ] [ Designated as safety issue: No ]
    Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). A lower number change from Baseline indicated a better score.

  • Change From Baseline in Joint Space Narrowing Score at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
    Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). A lower number change from Baseline indicated a better score.

  • Percentage of Participants With no Progression of Erosion at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). No progression of Erosion score was defined as a change from Baseline of less than or equal to zero.

  • Percentage of Participants With no Progression of Erosion at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). No progression of Erosion score was defined as a change from Baseline of less than or equal to zero.

  • Percentage of Participants With no Progression of Erosion at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
    Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). No progression of Erosion score was defined as a change from Baseline of less than or equal to zero.

  • Percentage of Participants With no Progression of Joint Space Narrowing at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). No progression of Joint Space Narrowing score was defined as a change from Baseline of less than or equal to zero.

  • Percentage of Participants With no Progression of Joint Space Narrowing at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). No progression of Joint Space Narrowing score is defined as a change from Baseline of less than or equal to zero.

  • Percentage of Participants With no Progression of Joint Space Narrowing at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
    Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). No progression of Joint Space Narrowing score is defined as a change from Baseline of less than or equal to zero.

  • Change From Baseline in HAQ Disability Index (HAQ-DI) at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    HAQ-DI is a self-completed questionnaire specific for RA. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. To Calculate HAQ-DI the patient must have a domain score for at least 6 of 8 domains. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score (in range 6-8) for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from baseline indicated improvement.

  • Change From Baseline in HAQ Disability Index at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
    HAQ-DI is a self-completed questionnaire specific for RA. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. To Calculate HAQ-DI the patient must have a domain score for at least 6 of 8 domains. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score (in range 6-8). Total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from Baseline indicated improvement.

  • Change From Baseline in Quality Life Short Form-36 (SF-36) Score at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from baseline indicates improvement.

  • Change From Baseline in SF-36 Score at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from Baseline indicates improvement.

  • Change From Baseline in SF-36 Score at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
    The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from Baseline indicated improvement.

  • Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Score at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the patient's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the patient's health status.

  • Change From Baseline in FACIT-F Score at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the patient's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the patient's health status.

  • Change From Baseline in FACIT-F Score at Week 104 [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
    FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the patient's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the patient's health status.

  • Change From Baseline in Rheumatoid Factor (RF) at Week 24 in Those Patients With Positive RF [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    Blood was collected for Rheumatoid Factor (RF) at Baseline and Week 24 and was analyzed at a central laboratory. RF level was reported in international units/milliliter (IU/mL). A positive RF= >15 IU/mL. A lower number change from Baseline indicated a better result.

  • Change From Baseline in Rheumatoid Factor (RF) at Week 52 in Those Patients With Positive RF [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    Blood was collected for Rheumatoid Factor (RF) at Baseline and Week 52 and was analyzed at a central laboratory. RF level was reported in international units/milliliter (IU/mL). A positive RF= >15 IU/mL. A lower number change from Baseline indicated a better result.

  • Change From Baseline in Rheumatoid Factor (RF) at Week 104 in Those Patients With Positive RF [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
    Blood was collected for Rheumatoid Factor (RF) at Baseline and Week 104 and was analyzed at a central laboratory. RF level was reported in international units/milliliter (IU/mL). A positive RF= >15 IU/mL. A lower number change from Baseline indicated a better result.

  • Time to Onset of ACR20 by Treatment Group [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Time in days until ACR20 response. ACR20 response was defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.

  • Time to Onset of ACR50 by Treatment Group [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Time in days until ACR50 response. ACR50 response was defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.

  • Time to Onset of ACR70 by Treatment Group [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Time in days until ACR70 response. ACR70 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.

  • Percentage of Participants Who Withdraw Due to Lack of Sufficient Therapeutic Response [ Time Frame: 104 Weeks ] [ Designated as safety issue: No ]
    Insufficient therapeutic response (patient not responding to the drug as assessed by the physician) was selected by the investigator as a reason that the patient withdrew from the study.

  • Percentage of Participants in Each Treatment Group Who Receive Escape Therapy [ Time Frame: 104 Weeks ] [ Designated as safety issue: No ]

    In Escape 1, participants in the Tocilizumab 4 mg/kg + Methotrexate and Tocilizumab 8 mg/kg + Methotrexate groups received tocilizumab 8 mg/kg as escape therapy. Participants in the Placebo + Methotrexate group received tocilizumab 4 mg/kg as escape therapy.

    In Escape 2, all participants received tocilizumab 8 mg/kg.


  • Percentage of Participants Who Achieved Remission According to the ACR Remission Criteria by Week 24 [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    The percentage of participants, who achieved ACR remission at any study visit up to Week 24. ACR remission required that all five of the following criteria were met for at least two consecutive months: morning stiffness < 15 minutes, no fatigue, no joint pain, no joint tenderness or pain on motion, no soft tissue swelling in joints or tendon sheaths, and ESR < 30 mm/hr for a female or 20 mm/hr for a male.

  • Percentage of Participants Who Achieved Remission According to the ACR Remission Criteria by Week 52 [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
    The percentage of participants, who achieved ACR remission at any study visit up to Week 52. ACR remission required that all five of the following criteria were met for at least two consecutive months: morning stiffness < 15 minutes, no fatigue, no joint pain, no joint tenderness or pain on motion, no soft tissue swelling in joints or tendon sheaths, and ESR < 30 mm/hr for a female or 20 mm/hr for a male.

  • Percentage of Participants Who Achieved Remission According to the ACR Remission Criteria by Week 104 [ Time Frame: 104 Weeks ] [ Designated as safety issue: No ]
    The percentage of participants who achieved ACR remission at any study visit up to Week 104. ACR remission required that all five of the following criteria were met for at least two consecutive months: morning stiffness < 15 minutes, no fatigue, no joint pain, no joint tenderness or pain on motion, no soft tissue swelling in joints or tendon sheaths, and ESR < 30 mm/hr for a female or 20 mm/hr for a male.

  • Percentage of Participants Who Achieved Complete Clinical Response at Week 52 [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
    Complete clinical response is defined as a continuous 6-month period of remission by ACR criteria [defined as five of the following criteria are met for at least two consecutive months: morning stiffness < 15 minutes, no fatigue, no joint pain, no joint tenderness or swelling, and ESR < 30 mm/hr for a female or 20 mm/hr for a male] and no radiographic progression [defined as change from baseline ≤ 0 in the total Sharp-Genant score, erosion score, and JSN score]. Patients who achieve a complete clinical response at any time in the study are counted as responders, even if the response is not maintained.

  • Percentage of Participants Who Achieved Complete Clinical Response at Week 104 [ Time Frame: 104 Weeks ] [ Designated as safety issue: No ]
    Complete clinical response is defined as a continuous 6-month period of remission by ACR criteria [defined as five of the following criteria are met for at least two consecutive months: morning stiffness < 15 minutes, no fatigue, no joint pain, no joint tenderness or swelling, and ESR < 30 mm/hr for a female or 20 mm/hr for a male] and no radiographic progression [defined as change from baseline ≤ 0 in the total Sharp-Genant score, erosion score, and JSN score].

  • End of Study: Percentage of Participants With ACR Response at Week 260 [ Time Frame: Baseline, Week 260 ] [ Designated as safety issue: No ]
    ACR20/50/70/90 response is defined as a ≥ 20/50/70/90% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.

  • End of Study: Percentage of Participants With DAS28 Remission at Week 260 [ Time Frame: Week 260 ] [ Designated as safety issue: No ]
    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). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score <2.6.

  • End of Study: Percentage of Participants With DAS28 Low Disease Activity (LDA) at Week 260 [ Time Frame: Week 260 ] [ Designated as safety issue: No ]
    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). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. LDA is defined as DAS28 ≤3.2.

  • End of Study: Percentage of Participants With DAS28 European League Against Rheumatism (EULAR) Good or Moderate Response at Week 260 [ Time Frame: Baseline, Week 260 ] [ Designated as safety issue: No ]
    The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm), and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement. EULAR Good response: DAS28 ≤ 3.2 and a change from Baseline < -1.2. EULAR Moderate response: DAS28 >3.2 to ≤ 5.1 or a change from Baseline < -0.6 to ≥ -1.2.

  • End of Study: Change From Baseline in Swollen Joint Count at Week 260 [ Time Frame: Baseline, Week 260 ] [ Designated as safety issue: No ]
    66 joints were assessed at Baseline and Week 260 for swelling and joints are classified as swollen/not swollen for a total possible swollen joint count of 0 (best) to 66 (worst). A negative change from Baseline indicated improvement.

  • End of Study: Change From Baseline in Tender Joint Count at Week 260 [ Time Frame: Baseline, Week 260 ] [ Designated as safety issue: No ]
    68 joints were assessed at Baseline and Week 260 for tenderness and joints are classified as tender/not tender for a total possible swollen joint count of 0 (best) to 68 (worst). A negative change from Baseline indicated improvement.

  • End of Study: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 260 [ Time Frame: Baseline, Week 260 ] [ Designated as safety issue: No ]
    HAQ-DI is a self-completed questionnaire specific for RA. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. To Calculate HAQ-DI the patient must have a domain score for at least 6 of 8 domains. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score (in range 6-8) for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from Baseline indicated improvement.

  • End of Study: Change From Baseline in the Patient's Global Assessment of Disease Activity Visual Analog Scale (VAS) at Week 260 [ Time Frame: Baseline, Week 260 ] [ Designated as safety issue: No ]
    The patient's global assessment of disease activity was assessed at Baseline and Week 104 using a 0 to 100 mm horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

  • End of Study: Change From Baseline in the Physician's Global Assessment of Disease Activity VAS at Week 260 [ Time Frame: Baseline, Week 260 ] [ Designated as safety issue: No ]
    The physician's global assessment of disease activity was assessed using a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

  • End of Study: Change From Baseline in the Patient's Pain VAS at Week 260 [ Time Frame: Baseline, Week 260 ] [ Designated as safety issue: No ]
    The patient assessed their pain at Baseline and Week 260 using a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change from Baseline indicated improvement.

  • End of Study: Percentage of Participants With Clinical Improvement in the FACIT-Fatigue Score at Week 260 [ Time Frame: Baseline, Week 260 ] [ Designated as safety issue: No ]
    FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the patient's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). Clinically relevant improvement is defined as a ≥5 change from Baseline.

  • End of Study: Percentage of Participants With Clinical Relevant Improvement in the SF-36 Score at Week 260 [ Time Frame: Baseline, Week 260 ] [ Designated as safety issue: No ]
    The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. Clinically relevant improvement is defined as a ≥5 change from Baseline.

  • End of Study: Change From Baseline in Total Sharp-Genant Score at Week 260 [ Time Frame: Baseline, Week 260 ] [ Designated as safety issue: No ]
    Radiographs were taken of each hand and foot at Baseline and Week 260 and evaluated at a central reading service by two independent radiologists using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint).The maximum total erosion score in the hands is 100 and in the feet 42, the maximum scores for joint space narrowing in the hands is 100 and in the feet 48. The maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score. The results were reported based on the treatment the patient was originally randomized to.

  • End of Study: Change From Baseline in Erosion Score at Week 260 [ Time Frame: Baseline, Week 260 ] [ Designated as safety issue: No ]
    Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot and were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best ) to 142 (worst). A lower number change from Baseline indicated a better score.

  • End of Study: Change From Baseline in Joint Space Narrowing Score at Week 260 [ Time Frame: Baseline, Week 260 ] [ Designated as safety issue: No ]
    Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). A lower number change from Baseline indicated a better score.


Enrollment: 1196
Study Start Date: January 2005
Study Completion Date: July 2012
Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: tocilizumab [RoActemra/Actemra]
4 mg/kg or 8 mg/kg IV/month every 4 weeks.
Other Names:
  • RoActemra
  • Actemra
Drug: Methotrexate
10-25 mg/week
Experimental: 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.
Drug: tocilizumab [RoActemra/Actemra]
4 mg/kg or 8 mg/kg IV/month every 4 weeks.
Other Names:
  • RoActemra
  • Actemra
Drug: Methotrexate
10-25 mg/week
Placebo Comparator: 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.
Drug: Placebo
IV/month
Drug: Methotrexate
10-25 mg/week

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00106535

  Hide Study Locations
Locations
United States, Alabama
Birmingham, Alabama, United States, 35233-7333
Huntsville, Alabama, United States, 35801
United States, Arizona
Scottsdale, Arizona, United States, 85251
Tucson, Arizona, United States, 85724
United States, California
Anaheim, California, United States, 92801
Long Beach, California, United States, 90806
Los Angeles, California, United States, 90095
San Diego, California, United States, 92108
San Francisco, California, United States, 94118
Santa Maria, California, United States, 93454
Torrance, California, United States, 90505
United States, Colorado
Boulder, Colorado, United States, 80304
Colorado Springs, Colorado, United States, 80910
Denver, Colorado, United States, 80230
United States, Florida
Aventura, Florida, United States, 33180
Fort Lauderdale, Florida, United States, 33334
Tampa, Florida, United States, 33614
West Palm Beach, Florida, United States, 33407
United States, Idaho
Boise, Idaho, United States, 83702
Coeur D'alene, Idaho, United States, 83814
Idaho Falls, Idaho, United States, 83404
Meridan, Idaho, United States, 83642
United States, Illinois
Chicago, Illinois, United States, 60612-3824
Rockford, Illinois, United States, 61103
United States, Indiana
Indianapolis, Indiana, United States, 46202-5100
United States, Kentucky
Lexington, Kentucky, United States, 40515
United States, Maryland
Frederick, Maryland, United States, 21702
Hagerstown, Maryland, United States, 21740
Wheaton, Maryland, United States, 20902
United States, Missouri
Saint Louis, Missouri, United States, 63131
St Louis, Missouri, United States, 63141
United States, Montana
Billings, Montana, United States, 59101
Missoula, Montana, United States, 59802
United States, Nevada
Reno, Nevada, United States, 89502
United States, New Hampshire
Dover, New Hampshire, United States, 03820
United States, New Jersey
Medford, New Jersey, United States, 08055
Voorhees, New Jersey, United States, 08043
United States, New York
Albany, New York, United States, 12206
Brooklyn, New York, United States, 11201
Lake Success, New York, United States, 11042
New York, New York, United States, 10016
Stony Brook, New York, United States, 11794-8161
United States, North Carolina
Asheville, North Carolina, United States, 28801
Charlotte, North Carolina, United States, 28211
Raleigh, North Carolina, United States, 27609
Wilmington, North Carolina, United States, 28401
United States, Ohio
Canton, Ohio, United States, 44718
United States, Oklahoma
Oklahoma City, Oklahoma, United States, 73109
Tulsa, Oklahoma, United States, 74135
United States, Oregon
Eugene, Oregon, United States, 97401
United States, Pennsylvania
Bethlehem, Pennsylvania, United States, 18015
Duncansville, Pennsylvania, United States, 16635
Philadelphia, Pennsylvania, United States, 19140
Wyomissing, Pennsylvania, United States, 19610
United States, South Carolina
Columbia, South Carolina, United States, 29204
United States, Tennessee
Nashville, Tennessee, United States, 37203
United States, Texas
Dallas, Texas, United States, 75231
San Antonio, Texas, United States, 78217
United States, Washington
Olympia, Washington, United States, 98502
Seattle, Washington, United States, 98104
United States, Wisconsin
Glendale, Wisconsin, United States, 53217
Australia
Adelaide, Australia, 5011
Malvern, Australia, 3144
Melbourne, Australia, 3168
New Lambton, Australia, 2305
Shenton Park, Australia, 6008
St. Leonards, Australia, 2139
Brazil
Porto Alegre, Brazil, 91350-200
Rio de Janeiro, Brazil, 20551-030
Sao Paulo, Brazil, 01221-020
Sao Paulo, Brazil, 04026-000
Sao Paulo, Brazil, 5403900
China
Beijing, China, 100044
Beijing, China, 100032
Nanjing, China, 210008
Shanghai, China, 200433
Shanghai, China, 200127
Denmark
Hellerup, Denmark, 2900
Odense, Denmark, 5000
Finland
Heinola, Finland, 18120
Helsinki, Finland, 00290
Oulu, Finland, 90029
Vantaa, Finland, 01400
France
Amiens, France, 80054
Bobigny, France, 93009
Bois Guillaume, France, 76233
Bordeaux, France, 33076
Le Kremlin Bicetre, France, 94270
Lille, France, 59037
Nice, France, 06202
Orleans, France, 45000
Paris, France, 75651
Paris, France, 75877
Strasbourg, France, 67098
Toulouse, France, 31059
Vandoeuvre-les-nancy, France, 54511
Greece
Athens, Greece, 15127
Athens, Greece, 15121
Athens, Greece, 11527
Heraklion, Greece, 71110
Italy
Brescia, Italy, 25123
Coppito, Italy, 67100
Firenze, Italy, 50139
Genova, Italy, 16132
Milano, Italy, 20157
Milano, Italy, 20122
Napoli, Italy, 80131
Padova, Italy, 35128
Pavia, Italy, 27100
Pisa, Italy, 56100
Reggio Emilia, Italy, 42100
Roma, Italy, 00161
Torino, Italy, 10128
Udine, Italy, 33100
Valeggio Sul Mincio, Italy, 37067
Varese, Italy, 21100
Verona, Italy, 37134
Mexico
Chihuahua, Mexico, 31000
Mexico City, Mexico, 03100
Mexico City, Mexico, 06726
Mexico City, Mexico, 07360
Mexico City, Mexico, 06700
Monterrey, Mexico, 64460
Obregon, Mexico, 85000
Norway
Haugesund, Norway, 5528
Lillehammer, Norway, 2609
Tromsø, Norway, 9038
Poland
Bydgoszcz, Poland, 85-168
Dzialdowo, Poland, 13-200
Elblag, Poland, 82-300
Kalisz, Poland, 62-800
Krakow, Poland, 30-510
Krakow, Poland, 30-119
Poznan, Poland, 60-218
Szczecin, Poland, 71-252
Ustron, Poland, 43-450
Warszawa, Poland, 02-637
Warszawa, Poland, 00-909
Puerto Rico
Ponce, Puerto Rico, 00716
San Juan, Puerto Rico, 00936-5067
South Africa
Cape Town, South Africa, 7500
Cape Town, South Africa, 7405
Cape Town, South Africa, 4001
Diepkloof, South Africa, 1862
Spain
Barcelona, Spain, 08036
Cádiz, Spain, 11009
Merida, Spain, 97500
Sabadell, Spain, 08208
Santander, Spain, 39008
Sevilla, Spain, 41009
Switzerland
Lausanne, Switzerland, 1011
St. Gallen, Switzerland, 9007
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided by Hoffmann-La Roche

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00106535     History of Changes
Other Study ID Numbers: WA17823
Study First Received: March 25, 2005
Results First Received: February 9, 2010
Last Updated: December 18, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Methotrexate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014