Efficacy and Safety of Adalimumab and Methotrexate (MTX) Versus MTX Monotherapy in Subjects With Early Rheumatoid Arthritis (PREMIER)

• Number of Subjects Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 52 [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
  American College of Rheumatology 50% (ACR50) response. A subject was a responder if the following criteria were met: >= 50% improvement in tender joint count; >= 50% improvement in swollen joint count; and >= 50% improvement in at least 3 of the 5 parameters: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject's self-assessment of physical function (Disability Index of the Health Assessment Questionnaire [HAQ]), and acute phase reactant value (CRP). Subjects withdrawing early were non-responders.
  
  
• Change From Baseline in Modified Total Sharp Score (TSS) at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
  The modified TSS (mTSS) is a measure of change in joint health. Digitized images of radiographs of hands and feet obtained at screening and Week 52 were scored in a blinded manner. Joints were scored for erosions on a scale of 0 (no damage) to 5 and joint space narrowing on a scale of 0 (no damage) to 4. Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). An increase in mTSS from baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement.
  
  

• Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]

  Subjects assessed their ability to do the following tasks:

  1) dress/groom; 2)arise; 3) eat; 4) walk; 5) reach; 6) grip; 7) maintain hygiene; and 8) maintain daily activity. Subjects assessed their ability to do the tasks over the past week by marking responses on a questionnaire. Possible responses (scores) for each task: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score (range = 0 to 3). Negative mean changes from baseline in the overall score indicate improvement.

  
  
• Number of Subjects Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 104 [ Time Frame: Week 104 ] [ Designated as safety issue: No ]
  American College of Rheumatology 50% (ACR50) response. A subject was a responder if the following criteria were met: >= 50% improvement in tender joint count; >= 50% improvement in swollen joint count; and >= 50% improvement in at least 3 of the 5 parameters: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject's self-assessment of physical function (Disability Index of the Health Assessment Questionnaire [HAQ]), and acute phase reactant value (CRP). Subjects withdrawing early were non-responders.
  
  
• Change From Baseline in Modified Total Sharp Score (TSS) at Week 104 [ Time Frame: Baseline and Week 104 ] [ Designated as safety issue: No ]
  The modified TSS (mTSS) is a measure of change in joint health. Digitized images of radiographs of hands and feet obtained at screening and Week 104 were scored in a blinded manner. Joints were scored for erosions on a scale of 0 (no damage) to 5 and joint space narrowing on a scale of 0 (no damage) to 4. Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). An increase in mTSS from baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement.
  
  
• Number of Subjects Who Achieved Clinical Remission, Defined as a Disease Activity 28 (DAS28) Score < 2.6 at Week 52 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
  The DAS28 is validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C reactive protein, and general health were included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission.
  
  
• Change From Baseline in the Physical Component of the Short Form-36 Health Status Survey (SF-36®) at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
  The SF-36® determined subjects' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 comprise the physical component of the SF-36®. Scores on each item were summed and averaged (range = 0-100); increases from baseline indicate improvement.
  
  
• Number of Subjects Meeting ACR70 Response Criteria for 6 Continuous Months During the Double-blind Phase [ Time Frame: Any 6 continuous months from Baseline to Week 104 ] [ Designated as safety issue: No ]
  American College of Rheumatology 70% (ACR70) response. A subject was a responder if the following criteria were met: >= 70% improvement in tender joint count; >= 70% improvement in swollen joint count; and >= 70% improvement in at least 3 of the 5 parameters: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject's self-assessment of physical function (Disability Index of the Health Assessment Questionnaire [HAQ]), and acute phase reactant value (CRP). Subjects withdrawing early were non-responders.
  
  
• Change From Baseline in the Mental Component of the Short Form-36 Health Status Survey (SF-36®) at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
  The SF-36® determined subjects' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 5-8 comprise the mental component of the SF-36®. Scores on each item were summed and averaged (range = 0-100); increases from baseline indicate improvement.
  
  
• ACR20/50/70 by Visit [ Time Frame: Through end of Year 10 ] [ Designated as safety issue: No ]
  
• Change in HAQ Score by Visit [ Time Frame: Through end of Year 10 ] [ Designated as safety issue: No ]
  
• Change in DAS28 Score by Visit [ Time Frame: Through end of Year 10 ] [ Designated as safety issue: No ]
  
• DAS28 (DAS<2.6) and Low Disease Activity (DAS28<3.2) by Visit [ Time Frame: Through end of Year 10 ] [ Designated as safety issue: No ]
  
• Change in Sharp Score at Year 10 [ Time Frame: Year 10 ] [ Designated as safety issue: No ]
  
• Sharp Score Progression (Change in Sharp Score >0.5 and >0) [ Time Frame: Year 10 ] [ Designated as safety issue: No ]
  
• Composite Score of ACR50 Plus no Change in Sharp Score [ Time Frame: Through end of Year 10 ] [ Designated as safety issue: No ]
  
• Major Clinical Response Over Year 10 [ Time Frame: Year 10 ] [ Designated as safety issue: No ]
  
• Improvement in HAQ of at Least 0.5 by Visit [ Time Frame: Through end of Year 10 ] [ Designated as safety issue: No ]
  

This study has an initial 2-year double-blind treatment period followed by an open-label extension period up to 10 years in duration. The study was designed to assess the potential of adalimumab + MTX to improve signs and symptoms of disease and to inhibit radiographic progression in subjects with recent onset (disease duration less than 3 years) RA not previously treated with MTX.