A Study of the Safety and Efficacy of Golimumab in Subjects With Rheumatoid Arthritis That Are Methotrexate-naive

• Number of Participants Who Achieved American College of Rheumatology (ACR) 50 Response at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  ACR 50 response is an improvement of greater than or equal to 50% in both tender and swollen joint count and in 3 to 5 assessments- patient's assessment of pain visual analog scale (VAS) (0 [no pain] to 10 [worst pain]); patient's and physician's global assessment of disease activity VAS scales: overall disease activity, (0 [very well] to 10 [very poor] and 0 [no arthritis activity] to 10 [extremely active], respectively); Health Assessment Questionnaire (HAQ): 20-questions on life activities (0 [no difficulty] to 3 [inability to perform a task];and assessment of C-reactive protein [CRP].
• Change From Baseline in Total Van Der Heijde Modified Sharp (vdH-S) Score at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
  Total vdH-S score is sum of joint erosion score and joint-space narrowing (JSN) score. Joint erosion score summarizes erosion severity in 32 joints of hands and 12 joints of feet. Each joint scored from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Maximal erosion score is 280. JSN score summarizes severity of JSN in 30 joints of hands and 12 joints of feet. Assessment of JSN, including subluxation, is scored from 0 (normal) to 4 (bony ankylosis or complete luxation). Maximal JSN score is 168. Thus, the worst possible vdH-S score is 448.

• Number of Participants Who Achieved American College of Rheumatology (ACR) 20 Response at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  ACR 20 response is an improvement of greater than or equal to 20% in both tender and swollen joint count and in 3 to 5 assessments- patient's assessment of pain visual analog scale (VAS) (0 [no pain] to 10 [worst pain]); patient's and physician's global assessment of disease activity VAS scales: overall disease activity, (0 [very well] to 10 [very poor] and 0 [no arthritis activity] to 10 [extremely active], respectively); Health Assessment Questionnaire (HAQ): 20-questions on life activities (0 [no difficulty] to 3 [inability to perform a task];and assessment of C-reactive protein [CRP].
• Number of Patients With Abnormal Baseline C-reactive Protein (CRP) Who Achieved American College of Rheumatology (ACR) 50 Response at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  ACR 50 response is an improvement of greater than or equal to 50% in both tender and swollen joint count and in 3 to 5 assessments- patient's assessment of pain visual analog scale (VAS) (0 [no pain] to 10 [worst pain]); patient's and physician's global assessment of disease activity VAS scales: overall disease activity, (0 [very well] to 10 [very poor] and 0 [no arthritis activity] to 10 [extremely active], respectively); Health Assessment Questionnaire (HAQ): 20-questions on life activities (0 [no difficulty] to 3 [inability to perform a task];and assessment of CRP.
• Change From Baseline in Total Van Der Heijde Modified Sharp (vdH-S) Score at Week 52 in Patients With Abnormal C-reactive Protein (CRP Greater Than 1.0 mg/dL) at Baseline [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
  Total vdH-S score is sum of joint erosion score and joint-space narrowing (JSN) score. Joint erosion score summarizes erosion severity in 32 joints of hands and 12 joints of feet. Each joint scored from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Maximal erosion score is 280. JSN score summarizes severity of JSN in 30 joints of hands and 12 joints of feet. Assessment of JSN, including subluxation, is scored from 0 (normal) to 4 (bony ankylosis or complete luxation). Maximal JSN score is 168. Thus, the worst possible vdH-S score is 448.

The purpose of this study is to evaluate the efficacy and safety of golimumab, alone or in combination with methotrexate, as compared to methotrexate alone in rheumatoid arthritis subjects who have not been previously treated with methotrexate.

Golimumab is a fully human protein (antibody) which binds to tumor necrosis factor (TNFa). TNFa is increased in patients with rheumatoid arthritis (RA), and plays a major role in causing the joint pain, swelling, and damage from RA. Other marketed drugs that target TNFa (anti-TNFa drugs) have been shown to be effective in reducing the symptoms, signs, and joint damage of RA, but have limitations with respect to safety and ease of use. This is a randomized, double-blind, placebo-controlled trial of the efficacy and safety of a new anti-TNFa drug, golimumab, at 2 doses, injected under the skin every 4 weeks, alone or in combination with methotrexate, compared with methotrexate alone, in subjects with active RA who have not been previously treated with methotrexate. The study hypothesis is that golimumab, alone or in combination with methotrexate, will be more effective in treatment of RA than methotrexate alone, as measured by the American College of Rheumatology (ACR) response criteria and change from baseline in van der Heide Modified Sharp (vdH-S) score, without causing unacceptable significant adverse effects. The ACR response criteria were designed to determine the percentage of subjects who have achieved a certain level of improvement in their signs and symptoms of rheumatoid arthritis. The vdH-S score is a measurement of the amount of joint damage in a subject as seen by x-ray. Other secondary measures of effectiveness include the Health Assessment Questionnaire (HAQ), which is a series of questions that measure a subject's impairment in physical function caused by RA. Golimumab 50 mg or 100 mg, or placebo injections under the skin every 4 weeks until Week52. Methotrexate (MTX) or placebo capsules will be given in addition. At Week52, subjects on MTX alone with joint pain or swelling get golimumab 50mg, and all subjects receive golimumab for about 4 more years.

• Biological: golimumab
  50 mg sc injections every 4 wks from wk0-48 (Wk 28 if early escape);Methotrexate - 10-20 mg for up to 5 years; Golimumab - If early escape, 100 mg beginning at wk 28 for up to 5 yrs; Golimumab - Dr's discretion after unblinding, dose adjust from 50 to100 mg
• Drug: placebo; methotrexate
  SC injections every 4 wks from wk0 to wk 48 (unless early escape at wk 28);methotrexate-10-20mg for up to 5 years;golimumab-If early escape, 50mg sc injection every 4 wks from wk 28 up to 5 yrs; golimumab-Dr's discretion after unblinding, dose adjust from 50 to 100 mg
• Biological: Golimumab
  100 mg sc injections every 4 wks from wk 0 up to 5 yrs; Methotrexate - 10-20 mg for up to 5 years
• Drug: golimumab; methotrexate
  100mg sc injection every 4 wks for up to 5 yrs;methotrexate- 4-8 capsules weekly during blinded period;methotrexate - If early escape may start 10mg weekly during blinded period; methotrexate - Dr's discretion, adjust weekly dose after unblinding

• Experimental: 004
  Golimumab 100 mg sc injections every 4 wks from wk 0 up to 5 yrs; Methotrexate - 10-20 mg for up to 5 years
  Intervention: Biological: Golimumab
• Experimental: 003
  golimumab 50 mg sc injections every 4 wks from wk0-48 (Wk 28 if early escape);Methotrexate - 10-20 mg for up to 5 years; Golimumab - If early escape, 100 mg beginning at wk 28 for up to 5 yrs; Golimumab - Dr's discretion after unblinding, dose adjust from 50 to100 mg
  Intervention: Biological: golimumab
• Placebo Comparator: 001
  placebo; methotrexate SC injections every 4 wks from wk0 to wk 48 (unless early escape at wk 28);methotrexate-10-20mg for up to 5 years;golimumab-If early escape, 50mg sc injection every 4 wks from wk 28 up to 5 yrs; golimumab-Dr's discretion after unblinding, dose adjust from 50 to 100 mg
  Intervention: Drug: placebo; methotrexate
• Experimental: 002
  golimumab; methotrexate 100mg sc injection every 4 wks for up to 5 yrs;methotrexate- 4-8 capsules weekly during blinded period;methotrexate - If early escape may start 10mg weekly during blinded period; methotrexate - Dr's discretion, adjust weekly dose after unblinding
  Intervention: Drug: golimumab; methotrexate

Inclusion Criteria:

• Have a diagnosis of rheumatoid arthritis (RA) (according to the revised 1987 criteria of the ACR) for at least 3 months prior to first administration of study agent
• Are methotrexate (MTX)-naïve (ie, have not received more than 3 weekly doses of MTX for RA at any time)
• Have active RA as defined by persistent disease activity with at least 4 swollen and 4 tender joints, at the time of screening and baseline, and at least 2 of the following 4 criteria: a) C-reactive protein (CRP) >=1.5 mg/dL at screening or erythrocyte sedimentation rate (ESR) by Westergren method of >= 28 mm in the first hour at screening or baseline, b)Morning stiffness of >= 30 minutes at screening and baseline, c)Bone erosion by x-ray and/or MRI prior to first administration of study agent, d)Anti-cyclic citrullinated peptide (anti-CCP) antibody-positive or rheumatoid factor (RF) positive at screening
• If using oral corticosteroids, must be on a stable dose equivalent to <= 10 mg of prednisone/day for at least 2 weeks prior to first administration of study agent.

Exclusion Criteria:

• Can not have inflammatory diseases other than RA that might confound the evaluation of the benefit of golimumab therapy
• No treatment with disease-modifying anti-rheumatic drugs (DMARDs)/systemic immunosuppressives during the 4 weeks prior to the first administration of study agent
• No prior treatment with biologic anti-TNF drugs (infliximab, etanercept, adalimumab)
• No history of, or ongoing, chronic or recurrent infectious disease
• No serious infection within 2 months prior to first administration of study agent.