Please select the eligibility criteria that correspond to the clinical trial below.
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
Brief Summary: 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).


Options:
A: Inclusion Criteria:

* The subject has a history of inadequate response to at least 1, but no more than 4, of the following DMARDs: sulfasalazine, injectable gold, methotrexate, leflunomide, cyclosporine, or a thiopurine derivative (azathioprine or 6-mercaptopurine)

Exclusion Criteria:

* Current Therapy With Any DMARD Or Biologic
B: * Rheumatoid Arthritis (RA) for greater than 1 year from the time of initial diagnosis of RA.
* Participants must have been taking methotrexate for at least 3 months with at least a weekly dose of 15 mg.
C: Inclusion Criteria:

* Subject must have a diagnosis of rheumatoid arthritis based on the American College of Rheumatology Association
* The subject has active disease at both Screening and Baseline, as defined:

  * ≥4 joints tender or painful on motion, AND
  * ≥4 joints swollen;
* The subject must have at least one knee, one elbow, one wrist or two metacarpophalangeal joints with active synovitis suitable for biopsy by the shaver technique

Exclusion Criteria:

* No arthroscopy should have been performed in the past 3 months in the same joint that is to be biopsied in this study.
* No intra-articular steroids should have been injected in the joint to be biopsied in this study in the previous 3 months.
* Subjects with evidence of hematopoietic disorders or evidence of hemoglobin levels \< 9.0 gm/dL or hematocrit \< 30 % at screening visit or within the 3 months prior to baseline synovial biopsy.
* An absolute white blood cell (WBC) count of \< 3.0 x 109/L (\<3000/mm3) or absolute neutrophil count of \<1.2 X 109/L (\<1200/mm3) at screening visit or within the 3 months prior to baseline synovial biopsy.
* Thrombocytopenia, as defined by a platelet count \<100 x 109/L (\< 100,000/mm3) at screening visit or within the 3 months prior to baseline synovial biopsy.
* Estimated GFR less than 40 ml/min based on Cockcroft Gault calculation .
D: 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.

Answer: D