Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase 3 Randomized, Double-Blind, Active Comparator, Placebo-Controlled Study Of The Efficacy And Safety Of 2 Doses Of CP 690,550 In Patients With Active Rheumatoid Arthritis On Background Methotrexate
Brief Summary: This is a comparative study of CP 690,550, Humira (adalimumab) and placebo on background methotrexate in patients with Rheumatoid Arthritis. The study is intended to provide evidence of the efficacy and safety of CP 690,550 when dosed 5 mg and 10 mg twice a day on background methotrexate in adult patients with moderate to severe Rheumatoid Arthritis. It is intended to confirm the benefits of CP-690,550 in improving signs and symptoms and physical function that were observed in Rheumatoid Arthritis. An active comparator, adalimumab, is also included.


Options:
A: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

* Subjects who are considered methotrexate inadequate responders
* 10 or more swollen joints (66 joint count) and 12 or more tender joints (68 joint count)

Exclusion Criteria:

* Subjects who failed one or multiple anti-tumor necrosis factor (TNF) therapies
* Subjects who meet diagnostic criteria for any other rheumatic disease (e.g., lupus erythematous)
* Subjects with active vasculitis of a major organ system (except for subcutaneous rheumatoid nodules)
* Subjects with severe chronic or recurrent bacterial infections
* Subjects who have received treatment with rituximab

An Anti-TNF Failure Sub-study was initiated (recruited separately from Main study) using the same treatment as the Main study in order to assess the immunogenicity and safety in the Anti-TNF Failure population. The Sub-study terminated due to low recruitment and participants were permitted to roll into the LT Open Label Period.
B: Inclusion Criteria

1. Male and female subjects aged ≥18 years at the time of signing the Informed Consent Form.
2. Patients with a diagnosis of rheumatoid arthritis as per the ACR/EULAR 2010 classification criteria (Appendix 7) confirmed at least 24 weeks prior to the screening visit.
3. Patients who have failed conventional DMARD therapy as per NICE/BSR Guidelines (49) i.e. failure of at least 2 DMARDS including MTX.
4. Patients with persistent RA disease activity despite having been treated with a current initial TNFi agent for at least 12 weeks. Active RA defined as\*:

   1. Primary non-response: failing to improve DAS28 by \> 1.2 (Appendix 6) or failing to achieve DAS28 ≤ 3.2 within the first 12 to 24 weeks of starting the initial TNFi.

      • This may include patients that have shown a reduction in DAS28 of \> 1.2 but still demonstrate unacceptably high disease activity in the physician's judgement with evidence of an overall DAS28 of ≥ 3.2 OR
   2. Secondary non-response: defined as inefficacy to first TNFi (having demonstrated prior satisfactory response) as per clinician judgement; with intolerance not the reason for cessation of first TNFi.
5. MTX dose stable for 4 weeks prior to the screening visit and to be continued for the duration of the study.
6. Patients on NSAIDs and / or corticosteroids (oral prednisolone not exceeding 10mg daily) who have been on an unchanged regimen for at least 4 weeks prior to the screening visit and are expected to remain on a stable dose until the baseline assessments have been completed.
7. Provided written informed consent prior to any trial-specific procedures.

Exclusion Criteria

1. Major surgery (including joint surgery) within 8 weeks prior to the screening visit or planned major surgery within 52 weeks following randomization.
2. Patients with inflammatory joint disease of different origin, mixed connective tissue disease, Reiter's syndrome, psoriatic arthritis, systemic lupus erythematosus, or any arthritis with onset prior to 16 years of age.
3. Patients receiving doses of prednisolone \> 10mg/day within the 4 weeks prior to the screening visit.
4. Patients receiving intra-articular or intra-muscular steroid injections within 4 weeks prior to the screening visit.
5. Patients who have previously received more than 1 TNFi drug OR any other biological therapy for the treatment of RA.
6. Patients unable or unwilling to stop treatment with a prohibited DMARD (i.e synthetic DMARD aside from MTX e.g. oral or injectable gold, chloroquine, hydroxychloroquine, cyclosporine, azathioprine, leflunomide, sulphasalazine) prior to the start of protocol treatment.
7. Treatment with any investigational drug in the last 12 weeks prior the start of protocol treatment.
8. Patients with other co-morbidity including acute, severe infections, uncontrolled diabetes, uncontrolled hypertension, unstable ischaemic heart disease, moderate/severe heart failure (Class III/IV of the New York Heart Association (NYHA) functional classification system (79)), active bowel disease, active peptic ulcer disease, recent stroke (within 12 weeks before the screening visit), or any other condition which, in the opinion of the investigator, would put the patient at risk to participate in the study or would make implementation of the protocol difficult.
9. Patients with any major episode of infection requiring hospitalisation or treatment with IV antibiotics within 12 weeks of start of treatment protocol or oral antibiotics within 4 weeks of start of protocol treatment.
10. Patients at significant risk of infection, which in the opinion of the investigator would put the patient at risk to participate in the study (e.g. leg ulceration, indwelling urinary catheter, septic joint within 52 weeks (or ever if prosthetic joint still in situ)).
11. Patients with known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections including herpes zoster (for tuberculosis and Hepatitis B and C see below), but excluding fungal infections of nail beds as per clinical judgment.
12. Patients with untreated active current or latent tuberculosis (TB). Patients should have been screened for latent TB (as per BSR guidelines) within 24 weeks prior to the screening visit and, if positive, treated following local practice guidelines prior to the start of protocol treatment.
13. Patients with active current hepatitis B and/or C infection. Patients should have been screened for hepatitis B and C within 24 weeks prior to the screening visit and if positive, excluded from the study.
14. Primary or secondary immunodeficiency (history of or currently active) unless related to primary disease under investigation.
15. Pregnancy, lactation or women of child-bearing potential (WCBP) unwilling to use an effective birth control measure (Appendix 2) whilst receiving treatment and after the last dose of protocol treatment as indicated in the relevant SmPC/IB.
16. Men whose partners are of child-bearing potential but who are unwilling to use an effective birth control measure (Appendix 2) whilst receiving treatment and after the last dose of protocol treatment as indicated in the relevant SmPC/IB.
17. Patients with known significantly impaired bone marrow function as for example significant anaemia, leukopaenia, neutropaenia or thrombocytopaenia as shown by the following laboratory values at the time of the screening visit:

    * Haemoglobin \< 8.5 g/dl
    * Platelet count \< 100 x 109 / L
    * White blood cell count \< 2.0 x 109 / L
    * Neutrophil count \< 1 x 109 / L
18. Patients with known severe hypoproteinaemia at the time of the screening visit, e.g. in nephrotic syndrome or impaired renal function, as shown by:

    * Serum Creatinine \> 150 umol / L
C: Inclusion Criteria:

* Patients diagnosed with rheumatoid arthritis at least 3 months prior to registration and who are definitely identified as having rheumatoid arthritis, at the time of informed consent, according to the criteria for classification established by the American College of Rheumatology (1987)
* Patients in whom MTX therapy (\>= 6 mg/week) was started more than 3 months before the first administration and who have been treated with MTX at a stable dose (6-8 mg/week) for at least 4 weeks before the first administration
* Patients having at least 4 swollen joints and at least 4 tender joints at the time of registration and immediately before the first administration.

Exclusion Criteria:

* Patients with a history of hypersensitivity to human immunoglobulin proteins or other ingredients of golimumab
* Patients who have previously experienced or are suffering from any of the following diseases: (i) Collagen diseases other than rheumatoid arthritis, (ii) Latent or active granulomatous infections such as histoplasmosis and coccidioidomycosis, (iii) Felty syndrome, etc
* Patients with a severe, advanced, or poorly controlled disease in any of the kidney, liver, blood, gastrointestinal system, endocrine system, lung, heart, nervous system, psychiatric system, and brain.
D: Inclusion Criteria:

* The patient has a diagnosis of RA based upon the American College of Rheumatology (ACR) 1987 Revised Criteria.
* The patient must have had an inadequate response to methotrexate and have active disease, as defined by both: ≥6 joints tender or painful on motion; and ≥6 joints swollen; and fulfills 1 of the following 2 criteria at Screening: 1.ESR (Westergren method) \>28 mm in the local laboratory. 2. CRP \>7 mg/L in the central laboratory.
* No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis.
* The patient must have been on a stable dose of 7.5 mg to 25 mg weekly of methotrexate and washed out of all other DMARDs.

Exclusion Criteria:

* Blood dyscrasias including confirmed: 1. Hemoglobin \<9 g/dL or Hematocrit \<30%; 2. White blood cell count \<3,000 cu.mm. Absolute neutrophil count \<1,200 cu.mm; 4. Platelet count \<100,000/L
* History of any other autoimmune rheumatic disease other than Sjogren's syndrome
* No malignancy or history of malignancy.
* History of infection requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator, within the 6 months prior to the first dose of study drug
* Patients who have failed any TNFi for either lack of efficacy or a TNFi mechanism related adverse event.
* Patients who have previously received adalimumab therapy for any reason.
* Patients who are contraindicated for treatment with adalimumab in accordance with the approved local label.
* Patients meeting the New York Heart Association Class III and Class IV Congestive Heart failure

Answer: D