Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double-blind Study of Safety and Reduction in Signs and Symptoms During Treatment With Tocilizumab Monotherapy Versus Methotrexate Monotherapy in Patients With Moderate to Severe Active Rheumatoid Arthritis
Brief Summary: This 2 arm study will assess the safety and efficacy of tocilizumab monotherapy versus methotrexate in patients with active rheumatoid arthritis (RA). Patients will be randomized to receive tocilizumab 8mg/kg iv every 4 weeks plus placebo po weekly, or methotrexate 7.5-20mg po weekly plus placebo iv every 4 weeks. The anticipated time on study treatment is 3-12 months and the target sample size is 500+ individuals.


Options:
A: Inclusion Criteria:

Patients 18 years of age or older who have moderate to severely active axial spondyloarthritis.

Diagnosis made by:Chronic low back pain (duration \> 3 months, onset \< 50 years of age)plus 3 out of the 6 following criteria (including two of the following three criteria: inflammatory back pain, positive for HLA-B27 and positive MRI showing acute inflammatory lesions in spine or ISG)

* Inflammatory back pain1
* Good or very good response to NSAIDs
* One or more of the following extraspinal manifestations: uveitis, peripheral arthritis, enthesitis
* HLA-B27 positive
* Positive MRI showing acute inflammatory lesions in spine or ISG
* Positive family history for SpA Active disease is defined as a BASDAI score of equal or more than 4, back pain score (BASDAI question 2) of equal or more than 4 despite concurrent NSAID therapy, or intolerance to NSAIDs.

Other inclusion criteria include:

If on prednisone, equal or less than 7.5 mg per day; stable for 4 weeks prior to baseline.

An evaluation for latent tuberculosis infection will be performed using a Mendel Mantoux Test with 10TE (PPD), reading a chest x-ray, which should have been performed within the last 12 weeks before inclusion, and history of exposure to infected subjects. Patients who have evidence of latent TB infection should be given prophylaxis in accordance with local guidelines (Isoniazid 300 mg with adequate substitution of vitamin B6 for 9 months or 600 mg Rifampicine for 6 months). The prophylaxis will start 4 weeks before adalimumab is administered. After 2 weeks of prophylaxis blood tests (liver enzymes, creatinine and blood count) will be obtained. Patients with documented prophylaxis in the past need not to repeat this treatment.

Women of child bearing potential must have a negative pregnancy test at study baseline and use an adequate method of contraception (including 3 months after study completion). Sexual active men must use an accepted method of contraception including 3 months after study completion.

Able to self-administer injectable drug supplies or have a caregiver who will do so.

Able to store injectable test article at 2° to 8° C.

Exclusion Criteria:

Definite ankylosing spondylitis (according to modified New York criteria, sacroiliitis ³ grade 2 bilaterally or grade 3 to 4 unilaterally) History of active tuberculosis (TB), histoplasmosis or listeriosis. History of positive HIV status. Positive serology for hepatitis B or C indicating active infection, in case of hepatitis B also if indicating chronic infection History of malignancy other than carcinoma in situ of the cervix or adequately treated non-metastatic squamous or basal cell skin carcinoma.

Antibiotic treatment within 3 weeks prior to screening. Treatment with biologicals within the last 12 weeks If on DMARDs a washout period of at least 4 weeks is necessary. If Leflunomide was discontinued, it should be stopped at least 3 months or should be washed out within 4 weeks before study start.

History of uncontrolled diabetes, unstable ischemic heart disease, active inflammatory bowel disease, active peptic ulcer disease, recent stroke (within 3 months), ongoing congestive heart failure, and any other condition which, in the opinion of the investigator, would put the subject at risk by participation in the protocol.

Female subjects who are pregnant or breast-feeding. Previous diagnosis or signs of demyelinating diseases History of systemic lupus erythematosusReceipt of any live (attenuated) vaccines within 4 weeks before screening visit Laboratory exclusions are: hemoglobin level \< 8,5 mg/dl, white blood cell count \< 3.5 x109/l, platelet count \< 125 x 109 /l, creatinine level \> 175 µmol/liver enzymes or alkaline phosphatase \>2 times the upper limit of normal.

Participation in trials of other investigational medications within 30 days of entering the study Clinical examination showing significant abnormalities of clinical relevance History or current evidence of abuse of "hard" drugs (e.g. cocaine/heroine) or alcoholism
B: Inclusion Criteria:

* adult patients at least 18 years of age with active RA for at least 3 months;
* 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 major surgery within 6 months after entering study;
* treatment with methotrexate (MTX) within 6 months of entering study;
* patients who have stopped previous MTX treatment due to toxicity or lack of response;
* women who are pregnant or breast-feeding.
C: Inclusion Criteria:

* Completed double-blind portion of the IM101064 study.
* Rheumatoid arthritis (RA) for greater than 1 year from the time of initial diagnosis
* American College of Rheumatology (ACR) functional class I, II, III
* Subjects currently or previously received an anti-TNF therapy at an approved labeled dose for at least 3 months

Exclusion Criteria:

* Subjects with active vasculitis of a major organ system (except subcutaneous rheumatoid nodules)
* History of cancer within the last 5 years (other than non-melanoma skin cell cancers cured by local resection)
D: Inclusion:

- Generally healthy of at least 18 years of age with active rheumatoid arthritis.

Exclusion:

- A history or presence of clinically important medical disease.

Answer: B