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 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 regard to reduction of signs and symptoms, of tocilizumab versus placebo, both in combination with methotrexate (MTX). in patients with moderate to severe active rheumatoid arthritis (RA) who currently have an inadequate response to MTX. Patients wil be randomized to receive tocilizumab 4mg/kg iv, tocilizumab 8mg/mg iv, or placebo iv, every 4 weeks; all patients will also receive methotrexate 10-25mg weekly. The anticipated time on study treatment is 3-12 months, and the target sample size is 500+ individuals.


Options:
A: Inclusion Criteria:

* Diagnosis of Rheumatoid Arthritis (RA)
* Currently receiving a suboptimal response to a stable dose of methotrexate for treatment of Rheumatoid Arthritis (RA)
* Active Rheumatoid Arthritis (RA) at time of screening and baseline

Exclusion Criteria:

* Previous or current treatment with etanercept, other tumor necrosis factor-alpha inhibitors, or other biologic agents
* Concurrent treatment with a Disease Modifying Antirheumatic Drug (DMARD), other than methotrexate, at screening
* Receipt of any Disease Modifying Antirheumatic Drug (DMARD), other than methotrexate, within 3 months before screening
B: 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.
C: Inclusion Criteria:

1. Patients (more than 18 years) with rheumatoid arthritis according to the ACR classification criteria (1) who have had the diagnose \< 6 months.

2. Moderate to severe rheumatoid arthritis defined as DAS28 (CRP-based) \> 3.2.

3. Negative pregnancy test (serum HCG) for women of childbearing potential prior to trial start. (Non-fertile women are defined as postmenopausal for at least 1 year or surgical sterilisation (bilateral tubal ligation, bilateral oophorectomy or hysterectomy)). Fertile women included in the trial should use contraception during the entire trial period (i.e. one of the following methods: Oral contraception, intrauterine device (IUD), depot injection of progesterone, subdermal implantation, contraceptive vaginal ring, transdermal depot plaster). In addition, contraception should be used for a period of 150 days after any discontinuation of trial medicine.

4. Ability and willingness to inject the sc. injections him/herself or to have an assistant give the injections.

5. Ability and willingness to give written informed consent and to meet the requirements of the trial protocol.

Exclusion Criteria:

1. Persons with latent TB defined with a positive Mantoux test (\>12 mm for vaccinated and 6 mm for non-vaccinated), positive cultivation of mycobacteria in tissue samples, chest X-ray indicating TB,or other risk factors for activation of untreated latent TB, and persons not been given adequate TB prophylaxis according to the instructions of the department.

2. Active or recurrent infections or severe infections requiring hospitalization or treatment with i.v. antibiotics within the last 30 days or oral antibiotics within the last 14 days prior to inclusion

3. Positive serology for Hepatitis B or C indicating active infection.

4. Medical history with a positive HIV status (Check of HIV test upon suspicion).

5. Medical history with histoplasmosis or listeriosis.

6. Previous cancer or lymph proliferative disease except cases teated radically and have been without relapse for a minimum of 5 years.

Patients with previous squamous cell carcinoma, basal cell skin carcinoma or cervical dysplasia, who have been treated successfully and radically can be included.

7. Previous diagnosis or signs of demyelinized disease in the CNS system (e.g. optic neuritis, visual disorder, disturbed gait, facial paralysis, apraxia).

8. Severe renal insufficiency (creatinine clearance \< 35 ml/min - nomogram).

9. Affected liver function: Liver enzymes \> 2 x above normal limit value.

10. Clinical significant drug or alcohol abuse during the past year and/or current daily alcohol consumption.

11. Unstable diabetes, unstable ischemic heart disease, heart insufficiency (NYHA III-IV), active chronic inflammatory intestinal disease, recent cerebral apoplexia (within 3 months), chronic leg ulcer or any other condition (e.g. kateter a demeure)which according to the investigator imposes an increased risk to the subject, if he/she participates in the protocol.

12. Anticoagulant therapy.

13. Pregnancy or breast-feeding.

14. Other inflammatory rheumatic diseases.

15. Aggressive parvovirus B19 infection.

16. Previous treatment with one or more DMARDs.

17. Glucocorticosteroid treatment within the last 4 weeks (except nasal and inhalation steroids).

18. Contraindications for trial medicine.
D: Inclusion Criteria:

* Adult patient with established moderate to severe rheumatoid arthritis

Exclusion Criteria:

* All concomitant diseases or pathological conditions that could interfere and impact the assessment of the study treatment
* Previous clinical trials and previous biological therapy that could interfere with the results in the present clinical trials

Answer: B