Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Phase 3, Controlled, Double-Blind, Parallel-Group, Multicenter Study to Evaluate the Safety and Efficacy of Rituximab in Combination With Methotrexate (MTX) Compared to MTX Alone, in Methotrexate-Naive Patients With Active Rheumatoid Arthritis
Brief Summary: This is a phase III, randomized, controlled, double-blind, parallel group, international study in approximately 750 patients with active Rheumatoid Arthritis (RA) who are naive to Methotrexate (MTX) therapy. Rheumatoid Factor (RF)-positive and RF-negative patients will be enrolled and will be allocated equally between 3 treatment arms.


Options:
A: Inclusion criteria:

* Adult patients 18-80 years of age
* RA for ≥ 2 months;
* Receiving outpatient treatment
* Patients naive to, and considered to be candidates for, methotrexate treatment

Exclusion criteria:

* Rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA
* Inflammatory joint disease other than RA, or other systemic autoimmune disorder
* Diagnosis of juvenile rheumatoid arthritis, or RA before the age of 16
* Surgery within 12 weeks of study
* Previous treatment with any approved or investigational biologic agent for RA, an anti-alpha4-integrin antibody or co-stimulation modulator, or cell-depleting therapy
* Concurrent treatment with any biologic agent or DMARD other than methotrexate
B: Inclusion Criteria:

* Diagnosis of Rheumatoid Arthritis
* At least 3 months prior treatment with Methotrexate (MTX)
* At least 10 swollen joints and 12 tender joints and C-Reactive Protein of at least 1 mg/dl
* Washout required for other disease modifying anti-rheumatic drugs (DMARDS)

Exclusion Criteria:

* participants who have failed more than 3 DMARDs
* participants previously treated with an approved biologic drug
* History of cancer in the last 5 years
* Severe or recurrent bacterial infection
* Any previous or current medical conditions that are contraindications to the use of TNF blocking agents
* Women of Child Bearing Potential
C: Inclusion Criteria:

* Active rheumatoid arthritis
* Inadequate response to stably dosed methotrexate

Exclusion Criteria:

* Current therapy with any DMARD or biologic other than methotrexate
D: Inclusion Criteria:

* Must have a clinical diagnosis of rheumatoid arthritis for at least 6 months
* Must have at least 6 tender joints AND 6 swollen joints
* Has a C-reactive protein ≥ 1.0 mg/L OR Erythrocyte Sedimentation Rate (ESR) ≥ 28 mm/hr
* Baseline MRI must show evidence of synovitis in the wrist
* Must have screening laboratory tests within acceptable levels
* Women of childbearing potential and all men must agree to use a medically accepted method of contraception prior to entering the study and continue throughout study up to 6 weeks after study completion
* Must meet tuberculosis (TB) screening criteria
* Have received methotrexate therapy for ≥ 3 months; dose must be stable for at least 8 weeks
* If taking the a disease modifying anti-rheumatic drug (DMARD) in combination with methotrexate must be on a stable dose
* Must have a clinically acceptable 12 lead electrocardiogram (ECG)
* If taking oral corticosteroids must be on a stable dose equivalent to ≤10 mg of prednisone (or prednisolone) per day for ≥2 weeks
* If taking daily non-steroidal anti-inflammatory drug (NSAID) must be on a stable dose for ≥2 weeks; if taking NSAID on an as-needed basis must agree to discontinue use for at least 3 days and use only acetaminophen for breakthrough pain for 3 days before each MRI and clinic visit
* If received biological therapies, the last dose of these drugs was to be received ≥ 3 months prior to the baseline visit AND the reason for discontinuations was not for safety considerations OR lack of efficacy

Exclusion Criteria:

* Are pregnant, intend to become pregnant, or are breastfeeding
* Has inflammatory arthritis other than RA
* Has uncontrolled hypertension
* Has moderate or severe congestive heart failure
* Has a history of or current signs and/or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, cerebral, or psychiatric disease
* Has a history of demyelinating disease or symptoms suggestive of multiple sclerosis or optic neuritis
* Is currently participating in another clinical study or have participated in a clinical study (e.g., laboratory or clinical evaluation) within 4 weeks
* Has history of any tumor with the exception of adequately treated basal cell carcinoma or carcinoma in situ of the cervix
* Has a history of any latent or active granulomatous infection including histoplasmosis, or coccidiomycosis
* Had a non-tuberculous mycobacterial infection or opportunistic infection (e.g. cytomegalovirus, Pneumocystis carinii, aspergillosis) within 6 months
* Has a history of an infected joint prosthesis which has not been removed or replaced
* Has a known hypersensitivity to human immunoglobulin proteins or other components of infliximab
* Has received rituximab or natalizumab
* Has known claustrophobia or other contraindication to MRI
* Does not meet washout period guidelines for previous treatments/injections/vaccinations

Answer: A