Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase IIIB Multicenter, Randomized, Double-Blind, Double-Dummy Study to Compare the Efficacy and Safety of Abatacept Administered Subcutaneously and Intravenously in Subjects With Rheumatoid Arthritis, Receiving Background Methotrexate, and Experiencing an Inadequate Response to Methotrexate
Brief Summary: The purpose of this study is to determine whether a weekly subcutaneous dose of abatacept yields clinical efficacy comparable to that of monthly intravenous doses of abatacept in participants with rheumatoid arthritis and an inadequate response to current methotrexate therapy.


Options:
A: 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
B: Key Inclusion Criteria:

* Meeting criteria of the American Rheumatism Association for the diagnosis of rheumatoid arthritis (RA) and the American College of Rheumatology functional Classes I, II, or III.
* Inadequate response (as deemed by investigator) to methotrexate taken for at least 3 months (12 weeks) at a stable dose (6 to 8 mg/week) for 28 days prior to randomization (Day 1).
* Stabilization requirements for concomitant therapy: Oral corticosteroid treatment reduced to the equivalent of ≤10 mg prednisolone daily for 28 days and stabilized for at least 25 of 28 days prior to treatment (Day 1). No intra-articular, intravenous, or intramuscular injections of corticosteroids were permitted within 28 days prior to randomization (Day 1.)
* Washout requirements: Participants receiving combination RA therapy had to discontinue the following therapies at least 28 days prior to treatment (Day 1):

disease-modifying antirheumatic drugs (DMARDs), such as gold (auranofin and aurothiomalate sodium), actarit, bucillamine, azathioprine, salazosulfapyridine, lobenzarit disodium, D-penicillamine, cyclophosphamide, mycophenolate mofetil, mizoribine; cyclosporin, tacrolimus, and other calcineurin inhibitors; and immunoadsorption columns.

* Disease Activity Requirements: At randomization (Day 1), participants had to meet the following disease activity criteria: Swollen joint count: 10 or more swollen joints (66 joint count); tender joint count: 12 or more tender joints (68 joint count); C reactive protein (CRP): ≥0.8 mg/dL (result from screening visit).
* For participants receiving methotrexate plus other DMARDs(washout of a combination therapy required): At screening visit, participants had to meet the following disease activity criteria: Swollen joint count: 6 or more swollen joints (66 joint count); tender joint count: 8 or more tender joints (68 joint count); CRP: no restriction on CRP (not applicable).
* After washout, at randomization (Day 1), participants must meet the following disease activity criteria: Swollen joint count-10 or more swollen joints (66 joint count) and tender joint count-12 or more tender joints (68 joint count) and CRP: ≥0.8 mg/dL (result from screening visit). For those whose screening period were longer than 4 weeks, CRP test needed to be performed on Day
* 28 to Day -3 (prior to treatment Day 1) to verify eligibility.

Key Exclusion Criteria:

* Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, pulmonary, cardiac, neurologic, or cerebral disease. Concomitant medical conditions that, in the opinion of the investigator, might place the participant at unacceptable risk for participation in this study.
* Female participants who had undergone breast cancer screening that was suspicious for malignancy, and in whom the possibility of malignancy could not be reasonably excluded following additional clinical, laboratory, or other diagnostic evaluations.
* History of cancer within the last 5 years (other than nonmelanoma skin cell cancers cured by local resection)
* Existing nonmelanoma skin cell cancers had been removed prior to the first administration. Participants with carcinoma in situ, treated with definitive surgical intervention prior to study entry were allowed to participate.
* Clinically significant drug or alcohol abuse
* Any serious acute bacterial infection (such as pneumonia or pyelonephritis unless treated and completely resolved with antibiotics)
* Serious, chronic, or recurrent bacterial infections (such as recurrent pneumonia, chronic bronchiectasis)
* Those at risk for tuberculosis (TB). Specifically, those with current clinical, radiographic, or laboratory evidence suggestive of active TB; history of active TB within the last 3 years, even if treated; history of active TB more than 3 years ago unless there was documentation that the prior anti-TB treatment was appropriate in type and duration; latent TB that was not successfully treated. Participants with a positive result on TB screening test indicative of latent TB were not eligible for the study unless active TB infection had been ruled out and treatment for latent TB with isoniazid had been initiated for at least 4 weeks prior to administration of the study drug and the participant had a negative finding for TB on a chest X-ray film at enrollment.
* Herpes zoster resolving less than 2 months prior to enrollment
* Current evidence (as assessed by the investigator) suggestive of active or latent bacterial or viral infections, including human immunodeficiency virus infection.
* Physical examination and laboratory test findings: Hepatitis B surface antigen-positive status; hepatitis C antibody-positive status. Any of the following laboratory values: Hemoglobin concentration: \<.5 g/dL; white blood cell count: \<3,000/μL (3\*10\^9/L); platelet count: \<100,000/mm\^3(100\*10\^9/L); serum creatinine: \>2 times upper limit of normal (ULN); serum alanine aminotransferase: \>2 ULN; serum aspartate aminotransferase: \>2 ULN.
* Prohibited treatments and/or therapies: Prior exposure to abatacept (CTLA4-Ig); prior RA treatment with any biologics, such as anti-tumor necrosis factor therapy; prior exposure to any investigational biologic not currently approved in Japan; exposure to any study medication in any other previous study within 4 weeks or 5 half-lives, whichever was longer; receipt of any live vaccines within 3 months of administration of study medication or scheduled to receive live vaccines.
C: Inclusion Criteria:

* Diagnosed with RA in accordance with the 1987 classification criteria of ACR
* Aged 20 to 75 years inclusive at enrolment (within 2 weeks before starting treatment with the investigational drug)
* Treated with MTX at ≥6 mg/week for at least 8 weeks immediately before enrolment
* Rheumatoid arthritis of duration ≤10 years
* DAS28-ESR ≥3.2 (within 2 weeks before starting treatment with the investigational drug)
* Having received and thoroughly understood an adequate explanation about participation in the study, patients who have personally and voluntarily provided written informed consent

Major exclusion criteria:

* Patients who were Steinbrocker Class IV.
* Patients who received leflunomide within 12 weeks, DMARDs other than MTX within 8 weeks , or tacrolimus within 4 weeks before the 1st TCZ infusion.
* Patients who previously received biologic DMARDs including TCZ.
D: 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.

Answer: D