Please select the eligibility criteria that correspond to the clinical trial below.
Title: An Open-Label, Prospective Study of the Safety of Rituximab in Combination With Other Disease-Modifying Anti-Rheumatic Drugs in Subjects With Active Rheumatoid Arthritis
Brief Summary: This is a Phase III, open-label study of a total of approximately 560 subjects with active rheumatoid arthritis (RA) who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs). Enrollment in the study was conducted in two stages. In Stage I of the study, approximately 400 subjects receiving non-biological DMARDs (with the exception of methotrexate \[MTX\] monotherapy or MTX and leflunomide combination therapy) were enrolled. In Stage II of the study, approximately 160 subjects receiving a Federal Drug Administration-approved biological DMARD at the time of screening were enrolled.


Options:
A: Inclusion Criteria:

* Age 18-65 years.
* Diagnosis of rheumatoid arthritis (RA) for at least 6 months.
* Receiving treatment for RA on an outpatient basis.
* Use of methotrexate (MTX) at a dose of 10-25 mg/wk (oral \[PO\] or subcutaneous \[SC\]) for at least 12 weeks prior to Day 1, with the dose stable during the last 4 weeks prior to Day 1 (first day of the treatment period).
* If taking a background corticosteroid, use of the corticosteroid must be for at least 12 weeks prior to Day 1 at a stable dose during the last 4 weeks prior to Day 1.
* If taking one non-steroidal anti-inflammatory drug (NSAID), use of a stable dose for at least 2 weeks prior to Day 1.

Exclusion Criteria:

* Rheumatic autoimmune disease other than RA or significant systemic involvement secondary to RA; Sjogren's syndrome with RA is permitted.
B: Inclusion Criteria (Stage I):

* Male or female subjects, between 18 and 80 years of age, who have a documented diagnosis of active rheumatoid arthritis (RA) for ≥ 6 months
* Receiving treatment for RA on an outpatient basis
* Have had an inadequate response to at least one non-biological disease-modifying anti-rheumatic drug (DMARD) and have been receiving this DMARD(s) for ≥ 12 weeks prior to baseline, with stable dose greater than or equal to 4 weeks prior to baseline
* Demonstrated tolerability to currently prescribed DMARDs
* If taking a background corticosteroid, use of the corticosteroid must be at a stable dose during the 4 weeks prior to the first day of treatment with rituximab (Day 1)
* Use of one nonsteroidal anti-inflammatory drug (NSAID) is permitted if the dose is stable for ≥ 2 weeks prior to Day 1

Exclusion Criteria (Stage I):

* Rheumatic autoimmune disease other than RA or significant systemic involvement secondary to RA (including but not limited to vasculitis, pulmonary fibrosis, or Felty's syndrome)
* Functional Class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in Rheumatoid Arthritis
* History of or current inflammatory joint disease other than RA or other systemic autoimmune disorder
* Diagnosis of juvenile idiopathic arthritis, or juvenile RA, and/or RA before age 16 years
* Any surgical procedure, including bone/joint surgery/synovectomy (including joint fusion or replacement) within 12 weeks prior to baseline or planned within 24 weeks of enrollment
* Lack of peripheral venous access
* Significant cardiac or pulmonary disease (including obstructive pulmonary disease)
* Evidence of significant uncontrolled concomitant disease such as, but not limited to, nervous system, renal, hepatic, endocrine, or gastrointestinal disorders that, in the investigator's opinion, would preclude subject participation
* Primary or secondary immunodeficiency (history of or currently active), including known history of human immunodeficiency virus (HIV) infection
* Known active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 4 weeks of baseline or completion of oral antibiotics within 2 weeks prior to baseline
* History of medically significant opportunistic infection
* History of serious recurrent or chronic infection
* History of deep space/tissue infection within 52 weeks prior to baseline
* History of cancer, including solid tumors, hematologic malignancies, and carcinoma in situ (except basal cell and squamous cell carcinoma of the skin that have been excised and cured)
* History of significant cytopenias or other bone marrow disorders
* History of alcohol, drug, or chemical abuse within 24 weeks prior to baseline
* Pregnancy or lactation
* Neuropathies and neurovasculopathies that might interfere with pain evaluation
* Methotrexate (MTX) monotherapy at the time of screening
* Concurrent treatment with MTX and leflunomide in combination
* Concurrent treatment with any biologic agent
* Prior to Day 1, subjects will be discontinued from all DMARDs/combinations that are prohibited in the protocol
* History of a severe allergic or anaphylactic reaction to a biologic agent, or known hypersensitivity to any component of rituximab or to murine proteins
* Previous treatment with an anti-α4 integrin agent
* Previous treatment with any cell-depleting therapies, including investigational agents
* Receipt of any vaccine within 28 days prior to baseline
* Intolerance or contraindications to IV corticosteroids
* Receipt of IV immunoglobulin (IVIG) or Prosorba\<TM\> column within 6 months prior to baseline
* Any previous treatment with rituximab
* Positive hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody

Inclusion Criteria (Stage II):

* Male or female subjects, between 18 and 80 years of age, who have a documented diagnosis of active RA for ≥ 6 months, diagnosed according to the revised 1987 ACR criteria for the classification of RA
* Receiving treatment for RA on an outpatient basis
* Have had an inadequate response to at least one biologic DMARD and have been receiving this agent at screening and for ≥ 12 weeks prior to baseline, with stable dose greater than or equal to 4 weeks prior to baseline
* Have demonstrated tolerability to currently prescribed DMARDs/biologics
* If taking a background corticosteroid, use of the corticosteroid must be at a stable dose during the 4 weeks prior to baseline
* Use of one NSAID is permitted if the dose is stable for ≥ 2 weeks prior to baseline

Exclusion Criteria (Stage II):

* Rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA (including but not limited to vasculitis, pulmonary fibrosis, or Felty's syndrome)
* Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis
* History of, or current, inflammatory joint disease other than RA or other systemic autoimmune disorder
* Diagnosis of juvenile idiopathic arthritis, or juvenile RA, and/or RA before age 16 years
* Any surgical procedure, including bone/joint surgery/synovectomy (including joint fusion or replacement) within 12 weeks prior to baseline or planned within 24 weeks of randomization
* Lack of peripheral venous access
* Significant cardiac or pulmonary disease (including obstructive pulmonary disease)
* Evidence of significant uncontrolled concomitant disease such as, but not limited to, nervous system, renal, hepatic, endocrine or gastrointestinal disorders that, in the investigator's opinion, would preclude subject participation
* Primary or secondary immunodeficiency (history of or currently active), including known history of HIV infection
* Known active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of baseline or completion of oral antibiotics within 2 weeks prior to baseline
* History of medically significant opportunistic infection
* History of serious recurrent or chronic infection
* History of deep space/tissue infection within 52 weeks prior to baseline
* History of cancer, including solid tumors, hematologic malignancies, and carcinoma in situ (except basal cell and squamous cell carcinoma of the skin that have been excised and cured)
* History of significant cytopenias or other bone marrow disorders
* History of alcohol, drug, or chemical abuse within 24 weeks prior to baseline
* Pregnancy or lactation
* Neuropathies and neurovasculopathies that might interfere with pain evaluation
* Infliximab monotherapy at the time of screening (infliximab should be in combination with MTX)
* Concurrent treatment with MTX and leflunomide in combination
* Concurrent treatment with more than one biologic agent
* Prior to Day 1, subjects will be discontinued from all DMARDs/combinations that are prohibited in the protocol
* History of a severe allergic or anaphylactic reaction to a biologic agent, or known hypersensitivity to any component of rituximab or to murine proteins
* Previous treatment with an anti-α4 integrin agent
* Previous treatment with any cell-depleting therapies
* Treatment with any investigational agent within 28 days of baseline or 5 half-lives of the investigational drug (whichever is the longer)
* Receipt of any vaccine within 28 days prior to baseline
* Intolerance or contraindications to IV corticosteroids
* Receipt of IVIG or Prosorba\<TM\> column within 6 months prior to baseline
* Any previous treatment with rituximab
* Positive hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody
* Positive purified protein derivative (PPD) skin test not adequately treated according to Center for Disease Control (CDC) guidelines
C: Inclusion Criteria:

* adult patients \>=18 years of age;
* RA for \>=6 months;
* receiving outpatient treatment;
* inadequate response to methotrexate, having received and tolerated it for \>=12 weeks, with a stable dose for \>=4 weeks.

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 arthritis, or RA before the age of 16;
* previous treatment with \>1 biologic agent, any cell-depleting therapies, or concurrent treatment with any biologic agent or DMARD other than methotrexate.
D: Inclusion Criteria:

* adult patients 18-80 years of age with active RA;
* patients who participated in MabThera study WA17042, and completed to at least the Week 24 visit;
* eligible for re-treatment, based on clinical symptoms;
* patients of reproductive potential must be using reliable contraceptive methods.

Exclusion Criteria:

* patients who participated in MabThera study WA17042 but withdrew into the safety follow-up;
* current treatment with any other disease-modifying antirheumatic drug (apart from methotrexate), or any anti-TNFalfa, anti-IL1, or other biologic therapies;
* development of any new contraindications to receiving MabThera;
* women who are pregnant or breast-feeding.

Answer: B