Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized Clinical Trial to Study the Effects of Infliximab on Clinical Efficacy and Hand and Wrist Magnetic Resonance Imaging (MRI) in Patients With Active Rheumatoid Arthritis (RA)(Protocol No. P08136)
Brief Summary: This is a study to compare the effect of infliximab versus placebo on synovial inflammation as measured by dynamic contrast enhanced (DCE)-MRI of one wrist. The primary hypothesis is that over 14 weeks of therapy, the change from baseline in the volume transfer rate in enhancing synovium is larger due to treatment with infliximab than with placebo.


Options:
A: Key Inclusion Criteria:

* Presence of active clinical synovitis in at least 2 joints, 1 of which must have been a small joint, for a minimum of 8 weeks prior to screening
* Onset of persistent symptoms ≤ 2 years prior to screening
* Positive test result for anticyclic citrullinated peptides 2
* Methotrexate naive or with minimum exposure to methotrexate, defined as no more than 10 mg/week for ≤4 weeks and no methotrexate dose for 1 month prior to screening visit
* Biologic naive, including no treatment with an investigational biologic prior to screening
* Disease Activity Score 28 based on C-reactive protein score ≥3.2 at screening
* Withdrawal from any treatment with chloroquine, hydroxychloroquine, and/or sulfasalazine (wash-out) for a minimum of 28 days prior to randomization
* If receiving oral corticosteroids, on a stable low dose (≤ 10 mg/day prednisone equivalent) for at least 4 weeks
* Able to undergo magnetic resonance imaging

Key Exclusion Criteria:

* Meeting diagnostic criteria for other rheumatic disease (eg, lupus erythematosus)
* Treatment with an intravenous, intramuscular, or intraarticular corticosteroid within 4 weeks prior to randomization
* Scheduled for or anticipating joint replacement surgery
* Presence of concomitant illness likely to require systemic glucocorticosteroid therapy during the study, in the opinion of the investigator
* History of malignancy in the last 5 years
* Any serious bacterial infection within the last 3 months not treated or resolved with antibiotics, or any chronic or recurrent bacterial infection
* At risk for tuberculosis
* Evidence of active or latent bacterial or viral infection at the time of potential enrollment, including human immunodeficiency or herpes zoster virus or cytomegalovirus that resolved less than 2 months prior to enrollment
B: 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
C: Inclusion Criteria:

* Male and female, aged at least 18 years old at the Screening visit.
* A clear chest X-ray within 3 months prior to Baseline visit.
* A diagnosis of adult-onset RA (of at least six months duration but not longer than 15 years prior to Screening) as defined by the 1987 American College of Rheumatology classification criteria.
* Active RA disease at Screening and Baseline as defined by:

  * ≥9 tender joints.
  * ≥9 swollen joints. and fulfilling 1 of the following 2 criteria:
  * ≥30 mm/hour ESR (Westergren), or
  * CRP \>15 mg/L.
* Must have received a stable dose of MTX with or without folic acid for at least 3 months prior to Baseline visit. The minimum dose is 10 mg MTX weekly.
* Patient must be willing to attend for a Week 52 X-ray of the hands and feet even if they are no longer receiving study treatment but have not withdrawn their informed consent.

Exclusion Criteria:

* A diagnosis of any other inflammatory arthritis e.g., psoriatic arthritis or ankylosing spondylitis.
* A secondary, non-inflammatory type of arthritis (e.g. OA or fibromyalgia) that in the Investigator's opinion is symptomatic enough to interfere with evaluation of the effect of CDP870 on the patient's primary diagnosis of RA.
* A history of an infected joint prosthesis at any time with prosthesis still in situ.
* Does not meet exclusionary concomitant medication criteria.
* A history of a lymphoproliferative disorder including lymphoma or signs and symptoms suggestive of lymphoproliferative disease at any time.
* Patients at a high risk of infection in the Investigator's opinion (e.g. leg ulcers, indwelling urinary catheter and persistent or recurrent chest infections).
D: Inclusion Criteria:

* Patients received placebo in main double-blind study (P04280, NCT00202852)
* Patients received Infliximab-containing regimen showing clinical response at week 30 in main double-blind study (P04280)

\[Main double-blind study (P04280, NCT00202852) inclusion criteria\]

* Diagnosis of rheumatoid arthritis (RA) according to the revised 1987 criteria of the American Rheumatism Association (Arnett et al, 1988). The disease should have been diagnosed \>6 months prior to screening.
* Active disease at the time of screening and pre-infusion as defined by:

  * \>=6 swollen joints
  * \>=6 tender joints and
* 2 of the following:

  * morning stiffness \>=45 min
  * erythrocyte sedimentation rate (ESR) \>=28 mm/h
  * C-reactive protein (CRP) \>=20 mg/L
* Men and women, \>=18 to \<=75 years of age
* Men and women of childbearing potential must be using adequate birth control measures (abstinence, oral contraceptives, intrauterine device (IUD), barrier method with spermicide, or surgical sterilization) and should continue such precautions for 6 months after receiving the last infusion.
* Must have been using oral or parenteral MTX for \>3 months with no break(s) in treatment of \>2 weeks total during this period. Patients must have been on a stable dose of \>=12.5 mg/wk (maximum 20 mg/wk) for at \>4 weeks prior to screening.
* Must be on a stable dose of folic acid prophylaxis for \>4 weeks prior to screening.
* Patients using oral corticosteroids, must have been on a stable dose of \<=10 mg/day for \>4 weeks prior to screening. If currently not using corticosteroids the patient must have not received corticosteroids for \>4 weeks prior to screening.
* If using nonsteroidal anti-inflammatory drugs (NSAIDs), patients should have been on a stable dose for \>4 weeks prior to screening.
* The screening laboratory tests must meet the following criteria:

  * Hemoglobin \>=5.3 mmol/L (\>=8.5 g/dL), providing a low hemoglobin level is not due to nutritional deficiencies or due to diseases other than chronic RA
  * white blood cell (WBC) \>=3.5 x 10\^9/L (\>=3.5 x 10\^3/mm\^3)
  * Neutrophils \>=1.5 x 10\^9/L (\>=1.5 x 103/mm\^3)
  * Platelets \>=100 x 10\^9/L (\>=100 x 103/mm\^3)
  * Serum transaminase \<=2 times the upper limit of normal
  * Alkaline phosphatase levels \<=2 times the upper limit of normal
  * Serum creatinine \<=150 µmol/L (\<=1.7 mg/dL)
* Must be able to adhere to the study visit schedule and other protocol requirements.
* Must be capable of giving informed consent and the consent must have been obtained prior to any study procedures including wash-out period.

Exclusion Criteria:

* Exclusion criteria below of main double-blind study (P04280, NCT00202852)

\[Main double-blind study (P04280, NCT00202852) exclusion criteria\]

* Pregnant women, nursing mothers, or a planned pregnancy within 1.5 years of enrollment.
* Patients who are incapacitated, largely or wholly bedridden or confined to a wheelchair, and who have little or no ability for self-care.
* Patients who have any current systemic inflammatory condition with signs and symptoms that might confound the evaluations of benefit from infliximab, eg Lyme disease, or a rheumatic disease other than RA.
* Use of disease modifying anti-rheumatic drugs (DMARDs) other than MTX within 4 weeks prior to screening. (If a patient had prior exposure to leflunomide within the past 6 months, cholestyramine 8 g should be given 3 times daily for 11 days to rapidly lower the plasma level of leflunomide.)
* Use of intra-articular, i.m. or i.v. corticosteroids (including i.m. ACTH) within 4 weeks prior to screening.
* Have been previously treated with infliximab or genetic recombinant therapy with RA (e.g. etanercept, adalimumab)
* Treatment with any other therapeutic agent targeted at reducing TNF (eg, pentoxifylline or thalidomide) within the previous 3 months.
* Treatment with any investigational drug within the previous 3 months.
* Prior use of cyclophosphamide, nitrogen mustard, chlorambucil, or other alkylating agents.
* History of any clinically significant adverse reaction to murine or chimeric proteins, including but not limited to allergic reactions.
* History of infected joint prosthesis within previous 5 years.
* Serious infections, such as hepatitis, pneumonia, pyelonephritis in the previous 3 months.
* Chronic infectious disease such as chronic renal infection, chronic chest infection with bronchiectasis or sinusitis.
* Active tuberculosis (TB). Also excluded are patients who have evidence of latent TB (positive purified protein derivative \[PPD\] skin test or a history of latent TB) without adequate therapy for TB initiated prior to first infusion of study drug. Also excluded are patients with evidence of an old or latent TB infection without documented adequate therapy, if they will not be treated with antitubercular therapy during the trial. Patients with a current close contact with an individual with active TB will also be excluded. Additionally, patients who have completed treatment for active TB within the previous 2 years are now explicitly excluded from the trial. Patients with a household member who has a history of active pulmonary TB should have had a thorough evaluation for TB prior to study enrollment as recommended by a local infectious disease specialist or published local guidelines of TB control agencies. Also excluded are patients with opportunistic infections, including but not limited to evidence of active cytomegalovirus, active Pneumocystis carinii, aspergillosis, or atypical mycobacterial infection, etc, within the previous 6 months.
* Current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic or cerebral disease.
* History of lymphoproliferative disease including lymphoma or signs suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (such as nodes in the posterior triangle of the neck, infraclavicular, epitrochlear, or periaortic areas), or splenomegaly.
* Any current known malignancy or history of malignancy within the previous 5 years, except for squamous or basal cell carcinoma of the skin that have been treated with no evidence of recurrence.
* Patients with moderate or severe heart failure (New York Heart Association \[NYHA\] class III/IV).
* Patients with pre-existing or recent onset of central nervous system demyelinating disorders.
* Known recent substance abuse (drug or alcohol).
* Patients in whom multiple venipunctures are not feasible due to poor tolerability or lack of easy access.
* Have a known infection with HIV or known active hepatitis B/C infection (including associated chronic active hepatitis).

Answer: B