Please select the eligibility criteria that correspond to the clinical trial below.
Title: A 12-week Randomized, Double-blind, Multicenter Pilot Study to Evaluate the Effect of Etanercept 100 mg and 50 mg Weekly in Subjects With Ankylosing Spondylitis
Brief Summary: The purpose of this study was to evaluate efficacy and safety of etanercept 100 mg (50 mg twice a week) compared with 50 mg once a week in adult subjects with ankylosing spondylitis (AS) and previous failure to usual practice therapies in Spain.


Options:
A: Inclusion Criteria:

* Have had a diagnosis of definite Akylosing Spondylitis for at least 3 months prior to screening
* Have active disease with spinal pain
* receiving or intolerant to standard anti-inflammatory agents

Exclusion Criteria:

* Have Rheumatoid Arthritis, systemic lupus erythematosus, or other inflammatory rheumatic disease
* Have a documented history of fibromyalgia
* Have total ankylosis
B: Inclusion Criteria:

Patients 18 years of age or older who have moderate to severely active axial spondyloarthritis.

Diagnosis made by:Chronic low back pain (duration \> 3 months, onset \< 50 years of age)plus 3 out of the 6 following criteria (including two of the following three criteria: inflammatory back pain, positive for HLA-B27 and positive MRI showing acute inflammatory lesions in spine or ISG)

* Inflammatory back pain1
* Good or very good response to NSAIDs
* One or more of the following extraspinal manifestations: uveitis, peripheral arthritis, enthesitis
* HLA-B27 positive
* Positive MRI showing acute inflammatory lesions in spine or ISG
* Positive family history for SpA Active disease is defined as a BASDAI score of equal or more than 4, back pain score (BASDAI question 2) of equal or more than 4 despite concurrent NSAID therapy, or intolerance to NSAIDs.

Other inclusion criteria include:

If on prednisone, equal or less than 7.5 mg per day; stable for 4 weeks prior to baseline.

An evaluation for latent tuberculosis infection will be performed using a Mendel Mantoux Test with 10TE (PPD), reading a chest x-ray, which should have been performed within the last 12 weeks before inclusion, and history of exposure to infected subjects. Patients who have evidence of latent TB infection should be given prophylaxis in accordance with local guidelines (Isoniazid 300 mg with adequate substitution of vitamin B6 for 9 months or 600 mg Rifampicine for 6 months). The prophylaxis will start 4 weeks before adalimumab is administered. After 2 weeks of prophylaxis blood tests (liver enzymes, creatinine and blood count) will be obtained. Patients with documented prophylaxis in the past need not to repeat this treatment.

Women of child bearing potential must have a negative pregnancy test at study baseline and use an adequate method of contraception (including 3 months after study completion). Sexual active men must use an accepted method of contraception including 3 months after study completion.

Able to self-administer injectable drug supplies or have a caregiver who will do so.

Able to store injectable test article at 2° to 8° C.

Exclusion Criteria:

Definite ankylosing spondylitis (according to modified New York criteria, sacroiliitis ³ grade 2 bilaterally or grade 3 to 4 unilaterally) History of active tuberculosis (TB), histoplasmosis or listeriosis. History of positive HIV status. Positive serology for hepatitis B or C indicating active infection, in case of hepatitis B also if indicating chronic infection History of malignancy other than carcinoma in situ of the cervix or adequately treated non-metastatic squamous or basal cell skin carcinoma.

Antibiotic treatment within 3 weeks prior to screening. Treatment with biologicals within the last 12 weeks If on DMARDs a washout period of at least 4 weeks is necessary. If Leflunomide was discontinued, it should be stopped at least 3 months or should be washed out within 4 weeks before study start.

History of uncontrolled diabetes, unstable ischemic heart disease, active inflammatory bowel disease, active peptic ulcer disease, recent stroke (within 3 months), ongoing congestive heart failure, and any other condition which, in the opinion of the investigator, would put the subject at risk by participation in the protocol.

Female subjects who are pregnant or breast-feeding. Previous diagnosis or signs of demyelinating diseases History of systemic lupus erythematosusReceipt of any live (attenuated) vaccines within 4 weeks before screening visit Laboratory exclusions are: hemoglobin level \< 8,5 mg/dl, white blood cell count \< 3.5 x109/l, platelet count \< 125 x 109 /l, creatinine level \> 175 µmol/liver enzymes or alkaline phosphatase \>2 times the upper limit of normal.

Participation in trials of other investigational medications within 30 days of entering the study Clinical examination showing significant abnormalities of clinical relevance History or current evidence of abuse of "hard" drugs (e.g. cocaine/heroine) or alcoholism
C: Inclusion criteria:

1. Diagnosis of ankylosing spondylitis, as defined by Modified New York Criteria for Ankylosing Spondylitis.
2. Maintained inflammatory activity for more than 12 weeks defined by:·Axial forms: BASDAI higher than or equal to 4 (0-10) and at least one of the following parameters:. Global assessment of the disease by the patient higher than or equal to 4 (On a scale 0-10). Spinal pain higher than or equal to 4 on a visual analogue scale (VAS). Increase in erythrocyte sedimentation rate (ESR) and/or CRP above the normality parameters established by the laboratory.·Peripheral forms: Arthritis or enthesitis higher than or equal to 1 site and at least one of the following:. Global assessment of the disease by the patient higher than or equal to 4 (on a scale 0-10). Increase in erythrocyte sedimentation rate (ESR) and/or CRP above the normality parameters established by the laboratory
3. Failure to treatment: Failure to at least 2 NSAIDs at maximum recommended dose during at least 3 months (or a shorter time in case of intolerance, toxicity or contraindication).·In cases of ankylosing spondylitis with peripheral joint involvement, salazopyrine should have been used at a dose of 2-3 g per day and/or methotrexate (15 mg/week) for 4 months (or a shorter time in case of intolerance, toxicity or contraindication). In case of oligoarticular or localized involvement in enthesis: lack of response, at the discretion of the investigator, to local infiltrations and/or synoviorthesis.
4. Be between 18-70 years of age
5. Negative result of a pregnancy test in serum in screening visit and in urine in baseline visit, done in all women, except those surgically sterilized and those who have at least one year of menopause.
6. Sexually active women of childbearing potential must use medically acceptable contraceptive methods, including oral, injectable or implantable contraceptive methods, intrauterine devices or properly used barrier contraception. A woman of childbearing potential is defined as one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives.
7. Men who are not surgically sterile should agree to use reliable contraceptive methods during the study.
8. Ability to reconstitute the drug and self-inject it or have a person who can do so.
9. Capability to understand and voluntarily give written informed consent that is signed and dated, before any specific procedure of the protocol is performed.
10. Ability to store injectable test article at 2º to 8º C.

Exclusion criteria:

1. Contraindications for treatment with anti-TNF
2. Complete ankylosis of spine
3. Onset of treatment with DMARDs in the 4 weeks prior to baseline (SSZ, MTX and HCQ are permitted if the administrated dose has been maintained stable in the 4 weeks prior to baseline). Furthermore, patients with a dose of prednisone \>10 mg/d or equivalent or modified in the 2 weeks prior to the baseline visit, those in whose infiltration has been performed with intraarticular corticosteroids has been performed in the 4 weeks prior to the screening visit and those who follow treatment with more than one NSAID in the 2 weeks prior to the baseline visit are excluded.
4. Previous treatment with other TNF inhibitors and other biological drugs
5. Abnormalities in hematology profiles defined by:

   * leukocytes lower than or equal to 3.5 x 10 exponent 9 /L
   * hemoglobin lower than or equal to 8.5 g/L or 5.3 mmol/L
   * hematocrit lower than or equal to 27%
   * platelets lower than or equal to 125 x 10 exponent 9 /L
   * serum creatinine higher than or equal to 175 mmol/L
   * aspartate aminotransferase and alanine aminotransferase higher than or equal to 2 times the upper limit of normality
6. Important concomitant medical conditions, such as:-Class III or IV congestive heart failure according to New York Heart Association classification-Uncontrolled arterial hypertension (defined as screening systolic blood pressure \> 160 mm Hg or screening diastolic blood pressure \> 100 mm Hg)-Myocardial infarction within 12 months of the screening visit or unstable angina-Severe pulmonary disease requiring hospitalization or oxygen therapy-Diagnosis of multiple sclerosis or other central nervous system demyelinating disease -Presence or history of confirmed blood dyscrasias-Cancer or history of cancer (other than resected cutaneous basal cell or squamous cell carcinoma)-Serious infection (infection requiring hospitalization and/or intravenous antibiotics) within 1 month of administration of test article administration or active infection at screening or history of recurrent or chronic infection-Open cutaneous ulcers-Patients with known chronic infections as positivity to HIV, hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) -Active tuberculosis infection (local guidelines for appropriate screening and treatment of tuberculosis in the setting of anti-TNF therapy must be followed)- Any condition that, in the investigator's judgment, might cause this study to be detrimental to the subject
7. Pregnant or breast-feeding women
8. Past or current psychiatric illness that would interfere with the subject's ability to comply with protocol requirements or give informed consent.
9. Treatment with any live (attenuated) vaccine within 4 weeks prior to baseline.
10. History of alcohol or drug abuse that would interfere with the subject's ability to comply with protocol requirements.
11. Treatment with any investigational drug within 3 months of screening visit.
D: Inclusion Criteria:

* Clinical diagnosis of ankylosing spondylitis
* Active ankylosing spondylitis

Exclusion Criteria:

* Complete ankylosis of spine
* Previous treatment with etanercept

Answer: C