A MULTICENTER OPEN LABEL STUDY OF ETANERCEPT WITHDRAWAL AND RETREATMENT IN SUBJECTS WITH NON RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS WHO ACHIEVED ADEQUATE 24 WEEK RESPONSE

Period 1:
1. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
2. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Male subjects able to father children and female subjects of childbearing potential and at risk for pregnancy must agree to use a highly effective method of contraception throughout the entire study and
for 28 days after the last study visit:
• Have undergone a documented hysterectomy and/or bilateral oophorectomy;
• Have medically confirmed ovarian failure; or Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle stimulating hormone (FSH) level confirming the post-menopausal state.
4. Duration of symptoms of >=3 months and <5 years at the time of consent.
5. Diagnosis of ax SpA as defined by the ASAS criteria.
The ASAS criteria state that subjects have to have >=3 months of back pain and age of onset <45 years, and:
• Sacroiliitis on imaging plus 1 SpA feature
OR
• Positive Human Leucocyte Antigen B27 (HLA-B27) plus 2 SpA features.
Sacroiliitis on imaging is defined as either:
• Active inflammation on MRI highly suggestive of sacroiliitis associated with SpA
OR
• Defined radiographic sacroiliitis according to the Modified NY criteria.**
**Subjects in this study cannot meet the criteria based on the second bullet (since defined radiographic sacroiliitis is an exclusion criterion).
In order to meet the imaging criteria for ASAS, subjects must have positive sacroiliitis on MRI based on readings performed by the central imaging vendor. This criterion cannot be based on local MRI evaluation or historical MRIs.
If a subject has negative sacroiliitis on MRI, then they must have positive HLA-B27 plus 2 SpA features. Conversely, if a subject is HLAB27 negative, then they must have positive sacroiliitis on MRI and at
least 1 SpA feature.
The SpA features are listed below;
• Inflammatory back pain;
• Arthritis;
• Enthesitis (heel);
• Uveitis;
• Dactylitis;
• Psoriasis;
• Crohn's/ Colitis;
• Good response to NSAIDs;
• Family history of SpA;
• HLA-B27;
• Elevated hsCRP.
6. Subjects must have positive MRI findings (active inflammation on MRI highly suggestive of sacroiliitis associated with SpA) and/or positive hsCRP (defined as hsCRP >3 mg/l).
7. Active symptoms defined by an ASDAS CRP greater than or equal to 2.1 at the screening visit.
8. Back pain with a less than favorable response to current intake of an NSAID at the optimal tolerated dose as determined by the investigator.
Subjects must have experienced less than favorable response to at least 2 NSAIDs (including the current one) taken separately at the optimal tolerated dose with a total combined duration of >4 weeks.
9. Subject must be taking a stable dose of an NSAID for at least 14 days before the first dose.
10. Female or male 18 years or older (20 or older if required by local regulations) but less than 50 at the time of consent.
11. In the opinion of the investigator, subject is reasonable candidate for treatment with ETN.
12. No contraindication to MRI examination (metal implants or inability to lie flat for 30-60 minutes for example).
13. Negative serum pregnancy test performed at screening, negative urine pregnancy test performed prior to the first dose and negative serum pregnancy test collected for analysis prior to the first dose.
14. Ability to self-inject investigational product or have a designee who can do so.
15. Ability to store injectable investigational product under refrigerated conditions.
16. Demonstrated an adequate screening for tuberculosis (TB) in accordance with local country guidelines.
17. Subject is able to complete health outcomes assessments and investigational product diary.
Period 2:
1. Completion of Period 1.
2. Subjects must achieve ASDAS CRP (inactive disease) less than 1.3 at the Week 24 visit in order to be eligible to enter Period 2.
Period 3:
Subjects must meet the criteria for flare in order to be eligible to enter Period 3. Flare is defined as ASDAS ESR greater than or equal to 2.1.

1. Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees directly involved in the conduct of the study.
2. Participation in other studies involving investigational drug(s) (Phases 1-4) within 4 weeks before the current study begins and/or during study participation. Participation in studies involving investigational drug greater than 4 weeks to one year before the current study begins will be permitted on a case-by-case basis.
3. Radiological sacroiliitis Grades 3-4 unilaterally or Grade >=2 bilaterally as defined by the NY criteria. Only results from the central imaging reader will determine eligibility. In all countries except Germany:
Historical x-rays (obtained within 4 months of screening) may be utilized, however these subjects
must exhibit radiological sacroiliitis Grade 0-1 unilaterally or Grade 0 bilaterally.
4. Any previous treatment with a tumor necrosis factor-alpha (TNF-*) inhibitor, B/T cell inhibitor or other biologic or immunosuppressive agent for a condition other than IBD.
5. Subject is currently being treated or had previous treatment within 6 months for IBD with any tumor necrosis factor-alpha (TNF-*) inhibitor or any other immunosuppressant.
6. Evidence of IBD flare within 6 months of first dose.
7. Evidence of active uveitis within 6 months of first dose.
8. Any current or past orthopedic or medical condition that in the opinion of the investigator could cause chronic back pain.
9. Subject has known or suspected allergy, hypersensitivity, or contraindication to ETN, its excipients, or other compounds, related to this class of medication.
10. Subject has concurrent treatment with more than 1 NSAID within 14 days at first dose. Aspirin use, at daily doses up to 325 mg if indicated for cardiovascular protection is permissible and will not be counted as an additional NSAID.
11. Disease modifying anti-rheumatic drugs (DMARDs) other than methotrexate (MTX), sulfasalazine and hydroxychloroquine taken within 4 weeks of first dose. Subjects may be taking only one allowable DMARD at a time.
12. Subject has had an oral dose of prednisone >10 mg/day (or equivalent) or has had a dose change within 4 weeks of first dose.
13. Subject has received an intra-articular, intravenous, intramuscular, or subcutaneous (SC) corticosteroid within 4 weeks of first dose.
14. Subject has current or recent (within 2 years of screening) active TB infection.
• Subjects with remote history (more than 2 years before screening) of active TB are allowed if clear documentation of completion of adequate treatment (as defined by local guidelines) exists.
• Local country guidelines should be observed for appropriate TB screening in the setting of anti-TNF therapy, including a minimum of a chest radiograph and objective TB testing such as a purified protein derivative (PPD) or Quantiferon depending on what is acceptable per local guidelines.
15. Subject has untreated latent TB. (Subjects with known latent TB may be allowed only if local guidelines are followed for therapy and if treatment for latent TB has been adequately completed or initiated at least 4 weeks prior to screening.)
16. Subject has received treatment for latent TB during screening and has had alanine aminotranferase (ALT) and/or aspartate aminotranferase (AST) >=2 times the upper limit of normal (ULN) during this period.
• For subjects that have been diagnosed with latent TB and started treatment during the screening period, additional blood samples for ALT and AST must be drawn between 3-4 weeks after initiating treatment.
The results need to be reviewed prior to first dose.
17. Subjects with a chronic infection, or a serious infection (infection associated with hospitalization and/or intravenous antibiotics) within 4 weeks prior to investigational product administration.
18. Subjects with active infection at the time of the screening visit and or the first dose visit. Certain minor active infections (ie, vaginitis, tinea, etc) could be allowed on a case-by-case basis only after approval from the Pfizer Physician Clinician.
19. Subject has planned elective surgery during the active dosing period (i.e. Period 1).
20. Subject has received any live vaccines (attenuated vaccine) within 4 weeks prior to first dose.
21. Investigational drugs half-lives of greater than 5 weeks taken less than 6 months prior to first dose.
[For the full list of Exclusion Criteria refer to Section 4.4 of the Protocol]