Biomarkers Identification of Anti-tumor Necrosis Factor (TNF) α Agent's Efficacy in Ankylosing Spondylitis Patients

Study Overview
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Brief Summary
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To identify new candidate genes and proteins that are differentially expressed in responders' vs non-responders to anti-TNF alpha therapy at the several time points the investigators will use the transcriptomic and proteomic analyses. Demonstrate a link between gene expression and protein markers regarding prediction to anti-TNF alpha therapy efficacy.

Official Title
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Biomarkers Identification of Anti-TNF α Agent's Efficacy in Ankylosing Spondylitis Patients Using a Transcriptome Analysis and Mass Spectrometry

Conditions
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Ankylosing Spondylitis

Intervention / Treatment
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* Drug: Adalimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: AS according to Portuguese Society of Rheumatology (SPR) guidelines (1984 modified New York Criteria, but allowing the use of MRI as imagiological criteria) Patient enrolment followed national guidelines for TNF antagonist use for the treatment of AS Adults between 18 to 75 years Ability to provide informed consent Corticosteroid therapy allowed (equivalent to ≤ 10 mg prednisone) and / or NSAID(nonsteroidal antiinflammatory drug), stable dose in 4 weeks before study initiation Adequate contraception (barrier or hormonal) in men and women of childbearing age (patients and their partners Adequate renal and hepatic function (2 times ULN) Exclusion Criteria: Current pregnancy or breastfeeding Previous treatment with biologic DMARD's (disease-modifying antirheumatic drug) Intraarticular injections or infiltrations of extraaxial joints and tendons within 28 days before or at screening, or intraarticular injections of sacroiliac joints ≤ 28 days before screening History of rheumatic disorder other than AS Other forms of spondylarthritis than AS Any uncontrolled medical condition (e.g., uncontrolled diabetes mellitus, unstable ischemic heart disease) History or signs of demyelinating disease Malignancy (except for completely treated squamous or basal cell carcinoma) Moderate to severe heart failure (NYHA class III/IV) Positive serology for hepatitis B, hepatitis C, or human immunodeficiency virus Active or latent tuberculosis (TB) or histoplasmosis or other severe infections such as sepsis, and opportunistic infections Infections requiring hospitalization or intravenous treatment with antibiotics within 30 days or oral treatment with antibiotics within 14 days before enrollment Ankylosis of the spine (syndesmophytes presence at all levels from D12 to S1 in X-ray (XR) lateral view) Hypersensitivity to the active substance or to any of the excipients

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adalimumab<br>Adalimumab will be provided to trial participants as 0.8 ml single dose pre-filled syringes containing 40mg adalimumab each. A kit will be dispensed to he subject every two weeks, each kit containing one syringe. | Drug: Adalimumab<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response biomarkers (Assessment of Spondyloarthritis International Society (ASAS) 20 and Ankylosing Spondylitis Disease Activity Score (ASDAS) | To identify anti-TNF alpha clinical response biomarkers by microarrays and proteomics technology. | 14 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| QoL evaluation | To evaluate quality of life using ASQOL and SF-36 questionnaires | 14 weeks | 
| MRI progression | Rachis evaluation according to acute and structural lesions | 14 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ankylosing Spondylitis, adalimumab, TNF-alpha agents, spondyloarthritis, biologic therapies, AS, biomarkers, efficacy prediction