Assess Structural Damage in Rheumatoid Arthritis Using Biomarkers and Radiography

Study Overview
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Brief Summary
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Recruited patients will include those about to begin Disease-Modifying Antirheumatic Drug) DMARD therapy or about to change DMARD therapy. Disease activity will be monitored systematically every 3 months by the Disease Activity Score. Changes in standard DMARD and/or anti-Tumor Necrosis Factor α (anti-TNFα) therapy will be made according to specific recommendations for patients receiving these therapies. Biomarker samples will be collected every 3 months and prior to change in DMARD and/or anti-TNF therapy as defined below. A blood sample (40 ml) for serum will be taken for biomarker studies and processed according to the international committee of Outcome Measures in Rheumatology (OMERACT) recommendations for the minimal handling of biomarker samples. A urine sample (20 ml) will also be taken and processed as for serum. Radiography (X-rays) will be conducted every 6 months (baseline, 6, 12, 18, 24 months). Patients will be followed for 2 years.

Detailed Description
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Treatment is Disease Activity Score (DAS) driven. Changes in standard DMARD and/or anti-TNFα therapy will be implemented according to 2010 European League against Rheumatism (EULAR) recommendations which state a target of remission (DAS44 <1.6) for patients receiving standard DMARD therapy in the setting of early disease and a target of low disease activity state (LDAS) (DAS44 ≤2.4) for patients receiving anti-TNFα therapy in the setting of established disease.

Official Title
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Prospective Validation of Soluble Biomarkers as Predictors of Structural Damage in Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Other: Observational study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (selected): 18 years of age or older RA according to the 2010 Rheumatoid Arthritis Classification Criteria Joint symptoms for ≥ 3 months prior to screening DAS44 > 2.4 About to start DMARD therapy (methotrexate, salazopyrin, hydroxychloroquine, chloroquine, leflunomide) or increased dose of methotrexate by ≥10 mg weekly to a maximum dose of 25mg weekly (if already receiving >15mg will require add-on DMARD/anti-TNF or switch to alternative DMARD), add-on of alternative DMARD, switch to alternative DMARD, start of first anti-TNFα agent (adalimumab, etanercept, infliximab, certolizumab pegol, golimumab) If already on DMARD therapy this has been stable for the 3 months prior to the baseline visit If already on systemic steroid, dose must be stable (prednisone ≤ 7.5mg/day) for 1 month prior to the baseline visit Patient will be available for follow up for a minimum of 24 months from the baseline visit Exclusion Criteria (selected): Intra-articular steroid injection within 4 weeks prior to the baseline visit Prior treatment with anti-TNFα or other biological agent (rituximab, abatacept, tocilizumab) Malignancy within past 5 years (other than basal cell carcinoma that has been adequately treated or excised, squamous cell cancer of the skin, and cervical carcinoma in situ) History of: Serious infection (defined as requiring parenteral antibiotics or hospitalization) within 3 months prior to the baseline visit; Active tuberculosis or history of tuberculosis without documented curative treatment and/or positive tuberculin reaction to PPD (Purified Protein Derivative) For patients starting anti-TNF therapy, a positive TB screening test and no record of effective prophylaxis according to local expert recommendations Known infection with Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Rheumatoid Arthritis<br> | Other: Observational study<br>* RA patients on standard DMARD therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the independent predictive validity of several soluble biomarkers for predicting structural damage in Rheumatoid Arthritis (RA). |  | 24 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To establish which modifiable clinical and laboratory predictors used in routine practice individually and in combination, have the strongest and the most consistent association with change in radiographic damage in patients on standard RA therapy. |  | 24 Months |