Evaluation Effects of Treatment With IL-6R Inhibitor on Clinical Response and Biomarkers in Patients With Rheumatoid Arthritis (RA) Not Responding to DMARDs and/or a First Biological Agent.

Study Overview
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Brief Summary
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The purpose of this study is to assess the clinical response to IL-6 inhibition defined as Low Disease Activity (DAS44) <2.4) at the follow-up visit at 12 months and the correlation between the biomarkers and treatment response.

Official Title
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Evaluation Effects of Treatment With IL-6R Inhibitor on Clinical Response and Biomarkers in Patients With Rheumatoid Arthritis (RA) Not Responding to DMARDs and/or a First Biological Agent.

Conditions
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Rheumatoid Arthritis (RA)

Intervention / Treatment
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* Other: Biomarkers Measures


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Signed informed consent form; Patients aged 18 - 75 years; RA classified in compliance with the 2010 ACR/EULAR criteria; Patients that have to suspend a previous treatment with DMARDs for total ineffectiveness or intolerance to drugs and/or patients that have not responded adequately to first-line combination DMARDs / biological treatment; Patients for which is indicated to start a treatment with an inhibitor of IL-6R for high values indicative of systemic inflammation (ESR>=28 mm/hour, PCR>5 mg/l , Fibrinogen >400 mg/dl and or Albumin <3.5 g/dl) and high disease activity (DAS>2.4), or contraindications to DMARDs use which make it necessary to take biological drug in monotherapy. Corticosteroids therapy stable (< = 7.5 mg)for at least four weeks; Joint symptoms for at least three but no more than 24 months from the screening visit; DAS44 >2.4 and/or SDAI >11 Willing and able to comply with study procedures and timing. Exclusion criteria: On going pregnancy or lactation; Severe active infections; Patients with other clinically significant concomitant diseases whose treatment or outcome could interfere with the expected evaluations of the study protocol. Blood AST or ALT levels >5 times the upper normal limit; ANC count <0.5 x 109/L Platelet count <50 x103 /μL Patients with other autoimmune rheumatic diseases, in addition to AR (for example systemic lupus erythematosus [SLE], scleroderma, polymyositis, ecc…) Medical history or concomitant joint diseases in additions to AR (for example tophaceous gout, reactive arthritis, psoriatic arthritis).

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 |
| --- | --- |
| Other: Tocilizumab<br>Biomarkers Measures At the routine visits (0, 3, 6, 12 and 18 months), a clinical evaluation will be made and samples collected for assaying the biomarkers. | Other: Biomarkers Measures<br>* At the routine visits (0, 3, 6, 12 and 18 months), a clinical evaluation will be made and samples collected for assaying the biomarkers.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Activity Score (DAS-44) |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Simplified Disease Activity Index (SDAI);Biomarkers Measures |  | SDAI at 3-6-12-18 months | 
| Biomarkers Measures | Evaluation by ELISA of the levels of the following biomarkers: IL-8, MCP-1, Chemerin, IL-1α, IL-1β, IL-17, IL-23, TGFβ1, IL-10, BAFF.in the plasma: | Biomarkers Measures at 3-6-12-18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis, Early RA, RA, IL-6, IL-6R, Inhibitor, Inhibition, Tocilizumab, Biomarkers, DMARDs, Biological, DAS, SDAI, AR/BIOM, OEG