Identification of New Biomarkers to Promote Personalized Treatment of Patients With Inflammatory Rheumatic Diseases

Study Overview
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Brief Summary
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Introduction: The medical treatment of inflammatory rheumatic diseases has improved dramatically during the last decades primarily due to the introduction of biological disease modifying anti-rheumatic drugs (bDMARDs). However, bDMARD treatment failure occurs in 30-40% of patients due to lack of effectiveness or side effects. The tools to predict treatment outcomes in the individual patient are currently limited. The objective of the present study is to identify diagnostic, prognostic and predictive biomarkers, which can be used to 1) diagnose inflammatory rheumatic diseases early in the disease course with high specificity and sensitivity, 2) improve prognostication or 3) predict treatment effectiveness and tolerability for the individual patient. Methods and analysis: Observational and translational open cohort study with prospective collection of clinical data and biological materials in patients with inflammatory rheumatic diseases treated in routine care. Patients contribute one cross-sectional blood sample (i.e. whole blood, serum, EDTA-plasma and -buffy coat, and blood in PAXgene RNA tubes) and/or are enrolled for longitudinal follow-up upon start of new DMARD (blood sampling after 0/3/6/12/24/36/48/60 months' treatment). Demographics, disease characteristics, comorbidities and lifestyle factors are registered at inclusion; DMARD treatment and outcomes are collected repeatedly during follow-up. Currently (June 2017) >5,000 samples from ≈3,000 patients have been collected. Data will be analysed using appropriate statistical analyses. Ethics and dissemination: The protocol is approved by the Danish Ethics Committee and The Danish Data Protection Agency. All participants give written informed consent. Biomarkers will be evaluated and published according to REMARK, STROBE and STARD guidelines. Results will be published in peer-reviewed medical journals and presented at international conferences.

Official Title
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Identification of New Biomarkers to Improve Diagnostics or Predict Treatment Responses, Adverse Events or Prognosis in Patients With Inflammatory Rheumatic Disease Followed in the Danish Nationwide Quality Registry, DANBIO

Conditions
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Arthritis, Rheumatoid, Psoriatic Arthritis, Axial Spondyloarthritis, Connective Tissue Diseases, Gout

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with or suspected for the following diseases: rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (axSpA) or other inflammatory rheumatic diseases, connective tissue disorders or gout Aged 18 year or older Able to give informed consent Exclusion Criteria: None

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 |
| --- | --- |
| Cross-sectional samples:<br>Any patient followed in the DANBIO registry may be invited to participate when they meet for a scheduled routine clinical visit. These patients provide one cross-sectional blood sample. | |
| Longitudinal samples:<br>Any patient followed in the DANBIO registry will be invited to participate when they start treatment with a new DMARD. Switching from csDMARD to bDMARD, or from one bDMARD to another bDMARD indicates a new baseline. | |
| Samples of other biological material:<br>Patients followed in the DANBIO registry may be invited to participate if scheduled for one of the following procedures: joint puncture with extraction of synovial fluid, surgery or tissue sampling involving synovia, cartilage, bone, bone-marrow or other tissues. Representative samples from the synovial fluid or relevant tissue are collected after routine diagnostic or therapeutic analyses have been done | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To diagnose inflammatory rheumatic diseases early in the disease course with high specificity and sensitivity | Number of patients suspected of rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, gout or connective tissue diseases that can be correctly diagnosed | Changes from baseline to 3, 6, 12, 24, 36, 48, and 60 months | 
| To improve prognostication | Number of patients that can be correctly prognosticated by progression in physical function (by HAQ) and in bone damage (by imaging) | At diagnosis and after 3, 6, 12, 24, 36, 48 and 60 months | 
| To predict treatment effectiveness and tolerability for the individual patient | Number of patients that achieve a standardized treatment response and do not experience serious adverse events | At treatment onset and at 3, 6, 12, 24, 36, 48 and 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inflammatory rheumatic diseases, Biomarkers, Tailored treatment, Personalised medicine, DANBIO, Danish Rheumatologic Biobank, clinical data