The Use of Synovial Biopsies in Predicting Response to Biologic Therapy in Rheumatoid Arthritis Patients

Study Overview
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Brief Summary
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SYBRA is an open-label, phase 3, randomized controlled clinical trial that aims to assess the use of synovial biopsies in predicting response to biologic therapy in patients with rheumatoid arthritis that have failed disease-modifying drugs. The project has the potential to help change the current practice by offering the best treatment option. The decision to choose the best treatment for a particular patient is especially important in the context of the growing number of therapies available as a first-line option and the lack of specific biomarkers to predict response to treatment.

Official Title
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The Use of Synovial Biopsies in Predicting Response to Biologic Therapy in Rheumatoid Arthritis Patients

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Anti-TNF
* Drug: JAK inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject should be capable of consent Age 18 and older Classified as rheumatoid arthritis as per EULAR/ACR criteria 2010 Failed one DMARD (Methotrexate, leflunomide, Sulfalsalazine, hydroxychloroquine) Can be on steroid dose <7.5mg Quantiferon negative Hepatitis B, C negative No recent history (<5y) of malignancy Exclusion Criteria: Overlap syndrome Previously treated with a biological medication Heart failure NYHA III/IV Active tuberculosis Active infections Previous history of DVT, PE, or Stroke Other significant comorbidities that will prevent them from taking any biologic medication as per EULAR guidelines on treating rheumatoid arthritis 2020. Pregnancy

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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A (Anti-TNF)<br>Rheumatoid arthritis patients that have failed DMARD therapy will undergo a synovial biopsy under ultrasound guidance and sterile technique. Upon analysis of the sample, patients that are falling into the diffuse myeloid phenotype will be assigned to receive anti-TNF medication at the discretion of the treating physician. | Drug: Anti-TNF<br>* Upon analysis of the sample, patients that are falling into specific phenotypes (diffuse myeloid or pauci-cellular phenotypes) will be assigned to receive anti-TNF as biologic DMARD medications.<br>* Other names: Adalimumab, etanercept, certolizumab, or golimumab;|
| Experimental: Group B (JAK inhibitor)<br>Rheumatoid arthritis patients that have failed DMARD therapy will undergo a synovial biopsy under ultrasound guidance and sterile technique. Upon analysis of the sample, patients that are falling into the lymphoid- myeloid phenotype will be assigned to receive JAK inhibitor medication at the discretion of the treating physician. | Drug: JAK inhibitor<br>* Upon analysis of the sample, patients that are falling into specific phenotypes (lymphoid- myeloid or pauci-cellular phenotypes) will be assigned to receive JAK inhibitors as biologic DMARD medications.<br>* Other names: Tofacitinib, baricitinib, or upadacitinib;|
| Experimental: Group C (Anti-TNF or JAK inhibitor)<br>Rheumatoid arthritis patients that have failed DMARD therapy will undergo a synovial biopsy under ultrasound guidance and sterile technique. Upon analysis of the sample, patients that are falling into the pauci-cellular phenotype will be randomized to either anti-TNF or JAK inhibitor medication 1:1. | Drug: Anti-TNF<br>* Upon analysis of the sample, patients that are falling into specific phenotypes (diffuse myeloid or pauci-cellular phenotypes) will be assigned to receive anti-TNF as biologic DMARD medications.<br>* Other names: Adalimumab, etanercept, certolizumab, or golimumab;Drug: JAK inhibitor<br>* Upon analysis of the sample, patients that are falling into specific phenotypes (lymphoid- myeloid or pauci-cellular phenotypes) will be assigned to receive JAK inhibitors as biologic DMARD medications.<br>* Other names: Tofacitinib, baricitinib, or upadacitinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in DAS28 score | Change in DAS28 score indicating remission compared to baseline in at least 50% of patients, where DS28<2.6 indicated remission. * DAS score: disease activity score, where <2.6 indicates remission, 2.6-3.2 low disease activity. 3.2-5.1 moderate disease activity; >5.1 high disease activity; higher values suggest worse outcomes. | Baseline, Visit 3 (12 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HAQ score | Significant decrease in HAQ score compared to baseline. * HAQ (Health assessment questionnaire). Scores vary from 0-to 3. Higher scores are associated with worse outcomes. | Baseline, Visit 3 (12 weeks) | 
| Change in power Doppler activity | Change in power Doppler activity compared to a baseline where no power Doppler activity indicates remission. Measurement in Doppler activity on ultrasound using a grading system developed by EULAR. * Global EULAR-OMERACT Synovitis Score: scores range from 0-3 for each scanned joint. Higher scores correlate with worse outcomes. | Baseline, Visit 3 (12 weeks) | 
| Change in cellular phenotype | Change in cellular phenotype compared to baseline. Estimation of change in the number of inflammatory cells as per the grading criteria. | Baseline, Visit 3 (12 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis, Synovial biopsy, Biologic therapy