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

Sponsor

Abu Dhabi Stem Cells Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05379322

Collaborator

(none)

145

Enrollment

Location

Arms

Anticipated Duration (Months)

6.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Anti-TNF Drug: JAK inhibitor	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

145 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jul 1, 2022

Anticipated Primary Completion Date :

Oct 1, 2023

Anticipated Study Completion Date :

Apr 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A (Anti-TNF) 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 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. Other Names: Adalimumab, etanercept, certolizumab, or golimumab
Experimental: Group B (JAK inhibitor) 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 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. Other Names: Tofacitinib, baricitinib, or upadacitinib
Experimental: Group C (Anti-TNF or JAK inhibitor) 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 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. Other Names: Adalimumab, etanercept, certolizumab, or golimumab Drug: JAK inhibitor 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. Other Names: Tofacitinib, baricitinib, or upadacitinib

Arm

Intervention/Treatment

Experimental: Group A (Anti-TNF)

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

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.

Other Names:

Adalimumab, etanercept, certolizumab, or golimumab

Experimental: Group B (JAK inhibitor)

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

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.

Other Names:

Tofacitinib, baricitinib, or upadacitinib

Experimental: Group C (Anti-TNF or JAK inhibitor)

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

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.

Other Names:

Adalimumab, etanercept, certolizumab, or golimumab

Drug: JAK inhibitor

Other Names:

Tofacitinib, baricitinib, or upadacitinib

Outcome Measures

Primary Outcome Measures

Change in DAS28 score [Baseline, Visit 3 (12 weeks)]
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.

Secondary Outcome Measures

Change in HAQ score [Baseline, Visit 3 (12 weeks)]
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.
Change in power Doppler activity [Baseline, Visit 3 (12 weeks)]
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.
Change in cellular phenotype [Baseline, Visit 3 (12 weeks)]
Change in cellular phenotype compared to baseline. Estimation of change in the number of inflammatory cells as per the grading criteria.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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