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

NCT05379322 — Phase 3, Withdrawn, Abu Dhabi Stem Cells Center

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Registry	NCT05379322, acronym SYBRA
Status	Withdrawn - Decision of the local healthcare authority
Phase	Phase 3
Study type	Interventional; randomized, parallel, masking: none, treatment
Sponsor	Abu Dhabi Stem Cells Center (Other gov)
Conditions	Rheumatoid Arthritis
Interventions	Anti-TNF, JAK inhibitor (Drug)
Dates	start 2023-03-01, primary completion 2023-03-01 (estimated), completion 2023-03-01 (estimated), first posted 2022-05-18, last updated 2025-10-06
Locations	1 site in United Arab Emirates

-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.

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+Arms and interventions

Arm	Type	Interventions	Description
Group A (Anti-TNF)	Experimental	Drug: 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.
Group B (JAK inhibitor)	Experimental	Drug: 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.
Group C (Anti-TNF or JAK inhibitor)	Experimental	Drug: Anti-TNF; Drug: 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.

Anti-TNF (Drug), also known as Adalimumab, etanercept, certolizumab, or golimumab: 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.
JAK inhibitor (Drug), also known as Tofacitinib, baricitinib, or upadacitinib: 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.

+Outcome measures

Primary outcomes

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 outcomes

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

Sex: All, ages: 18 Years to any

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

+Locations (1)

Facility	City	Country	Status
Abu Dhabi Stem Cells Center	Abu Dhabi, Abu Dhabi Emirate	United Arab Emirates

+Investigators

Gianina Statache, MD, Principal investigator, Abu Dhabi Stem Cells Center
Rene A. Rivero Jimenez, PhD, Study chair, Abu Dhabi Stem Cells Center