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

Official 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.

Eligibility Requirements

• Minimum Age: 18 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE

Study Arms

• Group A (Anti-TNF) (EXPERIMENTAL)
  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)
  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)
  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.

Interventions

• 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.
• 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.

Primary Outcomes

• Change in DAS28 score (Baseline, Visit 3 (12 weeks))

Secondary Outcomes

• Change in HAQ score (Baseline, Visit 3 (12 weeks))
• Change in power Doppler activity (Baseline, Visit 3 (12 weeks))
• Change in cellular phenotype (Baseline, Visit 3 (12 weeks))

Eligibility Criteria

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

Trial Locations

• Abu Dhabi Stem Cells Center, Abu Dhabi, Abu Dhabi Emirate, United Arab Emirates

Study Officials

• Gianina Statache, MD — PRINCIPAL_INVESTIGATOR
  Abu Dhabi Stem Cells Center
• Rene A. Rivero Jimenez, PhD — STUDY_CHAIR
  Abu Dhabi Stem Cells Center

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