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Biomarkers of Remission in Rheumatoid Arthritis (BioRRA) (BioRRA)

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ClinicalTrials.gov Identifier: NCT02219347
Recruitment Status : Completed
First Posted : August 18, 2014
Last Update Posted : November 6, 2017
Sponsor:
Collaborators:
Newcastle University
Wellcome Trust
Information provided by (Responsible Party):
Newcastle-upon-Tyne Hospitals NHS Trust

Brief Summary:

Rheumatoid arthritis is a common condition affecting approximately 1% of the United Kingdom population; it is an autoimmune disease where the body's natural defences (the immune system) attack the body itself resulting, most notably, in joint damage and arthritis. To help prevent this, patients with rheumatoid arthritis need to take disease-modifying anti-rheumatic drugs (DMARDs). As rheumatoid arthritis is a life-long condition, these drug treatments are prescribed as long-term medications taken for many years.

With successful drug treatment, many patients are able to achieve an excellent control of their disease and their arthritis can go in to remission. At present, there are no markers which can reliably predict which of these patients can reduce their drug treatment, and hence benefit from a lower risk of side effects and inconvenience, without an increase in their arthritis activity.

We invite patients with stable rheumatoid arthritis to participate in this study conducted by Newcastle upon Tyne Hospitals NHS Foundation Trust in collaboration with Newcastle University and funded by the Wellcome Trust. Patients whose arthritis is confirmed as being in remission will be able to stop their DMARD medication and be monitored for a period of 6 months. Patients whose arthritis activity increases during this time will be able to restart their DMARD medication, whereas those patients whose arthritis remains in remission will be able to stay off DMARD medication.

The main aim of this study is to identify clinical, ultrasound and blood markers that can predict which patients will remain in remission after stopping DMARD medication. If identified, these markers could be a useful guide to doctors and patients in the future when deciding whether to stop DMARD therapy.


Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: DMARD cessation Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 74 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Biomarkers of Remission in Rheumatoid Arthritis (BioRRA)
Actual Study Start Date : August 2014
Actual Primary Completion Date : August 2017
Actual Study Completion Date : August 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
DMARD cessation
All patients recruited to the study who have a Disease Activity in 28 Joints C-Reactive Protein (DAS28-CRP) score of < 2.4 and who do not have power Doppler synovitis on a 7-joint musculoskeletal ultrasound scan will stop their DMARD therapy. These patients will then be followed-up for a period of 6 months or until flare of their arthritis activity, whichever is sooner.
Drug: DMARD cessation
Complete cessation of non-biologic DMARD therapy (single or combination of methotrexate, sulphasalazine and/or hydroxychloroquine)




Primary Outcome Measures :
  1. Time-to-flare of arthritis activity following DMARD cessation [ Time Frame: From recruitment, assessed up to 6 months ]
    Flare of arthritis activity defined as Disease Activity Score in 28 Joints C-Reactive Protein (DAS28-CRP) score greater than or equal to 2.4


Secondary Outcome Measures :
  1. Clinical biomarkers predictive of DMARD-free remission [ Time Frame: At recruitment ]
    Baseline clinical factors predictive of time-to-flare of arthritis activity following DMARD cessation.

  2. Ultrasound biomarkers of DMARD-free remission [ Time Frame: At recruitment ]
    Baseline musculoskeletal ultrasound biomarkers predictive of time-to-flare of arthritis activity following DMARD cessation, including presence or absence of greyscale synovitis/tenosynovitis and erosions.

  3. Genetic biomarkers of DMARD-free remission [ Time Frame: At recruitment ]
    Baseline signature of differential gene expression in peripheral CD4+ T cells predictive of DMARD-free remission at 6 months following DMARD cessation, as measured using RNA sequencing.

  4. Cytokine biomarkers of DMARD-free remission [ Time Frame: At recruitment ]
    Baseline signature of differential cytokine levels in peripheral blood predictive of time-to-flare of arthritis activity, as measured using a multiplex cytokine assay.

  5. Rheumatoid arthritis disease activity [ Time Frame: At recruitment and at 1 month, 3 months and 6 months following DMARD cessation ]
    Measured by Disease Activity Score in 28 joints (DAS28-CRP) score.

  6. Physical disability [ Time Frame: At baseline and at 6 months following DMARD cessation ]
    Measured by Health Assessment Questionnaire Disability Index (HAQ-DI) questionnaire



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Clinical diagnosis of rheumatoid arthritis made by consultant rheumatologist at least 12 months previously
  • Current single or combination use of methotrexate, sulphasalazine and/or hydroxychloroquine
  • Arthritis currently in remission, as judged clinically by referring healthcare professional
  • Willing to consider DMARD withdrawal

Exclusion Criteria:

  • Use of biologic therapy within the past 6 months
  • Received steroids within past 3 months (enteral, parenteral or intra-articular)
  • Use of any DMARD other than methotrexate, sulphasalazine or hydroxychloroquine within the past 6 months (or past 12 months for leflunomide)
  • Current pregnancy, or pregnancy planned within next 6 months
  • Current participation within another clinical trial
  • Inability to provide informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02219347


Locations
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United Kingdom
Newcastle NIHR Clinical Research Facility, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust
Newcastle upon Tyne, Tyne & Wear, United Kingdom, NE1 4LP
Sponsors and Collaborators
Newcastle-upon-Tyne Hospitals NHS Trust
Newcastle University
Wellcome Trust
Investigators
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Principal Investigator: John D Isaacs, PhD MBBS Newcastle University

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Responsible Party: Newcastle-upon-Tyne Hospitals NHS Trust
ClinicalTrials.gov Identifier: NCT02219347     History of Changes
Other Study ID Numbers: NUTH7100
First Posted: August 18, 2014    Key Record Dates
Last Update Posted: November 6, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Newcastle-upon-Tyne Hospitals NHS Trust:
rheumatoid arthritis
biological markers
remission
ultrasonography
microarray
survival analysis
T cell
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antirheumatic Agents