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NCT Number: NCT02219347

Biomarkers of Remission in Rheumatoid Arthritis (BioRRA)

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.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Newcastle NIHR Clinical Research Facility, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, Tyne & Wear, NE1 4LP, United Kingdom

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

DMARD cessation

Drug

Complete cessation of non-biologic DMARD therapy (single or combination of methotrexate, sulphasalazine and/or hydroxychloroquine)

Primary outcomes

  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 outcomes

  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

Sponsors and collaborators

Lead sponsor

Newcastle-upon-Tyne Hospitals NHS Trust

Other

Collaborators

  • Newcastle University
  • Wellcome Trust

Registry information

Acronym: BioRRA

Important dates

Study start
2014
Primary completion
2017
Study completion
2017
First posted
Aug 18, 2014
Registry last updated
Nov 6, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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