Biomarkers of Remission in Rheumatoid Arthritis (BioRRA) (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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: DMARD cessation

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Tyne & Wear
    • Newcastle upon Tyne, Tyne & Wear, United Kingdom, NE1 4LP
      • Newcastle NIHR Clinical Research Facility, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-to-flare of arthritis activity following DMARD cessation	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	From recruitment, assessed up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical biomarkers predictive of DMARD-free remission	Baseline clinical factors predictive of time-to-flare of arthritis activity following DMARD cessation.	At recruitment
Ultrasound biomarkers of DMARD-free remission	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.	At recruitment
Genetic biomarkers of DMARD-free remission	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.	At recruitment
Cytokine biomarkers of DMARD-free remission	Baseline signature of differential cytokine levels in peripheral blood predictive of time-to-flare of arthritis activity, as measured using a multiplex cytokine assay.	At recruitment
Rheumatoid arthritis disease activity	Measured by Disease Activity Score in 28 joints (DAS28-CRP) score.	At recruitment and at 1 month, 3 months and 6 months following DMARD cessation
Physical disability	Measured by Health Assessment Questionnaire Disability Index (HAQ-DI) questionnaire	At baseline and at 6 months following DMARD cessation

Collaborators and Investigators

• Sponsor: Newcastle-upon-Tyne Hospitals NHS Trust
• Collaborators: Wellcome Trust; Newcastle University
• Investigators: Principal Investigator: John D Isaacs, PhD MBBS, Newcastle University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2014
• Primary Completion (Actual): August 1, 2017
• Study Completion (Actual): August 1, 2017

Study Registration Dates

• First Submitted: August 15, 2014
• First Submitted That Met QC Criteria: August 15, 2014
• First Posted (Estimate): August 18, 2014

Study Record Updates

• Last Update Posted (Actual): November 6, 2017
• Last Update Submitted That Met QC Criteria: November 1, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: rheumatoid arthritis; remission; ultrasonography; biological markers; T cell; microarray; survival analysis
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: NUTH7100

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO