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| Name | Class |
|---|---|
| Newcastle University | OTHER |
| Wellcome Trust | OTHER |
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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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DMARD cessation | Other | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DMARD cessation | Drug | Complete cessation of non-biologic DMARD therapy (single or combination of methotrexate, sulphasalazine and/or hydroxychloroquine) |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| John D Isaacs, PhD MBBS | Newcastle University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Newcastle NIHR Clinical Research Facility, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust | Newcastle upon Tyne | Tyne & Wear | NE1 4LP | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38316770 | Derived | Baker KF, McDonald D, Hulme G, Hussain R, Coxhead J, Swan D, Schulz AR, Mei HE, MacDonald L, Pratt AG, Filby A, Anderson AE, Isaacs JD. Single-cell insights into immune dysregulation in rheumatoid arthritis flare versus drug-free remission. Nat Commun. 2024 Feb 5;15(1):1063. doi: 10.1038/s41467-024-45213-2. |
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| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
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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 |
| D003240 |
| Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |