Rheumatoid arthritis Musculoskeletal Diseases Rheumatoid arthritis, unspecified
Conditions
Interventions
In this study, the researchers will recruit patients in remission from RA on traditional disease-modifying therapies (DMARDs), namely methotrexate, sulfasalazine, and/or hydroxychloroquine. These pati
Sponsors
The Newcastle Upon Tyne Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis of rheumatoid arthritis according to the 1987 ACR or 2010 ACR/EULAR classification criteria (applied at any time since diagnosis) 2. Current single or combination use of methotrexate, sulfasalazine and/or hydroxychloroquine. No escalations in dose are permitted in the six months prior to enrolment, although dose reductions in this time are permitted 3. Arthritis currently in remission, as judged clinically by referring healthcare professional 4. Patient and referring clinician willing to consider DMARD withdrawal 5. Age > 16 at time of first diagnosis with RA, and > 18 at time of recruitment
Exclusion criteria
Exclusion criteria: 1. Inability to provide informed consent 2. Current participation or follow-up within another ongoing clinical interventional trial 3. Current pregnancy, or pregnancy planned within next 6 months 4. Major surgery planned within next 6 months (definition of major surgery at discretion of screening clinician) 5. Immunisation within the past 4 weeks 6. Received steroids within past 3 months (oral, parenteral or intra-articular) 7. Use of any DMARD other than methotrexate, sulfasalazine or hydroxychloroquine within the past 6 months (or past 12 months for leflunomide) 8. Increase in the dose of any DMARD in the 6 months prior to screening. 9. Use of biologic therapy within the past 6 months 10. Prior use of cell-depleting biologic therapies 11. Haemoglobin < 9g/L at baseline 12. Contraindication to synovial biopsy – e.g. bleeding diathesis or prolonged use of anticoagulant therapy (warfarin or other direct oral anticoagulants e.g. rivaroxaban) 13. Active crystal arthropathy *Topical, inhaled and intra-nasal steroids are permitted
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of patients who experience a confirmed flare as described in Section 5.9 of the Protocol (DAS28-CRP = 3.2 or DAS28-CRP = 2.4 on two occasions 7-14 days apart) at any time up to/including 24 weeks after cessation of treatment: 1. Disease flare occurrence (proportion at 24 weeks) 2. Time to disease flare (also used to estimate proportion at 24 weeks) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Individual components of the primary outcome of ‘flare’ (DAS28-CRP = 3.2 or DAS28-CRP = 2.4 on two occasions 7-14 days apart) at any time up to/including 24 weeks after cessation of treatment. The individual components are: 1.1. Tender joint count 1.2. Swollen joint count 1.3. Visual analogue scale (patient) 1.4. CRP 2. Immune cell subsets and their activation status. The researchers will be using conventional fluorescence-based flow cytometry and also mass cytometry (CyTOF) to measure the immune cell subsets, specifically the T cells, B cells, dendritic cells and monocytes. This will be done in batches to reduce batch effect and cytometer drift. All of the samples from one patient will be analysed at a single timepoint (following stabilisation and freezing of the samples) 3. Autoantibody profiles. The researchers will transfer serum samples to their industrial partner Orgentec for assessment of antibody specificity. Antigen affinity of key autoantibodies will be measured using BIACORE surface plasmon resonance or similar techniques. Circulating cytokines will be measured in serum and/or plasma using immunoassays or ELISAs 4. Epigenetic profiles: high-order chromatin structures in immune cells, such as PBMC, CD4+ T cells and CD14+ monocytes, will be evaluated on the EpiSwitchTM PCR platform (in partnership with Oxford Biodynamics). Differentiating signatures will be refined using binary EpiswitchTM scores and logistical regression modelling, and the accuracy and robustness of the predictive model determined by ROC analysis. 5. T-cell receptor excision circles as a marker of thymic activity 6. Synovial cell lineages present, including stromal cell subtypes, as well as their associated cytokines and chemokines. Stromal and leukocyte subpopulations will be sorted from synovial biopsy samples by flow cytometry and DNA/RNA/miRNA will be extracted for further downstream transcriptomic analysis. Where possible, key findings will be validated by histology in matched tiss | — |
Countries
England, Scotland, United Kingdom
Contacts
Public ContactKatie Gray
Outcome results
None listed