Sustained drug-free remission (SDFR) is achievable in up to 50% of patients with rheumatoid arthritis (RA) in drug-induced remission. However, methods to predict SDFR, its immunological basis, and its impact from a patient perspective remain unknown. The goal of this proposal is to address these unmet needs in three distinct yet complementary work packages (WPs). In WP1, we aim to validate our prototype cytokine biomarker of SDFR using our existing sample biobanks. In WP2, we aim to explore and understand specific mechanisms that potentiate SDFR as implicated by our pilot data, namely: the abundance, phenotype and function of CD4+ regulatory T cells (Tregs) and ACPA-expressing B cell subsets; and markers of regulatory macrophage and intestinal barrier function. In WP3, we aim to understand the impact of living with SDFR from a patient perspective using qualitative methodology. If successful, our project will support a future clinical efficacy trial of biomarker-driven drug cessation in RA remission, a paradigm shift in the management of RA. Furthermore, new insights into the immunobiology of SDFR could identify novel approaches to treat and prevent RA flare, and understanding the lived experience of SDFR will help to guide patient-clinician discussions around drug cessation.
WP1 – Cross-validation of biomarkers of SDFR.
WP2 – Longitudinal molecular and cellular characterisation of SDFR.
WP3 – Understanding the lived experience of SDFR from a patient perspective.
1. Clinical review and blood sample donation from SDFR patients from our clinical cohorts (completion April 2025)
2. Cytokine biomarker validation (completion April 2024)
3. Treg suppression assays (completion August 2025)
4. B cell flow cytometry assays (completion August 2025)
5. Macrophage and intestinal barrier marker assays (completion August 2025)
6. Qualitative patient interviews (completion April 2025)
7. Manuscript preparation and dissemination (completion Jan 2026)
Patient research partners form an integral component of this project, and cut across all proposed activities. Our patient research partners will:
1. Be members of the Project Steering Group
2. Be involved in the preparation of documents for ethical approvals, including writing and editing patient information sheets
3. Help to develop WP3 topic guides and analyse qualitative data, checking the validity of themes identified
4. Help in the dissemination of the results of our study, from being named authors on publications through to oral and written presentations to lay audiences.