A single-site study to understand the best route of delivery for a new cell-based treatment created from patient's own white blood cells for rheumatoid arthritis

INTERVENTION: Participants will be randomly allocated by a computer (Sealed Envelope) to one of five groups. One group will receive the current usual treatment for RA, and the other four groups will receive a single dose of TolDCcitpep in addition to the current usual treatment. Of the four treatment groups, one will receive a dose of 10^7 TolDCcitpep via intra‐dermal injection to the upper thigh, one will receive a dose of 10^7 TolDCcitpep via intra‐articular injection to the knee, one will receive a dose of 10^5 TolDCcitpep via intra‐nodal injection into an inguinal lymph node and one will receive a dose of 10^7 TolDCcitpep via intra‐nodal injection into an inguinal lymph node. TolDCcitpep is manufactured from the participant’s white blood cells, and collected via leukapheresis one week before treatment. All participants will be closely monitored over 12 weeks. CONDITION: Rheumatoid arthritis ; Musculoskeletal Diseases PRIMARY OUTCOME: Signs of immunomodulation will be measured from fresh blood, cryopreserved PBMC samples and lymph node aspirate samples. As there is currently no agreed biomarker for tolerance induction, we will use a range of modalities to identify levels of cell types and cell markers. Blood samples will be collected at baseline, 1, 3, and 6 weeks. Lymph node aspirate will be collected at baseline and 1 week. SECONDARY OUTCOME: 1. Efficacy is measured using changes in American College of Rheumatology (ACR) criteria of a 20% improvement in the core set measures for a patient to reach improvement (ACR20), ACR50, ACR70 and Disease Activity Score (DAS‐28) scores from baseline to weeks 1, 3, 6, and 12; 2. Safety is measured using the reporting of adverse events and serious adverse events at baseline, 1, 3, 6, and 12 weeks; 3. Patient acceptability is measured using a 1‐5 Likert scale questionnaire at 12 weeks INCLUSION CRITERIA: 1. Adults aged 18 years old or over 2. Rheumatoid Arthritis fulfilling 1987 ARA criteria or 2010 ACR/EULAR Classification Criteria 3. ACPA positive (>3 Xupper limit of normal) 4. Able and willing to give informed consent and comply with the study protocol 5. Disease duration at least 4 months and less than ten years 6. ACR Functional Class I‐III 7. DAS 28 <5.1 8. If receiving disease‐modifying anti‐rheumatic drugs (DMARD) these can be at any dose or combination of methotrexate, sulphasalazine, azathioprine, hydroxychloroquine, abatacept, rituximab (last dose >6 months ago), TNF‐alpha inhibitors and IL6 receptor antagonists but must have been stable for 4 weeks. 9. Stable dose of non‐steroidal anti‐inflammatory drugs (NSAID) for at least 4 weeks prior to screening (only applicable for patients taking NSAID as part of their standard care) 10. Possess at least one copy of a shared epitope HLA DRB1 allele (0101; 0102; 0105; 0401; 0404; 040