Rheumatoid arthritis (RA) Musculoskeletal Diseases
Conditions
Interventions
Patients will be recruited who are starting a new drug treatment within one of the following drug classes as part of routine care: TNF-inhibitor, IL6R-inhibitor, or JAK-inhibitor. Following a minimall
Sponsors
Queen Mary University of London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 24/06/2025: 1. Adults (aged 18 years and over) with a diagnosis of rheumatoid arthritis (2010 ACR/EULAR criteria) 2. Failure of TNF inhibitor, either as monotherapy or in combination with csDMARDs, switching to a different TNFi, an IL6Ri or a JAKi 3. Eligible to start a TNFi, IL6Ri, or JAKi, according to local pathways/guidelines 4. Patients on any other additional csDMARDs at the time of starting their biologic should be on a stable dose in the 4 weeks prior to the baseline visit 5. At least one swollen joint amenable to synovial biopsy (minimum grade 2 synovial thickening, as assessed at the biopsy visit) 6. Minimum three swollen joints (including the joint selected for biopsy) and a minimum DAS28 (ESR) score of 3.2 at screening 7. Patient is judged by the supervising clinician to be a suitable candidate based upon medical history, physical examination, vital signs, and routine laboratory tests 8. Willing and capable of giving informed consent, which must be obtained prior to any study-specific screening procedures 9. Willing and able to comply with scheduled visits, laboratory tests, and other study procedures Previous inclusion criteria: 1. Adults (aged 18 years and over) with a diagnosis of rheumatoid arthritis (2010 ACR/EULAR criteria) 2. Primary failure of first-line TNF inhibitor, either as monotherapy or in combination with csDMARDs, switching to a different TNFi, an IL6Ri or a JAKi 3. Eligible to start a TNFi, IL6Ri, or JAKi, according to local pathways/guidelines 4. Patients must be receiving methotrexate therapy and be on a stable dose for a minimum of 4 weeks prior to entry into the trial 5. Patients on any other additional csDMARDs at the time of starting their biologic should be on a stable dose in the 4 weeks prior to the baseline visit 6. At least one swollen joint amenable to synovial biopsy (minimum grade 2 synovial thickening, as assessed at the biopsy visit) 7. Minimum three swollen joints (including the joint selected for biopsy) and a minimum DAS28 (ESR) score of 3.2 at screening 8. Patient is judged by the supervising clinician to be a suitable candidate based upon medical history, physical examination, vital signs, and routine laboratory tests 9. Willing and capable of giving informed consent, which must be obtained prior to any study-specific screening procedures 10. Willing and able to comply with scheduled visits, laboratory tests, and other study procedures
Exclusion criteria
Exclusion criteria: 1. Patients unable to tolerate synovial biopsy or in whom this is contraindicated including patients on anti-coagulants (e.g. warfarin), or in whom this is contraindicated at physician’s discretion (e.g. patients with bleeding disorders, or patients with liver disease). Patients on short-acting direct oral anticoagulant agents can be considered when the anti-coagulant can be temporarily stopped, in line with local guidelines for procedures with a low risk of bleeding, taking into account the individual thromboembolic risk. Oral antiplatelet agents are permitted. 2. Patients in whom there is no suitable joint for biopsy 3. Patients who are stopping their previously prescribed TNF inhibitor due to toxicity/side effects, rather than failure to respond. 4. Intra-articular or parenteral corticosteroids =4 weeks prior to the biopsy/baseline visit. 5. Oral prednisolone more than 10 mg/d or equivalent =4 weeks prior to the biopsy/baseline visit. If patients are taking oral corticosteroids during this period, they must be on a stable dose (i.e. they must not start or change the dose during this period). 6. Patients with a serious underlying medical disorder (e.g. end-stage renal disease) 7. Poor tolerability of venepuncture or lack of adequate venous access for required blood sampling during the study period 8. Active infection or any other contraindications to start TNFi, IL6Ri, or JAKi, as per local/international guidelines and SmPc (including specific risk assessment for CV events, venous thromboembolism (VTE), cancer, and infections for JAKi) 9. Individuals who are unable to give informed consent for any reason (vulnerable groups)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Rheumatoid arthritis disease activity measured in the Clinical Disease Activity Index at 16 weeks from baseline at week 0 in each medication group (Tumor Necrosis Factor, Interleukin 6, & Janus kinase inhibitors) and within the whole population | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. The percentage of patients with ultrasound-defined remission (ST/PD1) at 16 weeks 2. The percentage of patients with Disease Activity Score-28 for Rheumatoid Arthritis with ESR (DAS28-ESR) below 3.2 at 16 weeks 3. The percentage of patients with a Clinical Disease Activity Index between 2.8 and 10 (Low Disease Activity) at 16 weeks 4. The percentage of patients with a Clinical Disease Activity Index below 2.8 (in remission) at 16 weeks 5. Disability, pain, medication effects, costs of care, and mortality measured using the Health Assessment Questionnaire (HAQ-DI) at 16 weeks from baseline at week 0 6. Health status of particular populations measured using the Short Form Health Survey (SF-36) at 16 weeks from baseline at week 0 | — |
Countries
Austria, England, Italy, Netherlands, Norway, Sweden, United Kingdom
Contacts
Public ContactAlessia Baseggio Conrado
Outcome results
None listed