Rheumatoid arthritis Musculoskeletal Diseases Rheumatoid arthritis, unspecified
Conditions
Interventions
1. Rituximab
Rituximab (MabThera® 500mg concentrate for infusion, Roche Products Ltd) is available as 50ml single-use vials containing 500mg Rituximab for infusion (10mg/ml). Patients
Sponsors
Queen Mary University of London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients will be recruited with active RA: 1. 2010 ACR / EULAR Rheumatoid Arthritis classification criteria for a diagnosis of RA 2. DMARD failure eligible for anti-TNF-a therapy as per UK NICE guidelines 3. Minimum of 3 swollen joints – the joint selected for biopsy and a minimum of 2 from 28 joint count set, as assessed at biopsy visit 4. Selected joint for biopsy must be minimum grade 2 synovial thickening, as assessed at the biopsy visit 5. 18 years of age and over 6. Capable of giving informed consent and the consent must be obtained prior to any screening procedures
Exclusion criteria
Exclusion criteria: Patients will be excluded if they have any contraindication to Etanercept, Rituximab or Tocilizumab therapy: 1. Pregnant or breastfeeding 2. Women of child-bearing potential or males whose partners are women of child-bearing potential, unwilling to use an effective method of contraception (recommend double contraception) throughout the trial and beyond the end of trial treatment for the duration as defined in the relevant SmPC; 12 months for Rituximab, at least 3 weeks for Etanercept, and at least 3 months for Tocilizumab. 3. History of or current primary inflammatory joint disease or primary rheumatological autoimmune disease other than RA (if secondary to RA, then the patient is still eligible). 4. Prior exposure to Rituximab, any anti-TNF, Tocilizumab, or any other biologic for treatment of RA 5. Treatment with any investigational agent = 4 weeks prior to baseline or 3 months prior to screening). 21. Known recent substance abuse (drug or alcohol). 22. Poor tolerability of venepuncture or lack of adequate venous access for required blood sampling during the study period 23. Patients unable to tolerate synovial biopsy or in whom this is contraindicated including patients on anticoagulants. Oral antiplatelet agents are permitted. 24. Currently recruited to another clinical trial. 25. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Treatment response will be assessed using the ACR20 response at 16 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. For the B-cell rich synovial pathotypes, we aim to compare treatment effects (with 95% confidence intervals) of Rituximab to Tocilizumab and Etanercept (treated together for analysis). 2. The interaction between treatments and B-cell status (rich and poor) will be tested using the likelihood ratio test between nested logistic regression models. The model will use all the sample and will be adjusted for MTX. 3. Patients who fail to respond during the first 16 weeks and cross-over treatment will also provide evidence regarding the efficacy of the two treatments and the predictive significance of B-cells in synovial biopsies. The post cross-over results will be combined with the pre-cross-over results in a secondary analysis stratified by pre/post cross-over. | — |
Countries
Belgium, Italy, Portugal, Spain
Contacts
Public ContactJo Peel
Outcome results
None listed