Can we identify predictors of treatment responses to biologic therapies in patients with rheumatoid arthritis?

Not Applicable

Completed

• Conditions: Rheumatoid arthritis; Rheumatoid arthritis, unspecified; Musculoskeletal Diseases

• Registration Number: ISRCTN43336433
• Lead Sponsor: Queen Mary University of London

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-05-17
• Study Completion: 2021-01-09
• Last Update Posted: 22 August 2022

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 226

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

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 < 5 half-lives of the investigational drug (whichever is the longer)
6. Intra-articular or parenteral corticosteroids = 4 weeks prior to the screening visit.
7. Oral prednisolone more than 10mg/d or equivalent = 4 weeks prior to baseline synovial biopsy.
8. Active infection
9. Known HIV, active Hepatitis B/C infection. Hepatitis B screening test must be performed at or in the preceding 3 months of the screening visit.
10. Septic arthritis of a native joint within the last 12 months
11. Septic arthritis of a prosthetic joint within 12 months or indefinitely if the joint remains in situ
12. Latent TB infection unless they have completed adequate antibiotic prophylaxis
13. Malignancy (other than basal cell carcinoma) within the last 10 years
14. New York Heart Association (NYHA) grade III or IV congestive heart failure
15. Demyelinating disease
16. Known allergy to latex, Rituximab, Tocilizumab or Etanercept
17. Any other contra-indication to the study medications as detailed in the applicable SmPC including low IgG levels, at physician’s discretion
18. Receipt of live vaccine <4 weeks prior to first IMP infusion or dose
19. Major surgery in 3 months prior to first IMP infusion or dose
20. Presence of a transplanted organ (with the exception of a corneal transplant >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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Treatment response will be assessed using the ACR20 response at 16 weeks

Secondary Outcome Measures

Name	Time	Method
<br> 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).<br> 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.<br> 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.<br>