Topic: Musculoskeletal disorders
Conditions
Interventions
50 RA patients requiring anti-TNFa therapy after failure of conventional Disease Modifying Anti Rheumatic Drugs, e.g. methotrexate, according to NICE guidelines, will be recruited to the study followi
Sponsors
Queen Mary University of London (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men and women = 18 and = 65 years of age, with RA as defined by the 2010 revised EULAR/ACR classification criteria 2. An RA diagnosis as defined by the 2010 revised EULAR/ACR classification criteria 3. Subjects who fulfill the NICE guidelines for biologic therapy as their first-line treatment following failure of standard disease modifying anti-rheumatic therapy 4. Subjects may be on cDMARDs of which one must be MTX, or on MTX monotherapy, but should be receiving it for at least 2 months, with a stable dose of 7.525 mg/week for a minimum of 4 weeks 5. Subjects may be on oral steroids (prednisone =10 mg/day, or equivalent corticosteroid) with a stable dose for the 4 weeks prior to Visit 0 6. Men and women of childbearing potential must use adequate birth control measures (e.g. abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) for the duration of the study 7. Patient must be able to adhere to the study visit schedule 8. The patient must be capable of giving informed consent and the consent must be obtained prior to any screening procedures 9. Must have a chest X-ray within 3 months prior to commencement of anti-TNF therapy with no evidence of malignancy, infection or fibrosis Target Gender: Male & Female; Upper Age Limit 65 years ; Lower Age Limit 18 years
Exclusion criteria
Exclusion criteria: 1. Women who are pregnant or breastfeeding 2. Previous use of rheumatoid arthritis anti-TNF biologics, or ANY other type of biologic therapy or investigational medicinal product 3. Treatment with any other therapeutic agent targeted at reducing TNF within 3 months of screening 4. Serious infections (such as, HIV, HBV, pneumonia or pyelonephritis) in the previous 3 months. Less serious infections (such as acute upper respiratory tract infection [colds] or simple urinary tract infection) need not be considered exclusions at the discretion of the investigator 5. Have active TB or have evidence of latent TB (old or latent TB on chest x-ray,without adequate therapy for TB initiated prior to first dose of study drug). Also excluded are patients with evidence of an old or latent TB infection without documented adequate therapy. Patients with a current close contact with an individual with active TB and patients who have completed treatment for active TB within the previous 2 years are explicitly excluded from the trial. Patients with a household member who has a history of active pulmonary TB should have had a thorough evaluation for TB prior to study enrolment as recommended by a local infectious disease specialist or published local guidelines of TB control agencies 6. Presence of a transplanted organ (with the exception of a corneal transplant >3 months prior to screening) 7. Malignancy within the past 5 years (except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence) 8. History of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (such as nodes in the posterior triangle of the neck, infra-clavicular, epitrochlear, or periaortic areas), or splenomegaly 9. Known recent substance abuse (drug or alcohol) 10. Poor tolerability of venepuncture required blood sampling during the study period 11. Planning to have surgery for RA or other significant surgery during the period of study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To compare the level of blood and synovial Th17 activity in participants with RA being treated with anti-TNF therapy between responders and non-responders. Samples of tissue from the ultrasound guided synovial biopsy, together with study specific blood sampling will be used to evaluate the pattern of activity shown in the Th17 pathway. Clinical response will be assessed on the basis of the EULAR response criteria using DAS28 (CRP) at week 24. The components of the DAS28(CRP) are the number of tender joints (28 joint count), the number of swollen joints (28 joint count), a Patient Global Health index (VAS), and the CRP (in mg/L). | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Predictability of clinical response based upon ultrasound assessments 2. To understand the mechanisms and effects of anti-TNF therapy on disease comparing responders and non-responders 3. To assess changes within the synovium over time, to be determined both at histomorphological and mRNA level 4. To investigate the cellular and angiogenic components in the relationship between the presence of ectopic lymphoneogenesis (ELN), ELN-associated markers, plus changes in cytokines and chemokines within the rheumatoid synovium and change in clinical disease activity 5. To assess B cell growth/modulating factors expression within the rheumatoid synovium and whether this correlates with autoantibody levels in the serum 6. To examine the dynamics of urine metabolites over time in relation to changes in clinical disease activity 7. Correlation of the change in IL-17/Th17 pathway activity and US assessment of synovitis by both grey-scale US and Power Doppler | — |
Countries
United Kingdom
Outcome results
None listed