THERAPIST Version 1.0
Research type
Research Study
Full title
Investigating relationships between IL-17, Th17 pathway activation and therapeutic response to TNF inhibition in RA patients.
IRAS ID
147240
Contact name
Costantino Pitzalis
Contact email
Sponsor organisation
Queen Mary University of London
Duration of Study in the UK
2 years, 0 months, 0 days
Research summary
Though anti-TNFa therapy has transformed the treatment of rheumatoid arthritis (RA), 30-40% patients do not respond to this treatment. Currently, there are no tests capable of predicting response and the mechanisms of non-response remain unknown. This leaves a major unmet need and a considerable health and economic burden. In the UK alone, RA drugs cost the NHS £560 million, while RA total annual economic impact is estimated £4.2 billion (NAO).
The THERAPIST study aims to address this major unmet need by exploring the capacity of disease tissue (synovium) and peripheral blood biomarkers to predict response prior to anti-TNFa therapy initiation and to understand the mechanisms of response/non-response. In addition THERAPIST will characterise the role of IL-17 / Th-17 pathway (primary hypothesis) and, through a powerful hypothesis-free discovery investigation, potentially unveil new therapeutic targets.Fifty 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 following informed consent.
Clinical responses will be assessed by standard/validated tools such as 28 tender-swollen joint count integrated into the Disease Activity Score (DAS28), as well as objective ultrasound joint imaging.Biological responses will be measured in the disease tissue (synovial biopsy sub-study) in 20 patients consenting to an ultrasound-guided, minimally invasive, safe, well-tolerated procedure, as we described (Kelly et al. Ann Rheum Disease 2013) and in peripheral blood of all 50 patients as comparators.
The biopsy sub-study is essential to provide disease tissue for the proposed investigation, as 30 years of research looking for peripheral blood predictive biomarkers have proven unsuccessful (unfavourable signal to noise ratio). It is clear that direct sampling of the diseased tissue, as successfully done in other disease areas can provide fundamental evidence to inform therapeutic decision-making (e.g. Tamoxifen in ER+ve breast cancer).REC name
South Central - Hampshire B Research Ethics Committee
REC reference
15/SC/0045
Date of REC Opinion
2 Feb 2015
REC opinion
Favourable Opinion