T Cells and TNF (Tumor Necrosis Factor): The Impact of TNF Blockade

Completed

Brief Summary: We aim to translate these findings into patients with rheumatoid arthritis and other conditions treated with anti-TNF (anti-tumor necrosis factor) therapy, such as psoriatic arthritis and ankylosing spondylitis. Patients from rheumatology clinics within NHS (National Health Service) trusts will be recruited. We will correlate disease activity assessed by clinical parameters, ultrasonography, and questionnaires with biomarkers in the blood and target tissues, such as synovium and skin.

Detailed Description: Inflammatory arthritis particularly rheumatoid arthritis (RA), psoriatic arthritis and ankylosing spondylitis are potentially disabling conditions which cause joint pain, swelling and deformity and treatments are aimed at preventing these complications. Although treatment has improved with the advent of anti TNF alpha therapies, up to 30% of patients fail to respond to this treatment and in others, treatment is associated with significant side effects. The precise mechanisms of this remain unclear. In addition, there are no sensitive methods available to monitor or predict disease response to treatment aside from testing inflammatory markers in the blood. Understanding the mechanism of action and what governs response to anti TNF therapy will allow development of more specific therapies for inflammatory arthritis. Work in animal models of rheumatoid arthritis has characterised a novel cell type, Th17 cells, important in the inflammatory cascade which are affected in a particular way by anti TNF therapies and may underpin their mechanism of action and side effects.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Patients who have been previously treated with anti-TNF therapy for whatever reason
Patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis who do not fulfil the diagnostic criteria for these conditions as above
Patient who have received an intra-articular injection of steroids or have received an intra-muscular injection of depot steroid to treat disease flare in the preceding 4 weeks prior to commencing anti-TNF therapy.
Patients with intercurrent, active infection of any type, excluding the common cold

Arm && Interventions

Group	Intervention	Description
Rheumatoid arthritis	anti-TNF therapy (etanercept or adalimumab)	Participants with Rheumatoid arthritis
Psoriatic arthritis	anti-TNF therapy (etanercept or adalimumab)	Participants with Psoriatic arthritis
Ankylosing spondylitis	anti-TNF therapy (etanercept or adalimumab)	Participants with Ankylosing spondylitis

Primary Outcome Measures

Name	Time	Method
Measurement of Effector T Helper Type 17 Cells in Peripheral Blood	Week 0, Week 12	The frequency of circulating Th17 cells was determined by IL17 enzyme-linked immunospot assay (Elispot) and flow cytometry (fluorescence-activated cell sorting (FACS)).

Secondary Outcome Measures