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

Imperial College London

Status

Completed

Conditions

Psoriatic Arthritis

Ankylosing Spondylitis

Rheumatoid Arthritis

Treatments

Drug: anti-TNF therapy (etanercept or adalimumab)

Study type

Observational

Funder types

Other

Identifiers

NCT01060098

2104091

Details and patient eligibility

About

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.

Full 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.

Enrollment

48 patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Only anti-TNF naïve patients will be included in this study
Patients between 18 to 80 years of age
Patients due to start treatment with anti-TNF blocking agents - etanercept or adalimumab

Patients with rheumatoid arthritis

Only patients meeting the 1987 American College of Rheumatology (ACR) revised classification criteria for rheumatoid arthritis will be included
Patients should have active rheumatoid arthritis, defined by an initial DAS28 score >5.1
Patients should have at least 1 joint suitable for synovial biopsy
Patients can be on concurrent DMARDs but they should have been on a stable dose of DMARD for at least 1 month prior to study entry
Patients can be on a concurrent dose of glucocorticoids (up to 10mg daily) and they should have been on a stable dose for at least 4 weeks prior to study entry

Patients with psoriatic arthritis

Patients should have a secure diagnosis of psoriatic arthritis determined by a rheumatologist
Patients with psoriatic arthritis included in this study should have evidence of concurrent psoriatic skin lesions at the time of study entry
Patients should have at least one joint suitable for synovial biopsy
Patients can be on concurrent DMARDs - they should be on a stable dose of DMARD for at least 1 month prior to study entry

Patients with Ankylosing spondylitis

Patient should fulfil the Modified New York Criteria for diagnosis of ankylosing spondylitis
Patients can be on concurrent NSAIDs
Patients can be on concurrent DMARDs - they should be on a stable dose of DMARD for at least 1 month prior to study entry

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