Ankylosing Spondylitis, Psoriatic Arthritis, Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid arthritis
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.
Interventions
DRUGanti-TNF therapy (etanercept or adalimumab)
Biological DMARD
Sponsors
Imperial College London
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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)). |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rheumatoid Arthritis Participants with Rheumatoid arthritis | 25 |
| Ankylosing Spondylitis Participants with Ankylosing spondylitis | 15 |
| Psoriatic Arthritis Participants with psoriatic arthritis | 8 |
| Total | 48 |
Baseline characteristics
| Characteristic | Ankylosing Spondylitis | Psoriatic Arthritis | Total | Rheumatoid Arthritis |
|---|---|---|---|---|
| Age, Continuous | 36.4 years STANDARD_DEVIATION 11.8 | 50.9 years STANDARD_DEVIATION 8.4 | 48.23 years STANDARD_DEVIATION 10.6 | 57.4 years STANDARD_DEVIATION 11.7 |
| Race and Ethnicity Not Collected | — | — | 0 Participants | — |
| Region of Enrollment United Kingdom | 15 participants | 8 participants | 48 participants | 25 participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 26 Participants | 18 Participants |
| Sex: Female, Male Male | 12 Participants | 3 Participants | 22 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 15 | 0 / 8 |
| other Total, other adverse events | 0 / 25 | 0 / 15 | 0 / 8 |
| serious Total, serious adverse events | 0 / 25 | 0 / 15 | 0 / 8 |
Outcome results
Primary
Measurement of Effector T Helper Type 17 Cells in Peripheral Blood
The frequency of circulating Th17 cells was determined by IL17 enzyme-linked immunospot assay (Elispot) and flow cytometry (fluorescence-activated cell sorting (FACS)).
Time frame: Week 0, Week 12
Population: Patients with RA were studied at protocol visits during the initial 12 weeks of anti-TNF treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rheumatoid Arthritis | Measurement of Effector T Helper Type 17 Cells in Peripheral Blood | Week 0 | 466.4 spSFC/10^6 | Standard Error 277.6 |
| Rheumatoid Arthritis | Measurement of Effector T Helper Type 17 Cells in Peripheral Blood | Week 12 | 759.8 spSFC/10^6 | Standard Error 510 |
| Ankylosing Spondylitis | Measurement of Effector T Helper Type 17 Cells in Peripheral Blood | Week 0 | 432 spSFC/10^6 | Standard Error 474 |
| Ankylosing Spondylitis | Measurement of Effector T Helper Type 17 Cells in Peripheral Blood | Week 12 | 651 spSFC/10^6 | Standard Error 532 |
| Psoriatic Arthritis | Measurement of Effector T Helper Type 17 Cells in Peripheral Blood | Week 0 | 450 spSFC/10^6 | Standard Error 276 |
| Psoriatic Arthritis | Measurement of Effector T Helper Type 17 Cells in Peripheral Blood | Week 12 | 609 spSFC/10^6 | Standard Error 373 |
Comparison: week 0 compared to week 12p-value: 0.003Wilcoxon (Mann-Whitney)
Comparison: week 0 compared to week 12p-value: 0.04Wilcoxon (Mann-Whitney)
Comparison: week 0 compared to week 12p-value: 0.48Wilcoxon (Mann-Whitney)