Phase II, single-centre, open label, two parallel arm cohort randomised controlled trial (RCT) testing abatacept in a population of anti-CCP Ab positive individuals at moderate to high risk of developing IA according to a published risk score, already followed in the observational study 'CCP: Next Generation'
There is now evidence that the immunological disease process starts many years before the onset of clinically detectable inflammatory arthritis (IA). It is now a realistic goal to treat individuals in this pre-clinical phase with the possibility of arresting their progression to clinical disease. Individuals at risk of developing RA can be identified by the presence of CCP antibodies alongside other clinical features. In Leeds we have developed a prediction model that stratifies these individuals into at-risk vs. low risk. At present there are no treatments in this pathway until individuals develop IA. T-cells appear to be an appropriate target in at-risk individuals as they play a critical role in the generation and maintenance of autoimmunity. Abatacept (Orencia) is a selective T-cell modulator that blocks a co-stimulatory signal needed to activate T-cells and has an excellent safety profile.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
SINGLE
Enrollment
6
Abatacept sub-cutaneous injection 125mg at week 0 and once weekly thereafter for a maximum of 48 weeks
Institute of Rheumatic & Musculoskeletal Medicine, Chapel Allerton Hospital
Leeds, WEST Yorkshire, United Kingdom
Individuals who develop inflammatory arthritis
The percentage of individuals that have developed inflammatory arthritis at 48 weeks
Time frame: 48 weeks
Acute phase reactant levels
Acute phase reactant levels at weeks 12, 24, 36, 48, 60, 72, 84 and 96
Time frame: Weeks 12, 24, 36, 48, 60, 72, 84 and 96
Ultrasound synovitis and erosions
Power Doppler to record quantitative scoring 0-3 and erosions
Time frame: Weeks 24, 48, 72 and 96
Plain radiograph
Plain radiograph Sharp Van der Heide score 0-5
Time frame: Weeks 48 and 96
Patient-reported measures
Physician assessment of global disease activity 0-100mm
Time frame: Weeks 12, 24, 36, 48, 60, 72, 84 and 96
Joint swelling and tenderness
28/44 joint count of all tender and swollen joints via diagram
Time frame: Weeks 12, 24, 36, 48, 60, 72, 84 and 96
T-cell subset levels
T-cell subset levels
Time frame: Weeks 12, 24, 36, 48, 60, 72, 84 and 96
Toxicity levels
Toxicity levels according to the common toxicity criteria gradings
Time frame: Weeks 12, 24, 36, 48, 60, 72, 84 and 96
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