Abatacept in Individuals Who aRe Considered At Risk of Developing Inflammatory Arthritis

Inclusion Criteria:

• Participant in Leeds CCP 'Next Generation' observational cohort who has testedpositive for anti-CCP Ab and accepted to be approached for a interventional study

• Age >18 years old.

• At moderate to high risk of progression to IA (see below).

• Consents to be contacted in future for an interventional study

A prediction model will be used to risk stratify individuals based on the following predictors:

1. Tenderness of ≥1 small joint of the hands or feet defined by the physician (onepoint)

2. Early morning stiffness ≥30 minutes (one point)

3. RF and/or anti-CCP Ab concentration >3x upper limit of normal. (2 points) Theparticipant's risk will be calculated according to the model suggested by Rakieh etal. (1). Those with a score of ≥3 out of 4 will be eligible to be randomised.

• For the intervention arm:

• Randomised to intervention arm

• Consents to commence Abatacept therapy (if not, will remain in CCPNext-generation study)

• For the control arm:

• Randomised to the control arm

• Will remain in the CCP Next-generation study

Exclusion Criteria:

For both the intervention and control arms:

• Previous diagnosis of RA or other form of inflammatory arthritis including, but notlimited to SLE, psoriatic arthritis, ankylosing spondylitis, gout or pyrophosphatearthropathy and including current treatment with DMARDs or biological therapy

• Clinical synovitis on clinical examination by a rheumatologist

• Presence of concomitant illness likely to require systemic glucocorticosteroidtherapy during the study, in the opinion of the investigator

• Treatment with an intravenous, intramuscular, intrabursal or intraarticularcorticosteroid within 12 weeks prior to randomization

• Co-morbidities requiring chronic treatment with immunosuppressive or immunemodulating therapy.

• Women in the intervention arm who get pregnant during the study will be withdrawnfrom treatment and followed for the duration of the pregnancy for safety purposes.All participants who get pregnant will continue to be followed up in clinic asstandard NHS care to collect secondary end point data

• Evidence of active or latent bacterial or viral infection at the time of potentialenrolment, including human immunodeficiency or herpes zoster virus orcytomegalovirus that resolved less than 2 months prior to enrolment

• Individuals with palindromic rheumatism

For the intervention arm only:

• History of acute allergic reactions to biologic therapies or immunoglobulins

• Subjects with current symptoms of severe, progressive, or uncontrolled renal,hepatic, hematologic, gastrointestinal, pulmonary, cardiac, neurologic, or cerebraldisease, whether or not related to RA and which, in the opinion of the investigator,might place a subject at unacceptable risk for participation in the study

• Subjects who have at any time received treatment with any investigational drugwithin 28 days of the first dose of study drug

• Subjects who test positive for Hepatitis B, C or HIV.

• Subjects with tuberculosis (TB), including those at high risk of TB, chronic viralinfections, recent serious bacterial infections, subjects receiving livevaccinations within 3 months of the anticipated first dose of study medication, orthose with chronic illnesses that would, in the opinion of the investigator, put theparticipant at risk

• Subjects who currently abuse drugs or alcohol

• Subjects with a history of cancer in the last 5 years, other than non-melanoma skincell cancers cured by local resection or carcinoma in situ

• Scheduled for or anticipating joint replacement surgery

• Men or women unwilling to use an acceptable method of contraception (detailed in 7.1.4) to avoid pregnancy for up to 14 weeks after the last dose of trial medication

• Women of childbearing potential with a positive serum or urine pregnancy test within 48 hours prior to the baseline visit. Women of child bearing potential are definedas women who have had any menstrual bleeding in the last 24 months and who have nothad a hysterectomy or surgical sterilisation

• Evidence of active or latent bacterial or viral infection at the time of potentialenrolment, including human immunodeficiency or herpes zoster virus orcytomegalovirus that resolved less than 2 months prior to enrolment

• Inadequate haematological, hepatic or renal function within 28 days of treatment:

• Haemoglobin <8.5 g/dL

• White blood cells <3000/mm3

• Platelets <100,000/mm3

• Serum creatinine, ALT or AST >2 times upper limit of normal

• Any other laboratory test result that, in the opinion of the studyinvestigator, might place the participant at unacceptable risk forparticipation in the study