Ticagrelor in Methotrexate-Resistant Rheumatoid Arthritis

The two main goals of this study are to demonstrate the heightened cardiovascular risk in RA
by comparing platelet activity, inflammation and endothelial function in baseline rheumatoid
arthritis versus age- and sex-matched patients with osteoarthritis; and 2) to demonstrate the
effect of ticagrelor in rheumatoid arthritis by the pre- and post- measures of clinical RA
severity, platelet activity, inflammation and endothelial function in rheumatoid arthritis
before and after ticagrelor therapy.

Inclusion Criteria

RA cohort

- Receiving MTX at stable doses of 10 to 25 mg weekly for at least 12 weeks

- Have a DAS28 of 3.2 or higher (The level of disease activity is considered to be low
if the DAS28 is 3.2 or less) (Prevoo et al., 1995)

OA cohort

- Diagnosis of osteoarthritis made by physician.

Exclusion Criteria:

RA cohort

- History of sensitivity to study medications or any of their excipients

- Previous intolerance to MTX

- Current treatment with antiplatelet therapy

- Absolute indication for anti-platelet therapy

- Need for chronic oral anticoagulant therapy

- Severe hepatic impairment (eg, ascites and/or clinical signs of coagulopathy)

- Renal failure (eGFR <30 or requiring dialysis)

- A known bleeding diathesis, hemostatic or coagulation disorder, or prior major
bleeding

- Prior stroke

- Active pathological bleeding

- History of intracranial haemorrhage

- Life expectancy <12 months based on investigator's judgement

- Patients considered to be at risk of bradycardic events (e.g., known sick sinus
syndrome or second or third degree atrioventricular [AV)] block) unless already
treated with a permanent pacemaker

- Anemia (hematocrit < 27%)

- Platelet count < 100,000/ml

- Concomitant use of strong CYP 3A inhibitors or inducers

- History of thrombocytopenia or neutropenia

- Pregnant or nursing women, or females with a positive pregnancy test at screening

- Females of child bearing potential not using acceptable method of birth control prior
to or during study

- Concern for inability of the patient to comply with study procedures and/or follow up
(eg, alcohol or drug abuse)

OA cohort:

- History of sensitivity to study medications or any of their excipients

- Current treatment with antiplatelet therapy

- Absolute indication for anti-platelet therapy

- Need for chronic oral anticoagulant therapy

- Severe hepatic impairment (eg, ascites and/or clinical signs of coagulopathy)

- Renal failure (eGFR <30 or requiring dialysis)

- A known bleeding diathesis, hemostatic or coagulation disorder, or prior major
bleeding

- Prior stroke

- Active pathological bleeding

- History of intracranial haemorrhage

- Life expectancy <12 months based on investigator's judgement

- Anemia (hematocrit < 27%)

- Platelet count < 100,000/ml

- History of thrombocytopenia or neutropenia

- Pregnant or nursing women, or females with a positive pregnancy test at screening

- Females of child bearing potential not using acceptable method of birth control prior
to or during study

- Concern for inability of the patient to comply with study procedures and/or follow up
(eg, alcohol or drug abuse)