Ticagrelor in Methotrexate-Resistant Rheumatoid Arthritis

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 lowif 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 majorbleeding
• 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 sinussyndrome or second or third degree atrioventricular [AV)] block) unless alreadytreated 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 priorto 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 majorbleeding
• 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 priorto or during study
• Concern for inability of the patient to comply with study procedures and/or follow up (eg, alcohol or drug abuse)