Ticagrelor in Methotrexate-Resistant Rheumatoid Arthritis

This is an open label study to assess the improvement in the Disease Activity Score for 28-joint counts (DAS28) with ticagrelor given at 90 mg twice daily in patients with RA who have active disease despite MTX therapy (as defined by the inclusion/exclusion criteria). There will also be a cross sectional analysis of baseline platelet activity in subjects with rheumatoid arthritis and osteoarthritis. Subjects in the OA cohort will not receive any study medication, and will only have one study visit.

Patients will receive 90 mg ticagrelor orally bid. The patients will receive drug for 30-days. Methotrexate dose will remain stable throughout the study duration.

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.

Eligibility Criteria:
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)