Ticagrelor in Methotrexate-Resistant Rheumatoid Arthritis
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Ticagrelor; MTX therapy
Intervention MeSH terms: Ticagrelor
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Methotrexate (MTX); Ticagrelor

Summary:

      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.
    

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)