Effects of Abatacept on Myocarditis in Rheumatoid Arthritis
Condition: Rheumatoid Arthritis; Myocardial Inflammation
MeSH terms: Arthritis; Arthritis, Rheumatoid; Myocarditis; Inflammation
Intervention: Abatacept; Adalimumab
Intervention description: 125 MG/ML subcutaneous injections; 40 Mg/0.8 mL Subcutaneous Kit
Intervention MeSH terms: Adalimumab; Abatacept
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: RA patients will be randomized in an unblinded, 1:1 ratio to treatment with abatacept vs adalimumab. A cardiac FDG PET/CT will be performed at baseline and 16(±2) weeks post-biologic treatment. T cell subpopulations associated with myocardial FDG uptake will be evaluated at both points in time with their transcriptional phenotype outlined by RNAseq.
Masking: None (Open Label)
Masking description: Unblinded- open label
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: CTLA4-Ig; Abatacept; Myocarditis; RA

Summary:

      This study aims to evaluate the effects of abatacept, a CTLA4-Ig fusion protein that binds
      cluster of differentiation antigen 80 (CD80)/86 (B7-1/B7-2), on subclinical myocarditis in
      rheumatoid arthritis (RA) through its effect on T cell subpopulations. RA patients without
      clinical CVD, biologic naïve, and with inadequate response to methotrexate (MTX), will
      undergo cardiac fluorodeoxyglucose (FDG) positron emission tomography (PET)/computerized
      tomography (CT) imaging to assess myocardial inflammation. Studies that investigate the
      impact of treatment on subclinical myocarditis in RA, a possible contributor to heart
      failure, while exploring potential underlying mechanisms (i.e., different T cell
      subpopulations), are needed for a better understanding of their relevance in the pathogenesis
      of heart failure in RA and survival improvement in these patients with excess risk for
      cardiovascular death. If the investigator hypothesis is confirmed and treatment with
      abatacept decreases and/or suppresses or prevents myocardial inflammation in RA, this will
      have multidisciplinary implications that could lead to changes in the current management of
      RA patients at high risk for cardiovascular events. Similarly, identification of T cell
      subpopulations in RA patients with myocardial FDG uptake will shed light into the underlying
      cellular mechanisms of myocardial injury and serve to guide the use of therapies that prevent
      their pathogenicity. The objectives of this study are to compare the change in myocardial FDG
      uptake in RA patients treated with abatacept vs adalimumab, and identify T cell
      subpopulations associated with myocardial FDG uptake in each treatment arm. RA patients will
      be randomized in an unblinded, 1:1 ratio to treatment with abatacept vs adalimumab. A cardiac
      FDG PET/CT will be performed at baseline and 16 weeks post-biologic treatment. T cell
      subpopulations associated with myocardial FDG uptake will be evaluated at both points in time
      with their transcriptional phenotype outlined by RNA sequencing.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent signed by the subject.

          -  Patients age > 18 years.

          -  Fulfilling the American College of Rheumatology 2010 classification criteria for RA.

          -  MTX for ≥ 8 weeks at ≥ 15mg weekly or on at least 7.5mg of methotrexate weekly for ≥8
             weeks with a documented intolerance of higher MTX doses, and on a stable dose for the
             previous 4 weeks;

          -  Naïve to biologic treatment.

          -  If the subject is a woman with childbearing potential, a urine sample will be taken
             for a pregnancy test. The results of the pregnancy test must be negative.

        Exclusion Criteria:

          -  Prior biologic use.

          -  Any prior self-reported physician diagnosed CV event (myocardial infarction; angina;
             stroke or Transient Ischemic Attack (TIA); heart failure; prior CV procedure (i.e.,
             coronary artery bypass graft, angioplasty, valve replacement, pacemaker).

          -  Active history of cancer.

          -  Prior use of immune checkpoint inhibitors.

          -  Known pregnancy, HIV, hepatitis B, hepatitis C, active (or untreated latent)
             tuberculosis.