Effects of Abatacept on Myocarditis in Rheumatoid Arthritis

• Status: Recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This study aims to evaluate the effects of abatacept, a CTLA4-Ig fusion protein that binds 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 FDG PET/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 RNAseq.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Columbia University
• Collaborator: Bristol-Myers Squibb
• Treatments: Abatacept; Adalimumab

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.