Effect of Sarilumab on Atherosclerotic Disease Assessed by PET/CET in Patients With RA (SARIPET)

• Status: Not yet recruiting
• Trial end date: 2021-04-30
• Target enrollment: 0
• Participant gender: All

Summary

Rheumatoid arthritis (RA) is a condition associated with a high incidence of cardiovascular disease (CV), primarily as a result of accelerated atherosclerosis . Patients with RA also have a high prevalence of metabolic syndrome (MS) The state of chronic inflammation in RA patients contributes to increased CV risk.

Deregulation of both genetic and serological adipocines, MS biomarkers, and biomarkers of endothelial activation and inflammation also contributes to the increased CV risk in these patients.

An increased incidence of abnormal carotid intima-media thickness (cIMT) values and carotid plaques, considered surrogate markers of subclinical atherosclerotic disease, has also been described in patients with RA.

Positron emission tomography/computed tomography (PET/CT) is a noninvasive imaging technique useful for the evaluation of inflammation (by 18F-FDG uptake) and mineralization (by 18F-NaF uptake) in carotid atheroma plaque.

Atherosclerosis and RA share many common inflammatory pathways, and the mechanisms that lead to synovial inflammation are similar to those seen in atherosclerotic plaque.

Interleukin (IL)-6 is a key pro-inflammatory cytokine involved in both the pathophysiology of RA and the development of atherosclerosis.

Sarilumab is a human monoclonal antibody against the IL-6 receptor that has been shown to be effective in patients with RA, improving symptoms, as well as at the functional and radiographic levels.

Treatment with IL-6 receptor inhibitors has been described to result in a modulation of lipid metabolism, mediated by a reduction in lipoprotein (a) (Lp(a)) and an improvement in the anti-oxidant function of high-density lipoprotein (HDL) . In this regard, Sarilumab may have beneficial effects in RA patients on MS, which is implicated in the development of atherosclerotic disease.

Information regarding the beneficial effect of IL-6 receptor blockade on atheroma plaque formation and its effect at the vascular level in RA patients is scarce.

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

Details

• Lead Sponsor: Instituto de Investigación Marqués de Valdecilla

Criteria

Inclusion Criteria:

1. Age ≥18 years with active RA: DAS28>3.2 and PCR levels ≥1 mg/dL

2. Naïve to biological DMARDs or refractory to a single biological other than anti-IL-6 drugs.

3. Only patients with plaques detected by carotid ultrasound (at least 1.5 mm) should have a PET/CT scan.

4. Patients who are candidates for Sarilumab according to the summary of product characteristics

5. Patients who sign the informed consent form.

Exclusion Criteria:

1. Previous history of CV events.

2. History of diabetes or chronic renal failure.

3. Absolute neutrophil count <2 x109/L.

4. Platelet count <150 x 103/μL.

5. Elevated transaminases (ALT or AST > 1.5 x LSN).

6. Active infection, including localized infection.

7. That have contraindicated the administration of Sarilumab.

8. Patients who are participating in another clinical trial or research project.

9. Refusal to participate in the study and to sign the consent form.

10. Pregnant or nursing women, or women of childbearing age who are not using an effective method of contraception.