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

NCT04350216 | Unknown Phase 4

• 1 other identifier: SARIPET_2019.099
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Rheumatoid Arthritis; Atherosclerosis

Keywords

Positron Emission Tomography; chronic inflammatory state; interleukin (IL)-6; Computed Tomography

Outcome Measures

Primary Outcomes (2)

• Effect of Sarilumab on carotid atheroma plaque (effect on the inflammatory component) using ultrasound in patients with RA

  6 months

• Effect of Sarilumab on carotid atheroma plaque (effect on the mineralization) using ultrasound in patients with RA

  6 months

Secondary Outcomes (13)

• Change in PET/CT 18F-FDG uptake in the aortic wall

  6 months

• Change in PET/CT 18F-FNa uptake in the aortic wall

  6 months

• Determine disease activity with DAS 28 index (Rheumatoid arthritis disease activity index) with 4 items corresponding to low (DAS28 = 2.43), medium (DAS28 = 4.05), high (DAS28 = 6.32) or very high (DAS28 = 8.40) activity.

  6 months

• Determine disease activity with CDAI index ( number of painful and swollen joints with 28 joints, the activity assessment by the patient and the physician on a scale from 0 to 10 and the PCR in mg/dl)

  6 months

• Determine disease activity

  6 months

Study Arms (1)

Sarilumab therapy

EXPERIMENTAL

Patients will be treated every two weeks with 200 mg of the anti-IL human monoclonal antibody-6Rα Sarilumab (Kevzara) with or without conventional DMARDs. Sarilumab administration will be subcutaneous (abdomen, thigh, or upper arm). The dose will be reduced to 150 mg in the event of neutropenia, thrombocytopenia, and elevated liver enzymes.

Drug: Sarilumab 200 MG/1.14 ML Subcutaneous Solution [KEVZARA]

Interventions

Sarilumab 200 MG/1.14 ML Subcutaneous Solution [KEVZARA] DRUG

The treatment of sarilumab 200mg will be administered every two weeks subcutaneously. Each patient will be followed for 6 months from the start of treatment. The last administration of Sarilumab will be 2 weeks before the end of the study.

Sarilumab therapy

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years with active RA: DAS28\>3.2 and PCR levels ≥1 mg/dL
• Naïve to biological DMARDs or refractory to a single biological other than anti-IL-6 drugs.
• Only patients with plaques detected by carotid ultrasound (at least 1.5 mm) should have a PET/CT scan.
• Patients who are candidates for Sarilumab according to the summary of product characteristics
• Patients who sign the informed consent form.

You may not qualify if:

• Previous history of CV events.
• History of diabetes or chronic renal failure.
• Absolute neutrophil count \<2 x109/L.
• Platelet count \<150 x 103/μL.
• Elevated transaminases (ALT or AST \> 1.5 x LSN).
• Active infection, including localized infection.
• That have contraindicated the administration of Sarilumab.
• Patients who are participating in another clinical trial or research project.
• Refusal to participate in the study and to sign the consent form.
• Pregnant or nursing women, or women of childbearing age who are not using an effective method of contraception.

Sponsors & Collaborators

• Instituto de Investigación Marqués de Valdecilla: lead

MeSH Terms

Conditions

Arthritis, Rheumatoid; Atherosclerosis

Interventions

sarilumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Miguel Ángel González-Gay Mantecón, MDPhD

  hospital universitario marques Valdecilla

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Miguel Ángel González-Gay Mantecón, MDPhD

CONTACT

+34 942-202510; miguelaggay@hotmail.com

Lucia LAVIN ALCONERO

CONTACT

+34 942 203373; eclinicos5@idival.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2020
• First Posted: April 16, 2020
• Study Start: April 30, 2020
• Primary Completion: October 30, 2020
• Study Completion: April 30, 2021
• Last Updated: April 27, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share