Rituximab in patients with acute ST-elevation myocardial infarction: an experimental medicine safety study
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Le résumé fourni par la source
AIMS: In pre-clinical models of acute myocardial infarction (MI), mature B cells mobilize inflammatory monocytes into the heart, leading to increased infarct size and deterioration of cardiac function, whilst anti-CD20 antibody-mediated depletion of B cells limits myocardial injury and improves cardiac function. Rituximab is a monoclonal anti-CD20 antibody targeted against human B cells. However, its use in cardiovascular disease is untested and is currently contraindicated. Therefore, we assessed the safety, feasibility, and pharmacodynamic effect of rituximab given to patients with acute ST-elevation MI (STEMI). METHODS AND RESULTS: Rituximab in patients with acute ST-elevation myocardial infarction (RITA-MI) was a prospective, open-label, dose-escalation, single-arm, phase 1/2a clinical trial, which tested rituximab administered as a single intravenous dose in patients with STEMI within 48 h of symptom onset. Four escalating doses (200, 500, 700, and 1000 mg) were used. The primary endpoint was safety, whilst secondary endpoints were changes in circulating immune cell subsets including B cells, and cardiac and inflammatory biomarkers. A total of 24 patients were dosed. Rituximab appeared well tolerated. Seven serious adverse events were reported, none of which were assessed as being related to the rituximab infusion. Rituximab caused a mean 96.3% (95% confidence interval 93.8-98.8%) depletion of circulating B cells within 30 min of starting the infusion. Maximal B-cell depletion was seen at Day 6, which was significantly lower than baseline for all doses (P < 0.001). B-cell repopulation at 6 months was dose-dependent, with modulation of returning B-cell subsets. Immunoglobulin (IgG, IgM, and IgA) levels were not affected during the 6 months of follow-up. CONCLUSIONS: A single infusion of rituximab appears safe when given in the acute STEMI setting and substantially alters circulating B-cell subsets. We provide important new insight into the feasibility and pharmacodynamics of rituximab in acute STEMI, which will inform further clinical translation of this potential therapy. CLINICAL TRIAL REGISTRATION: NCT03072199 at https://www.clinicaltrials.gov/.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Rituximab in patients with acute ST-elevation myocardial infarction: an experimental medicine safety study
- Date Crossref
- 30/03/2021
- Éditeur
- Oxford University Press (OUP)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Cambridge Department of Medicine pays non établi dans la noticeUniversité ou école supérieure
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Papworth Hospital NHS Foundation Trust Department of Cardiology pays non établi dans la noticeÉtablissement de santé
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Papworth Hospital Papworth Trials Unit Collaboration pays non établi dans la noticeÉtablissement de santé
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Inserm pays non établi dans la noticeOrganisme public
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Université Paris Cité pays non établi dans la noticeUniversité ou école supérieure
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Paris Cardiovascular Research Center pays non établi dans la noticeStructure de recherche
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Medical University of Vienna Department of Laboratory Medicine pays non établi dans la noticeUniversité ou école supérieure
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Université de Paris pays non établi dans la noticeUniversité ou école supérieure
Department of Medicine — University of Cambridge, Department of Cardiology — Papworth Hospital NHS Foundation Trust et Papworth Trials Unit Collaboration — Papworth Hospital, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.