A single rituximab infusion was well tolerated among patients with acute ST elevation myocardial infarction (STEMI) and substantially changed subsets of circulating B lymphocytes, according to a prospective, open-label, dose-escalating, phase 1/2a clinical trial published in Cardiovascular Research.
The rituximab in patients with acute STEMI (RITA-MI) trial recruited patients from the Royal Papworth Hospital in the UK between September 2017 and February 2019. Patients (N=24) with acute STEMI who underwent a successful primary percutaneous coronary intervention (PCI) within 24 hours of symptoms were administered 100 mg of methylprednisolone intravenously over 30 minutes, a 10-mg intravenous injection of chlorpheniramine, and 1 g oral acetaminophen 30 minutes prior to a 50 mg/hour infusion of rituximab for 30 minutes that increased by 50 mg/hour every 30 minutes to a maximum of 400 mg/hour if tolerated. Maximum total doses were 200, 500, 700, and 1000 mg for 6 patients in each group. Clinical outcomes and safety were assessed.
Average patient age ranged among groups between 52.5 and 65 years, between 83% and 100% were men, and all were White. Patients received their rituximab infusion at an average of 43.1 (standard deviation [SD], 7.9) hours after symptom onset.
All but 4 patients had an adverse event, and 7 events were serious. Among the serious events, 5 were unrelated to rituximab infusions and 2 were associated with an unrelated PCI procedure. Three patients had infusion-related reactions causing the rate of infusion to be decreased for two of the patients. Infections were reported by 4 patients (flu or cold: n=2, urinary tract infection: n=1, lower respiratory infection: n=1).
Rituximab resulted in a 96.3% (95% CI, 93.8% to 98.8%) depletion of B cell count within 30 minutes of infusion. Stratified by dose, all were significantly lower compared with baseline (all P £.0004).
At 6 hours, B cell counts rebounded in a dose-dependent relationship for the recipients of 200, 500, and 700 mg. At day 6 and 14, B cell counts remained low among the high-dose group. At 6 months, recovery was 57.8% for the 200 mg, 20.8% for the 500-mg, 22.6% for the 700-mg, and 3.9% for the 1000-mg cohorts. Compared with baseline, the 200-mg cohort did not differ (P =.63) and compared with the 1000-mg group, the B cell count differed significantly (P =.02).
After infusion, lymphocyte counts decreased but recovered by day 6. At 6 months, troponin I, high sensitivity C-reactive protein, N-terminal pro-brain natriuretic peptide, interleukin-6, total cholesterol, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol were decreased. No changes were observed for eosinophils, basophils, regulatory T cells, immunoglobulin (Ig)G, IgM, or IgA.
At follow-up, left ventricular ejection fraction had improved (46.5% vs 54.3%).
This study was limited by its small sample size, single-center design, and lack of a control arm.
The study authors concluded a single infusion of rituximab among patients with acute STEMI was safe and feasible, justifying progression to trial phase 2b.
Disclosure: Two study authors hold a patent for the treatment of atherosclerosis. Please refer to the original article for a full list of disclosures.
Zhao TX, Aetesam-ur-Rahman M, Sage AP, et al. Rituximab in Patients With Acute ST-Elevation Myocardial Infarction (RITA-MI): an experimental medicine safety study. Cardiovasc Res. Published online March 30, 2021. 2021. doi:10.1093/cvr/cvab113