Tocilizumab induced a rapid reduction in neutrophils and attenuated neutrophil function in STEMI patients, which was associated with improved myocardial salvage and lower peak troponin T.
RCT (n=199)
randomised
Does tocilizumab alter immune cell profiles and improve myocardial salvage in patients with STEMI?
Tocilizumab induces a rapid reduction in neutrophils in STEMI patients, which correlates with improved myocardial salvage, suggesting a potential mechanism for its cardioprotective effects.
Background We recently showed that interleukin (IL)-6 inhibition by tocilizumab improves myocardial salvage in ST-elevation myocardial infarction (STEMI). However, the mechanisms for this effect are not clear. Methods In this exploratory sub-study of the ASSAIL-MI trial, we examined leukocyte differential counts and their relation to myocardial salvage and peak troponin T (TnT) in STEMI patients randomised to tocilizumab ( n = 101) or placebo ( n = 98). We performed RNA-sequencing on whole blood ( n = 40) and T cells ( n = 20). B and T cell subpopulations were examined by flow cytometry ( n = 69). Findings (i) STEMI patients had higher neutrophil counts at hospitalisation compared with stable angina patients. (ii) After percutaneous coronary intervention there was a gradual decline in neutrophils, which was significantly more pronounced in the tocilizumab group. (iii) The decrease in neutrophils in the tocilizumab group was associated with improved myocardial salvage and lower peak TnT. (iv) RNA-sequencing suggested that neutrophil function was also attenuated by tocilizumab. (v) B and T cell sub-populations changed only minimally after STEMI with minor effects of tocilizumab, supported as well by RNA-sequencing analyses of T cells. (vi) However, a low CD8 + count was associated with improved myocardial salvage in patients admitted to the hospital > 3 h after symptom onset. Interpretation Tocilizumab induced a rapid reduction in neutrophils and seemed to attenuate neutrophil function in STEMI patients potentially related to the beneficial effects of tocilizumab on myocardial salvage. Funding South-Eastern Norway Regional Health Authority (Nos. 2019067, 2017084), the Central Norway Regional Health Authority and Norwegian Research Council (No. 283867).
Huse et al. (Sat,) conducted a rct in ST-elevation myocardial infarction (STEMI) (n=199). Tocilizumab vs. Placebo was evaluated on Leukocyte differential counts and their relation to myocardial salvage and peak troponin T. Tocilizumab induced a rapid reduction in neutrophils and attenuated neutrophil function in STEMI patients, which was associated with improved myocardial salvage and lower peak troponin T.