PMC9218605_01
Case report timeline. BMI, body mass index; BP, blood pressure; CAD, coronary artery disease; 18FDG PET/CT, 18Fluorodeoxyglucose positron emission tomography/computed tomography; HbA1c, glycated hemoglobin; hsCRP, high-sensitivity C-reactive protein; IL-6, interleukin-6; i.v., intravenously.
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Table 1; Figure 1).
PMC9218605_02
PMC9218605_03
PMC9218605_04
Case report timeline. BMI, body mass index; BP, blood pressure; CAD, coronary artery disease; 18FDG PET/CT, 18Fluorodeoxyglucose positron emission tomography/computed tomography; HbA1c, glycated hemoglobin; hsCRP, high-sensitivity C-reactive protein; IL-6, interleukin-6; i.v., intravenously.
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Table 1; Figure 1).
Inhibition of IL-6 trans-signalling reduces arterial wall inflammation and macrophage infiltration of atherosclerotic plaques in end-stage atherosclerosis. (A) Arterial wall inflammation in the carotid arteries of the patient (1) at baseline and (2) 11 weeks after the beginning of olamkicept treatment (6 infusions of 600 mg i. v. biweekly; Table 1). In the representative axial computed tomography (CT), 18fluorodeoxyglucose positron emission tomography (18FDG PET), and fused images (18FDG PET/CT), regions of interest are highlighted by red (artery) and blue circles (vein). Mean and maximum target-to-background ratio (TBRmean and TBRmax) are listed below. (B,C) New analyses of samples from a previous study in a murine model of experimental atherosclerosis (B) Representative MOMA-2-stained (macrophage-positive) lesions in aortic root sections (scale bars = 250 microm) of Ldlr
-/- mice (n = 4 to n = 7 per group) after 12 weeks on a high-fat, high-cholesterol diet followed by another 12 weeks on the same diet combined with vehicle or olamkicept treatment (0.5 mg/kg intraperitoneally, twice weekly); (C) MOMA-2 levels expressed as percentage (mean, standard deviation) of the MOMA-positive (+) total plaque area at baseline (B) or after vehicle (V) or olamkicept treatment (O); *, p < 0.05; ns, not significant.
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The patient presented with an atherosclerosis characterized by Lp(a)-cholesterol and hsCRP. The arterial wall inflammation detected by 18FDG PET/CT at baseline was strongly reduced after 3 months by 6 infusions of olamkicept (Figure 2A) without observing changes in lipoprotein distribution. This is in contrast to evolocumab treatment, where a large reduction in LDL cholesterol and a small reduction in Lp(a) levels did not lead to a decrease in arterial wall inflammation. Similar to the 18FDG PET/CT findings in this patient, olamkicept decreased the amount of MOMA-2-positive plaque macrophages in atherosclerotic lesions also in samples from mice with established experimental atherosclerosis which had been produced in our previous mechanistic trial but not yet been analysed in this regard (Figures 2B,C).
PMC9218605_05