MDCO-216 Does Not Induce Adverse Immunostimulation, in Contrast to Its Predecessor ETC-216.
Cardiovasc Drugs Ther
; 31(4): 381-389, 2017 Aug.
Article
in En
| MEDLINE
| ID: mdl-28844118
PURPOSE: Aim of this study was to demonstrate that MDCO-216 (human recombinant Apolipoprotein A-I Milano) does not induce adverse immunostimulation, in contrast to its predecessor, ETC-216, which was thought to contain host cell proteins (HCPs) that elicited an inflammatory reaction. METHODS: Data were taken from a clinical trial in which 24 healthy volunteers (HV) and 24 patients with proven stable coronary artery disease (sCAD) received a single intravenous dose of MDCO-216, ranging 5-40 mg/kg. Additionally, whole blood from 35 HV, 35 sCAD patients and 35 patients requiring acute coronary intervention (aCAD group) was stimulated ex vivo with MDCO-216 and ETC-216. RESULTS: No inflammatory reaction was observed in HV and sCAD patients following MDCO-216 treatment, judging by body temperature, white cell counts, neutrophil counts, C-reactive protein, circulating cytokines (IL-6, TNF-α), and adverse events. In the ex vivo experiment, the geometric means (SD) of the ratio of MDCO-216 stimulated IL-6 over background levels were 0.8 (1.9), 0.7 (1.5), 1.0 (2.0) for respectively HV, sCAD, aCAD. The corresponding ETC-216 stimulated values were 15.8 (2.9), 9.5 (3.6), 3.8 (4.0). TNF-α results were comparable. Because many ETC-216 stimulated samples had cytokine concentrations >ULOQ, ratios were categorised and marginal homogeneity of the contingency table (MDCO-216 versus ETC-216) was assessed with the Stuart-Maxwell test. P-values were ≤0.0005 for all populations. CONCLUSIONS: MDCO-216 did not induce adverse immunostimulation in HV and sCAD patients, in contrast to ETC-216. Results from the ex vivo stimulation suggests the same holds true for aCAD patients.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phosphatidylcholines
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Coronary Artery Disease
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Apolipoprotein A-I
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Inflammation
Type of study:
Clinical_trials
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Observational_studies
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Risk_factors_studies
Limits:
Adolescent
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Adult
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Aged
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Aged80
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Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
Cardiovasc Drugs Ther
Journal subject:
ANGIOLOGIA
/
CARDIOLOGIA
/
TERAPIA POR MEDICAMENTOS
Year:
2017
Document type:
Article
Affiliation country:
Netherlands
Country of publication:
United States