Anakinra is a recombinant human interleukin-1 receptor antagonist approved for the treatment of inflammatory diseases. Kineret is avail-able as a solution prepared in a borosilicate glass syringe. For imple-menting a placebo-controlled double-blind randomized clinical trial, anakinra is commonly transferred into plastic syringes. However, there is limited data on anakinra's stability in polycarbonate syringes. We described the results of our previous studies on the use of ana-kinra in glass (VCUART3) versus plastic syringes (VCUART2) com-pared with placebo. These studies were conducted in patients with ST-segment elevation myocardial infarction (STEMI), and we as-sessed the anti-inflammatory effects of anakinra versus placebo by comparing the area under the curve for high-sensitivity cardiac reac-tive protein (AUC-CRP) levels during the first 14 days of STEMI, its clinical effects on heart failure (HF) hospitalization, cardiovascular death, or new diagnosis of HF as well as adverse events profile be-tween groups. The levels of AUC-CRP were 75 (50-255 mg & BULL;day/l) for anakinra in plastic syringes versus 255 (116-592 mg & BULL;day/l) in placebo and 60 (24-139 mg & BULL;day/l) and 86 (43-123 mg & BULL;day/l) for anakinra once and twice daily in glass syringes, respectively, compared with placebo 214 (131-394 mg & BULL;day/l). The rate of adverse events was also comparable between groups. There were no differences in the rate of HF hospitalization or cardiovascular death in patients who re-ceived anakinra in plastic or glass syringes. Fewer cases of new-onset heart failure occurred in patients receiving anakinra in plastic or glass syringes compared with placebo. Anakinra stored in plastic (polycarbonate) syringes provides comparable biologic and clinical effect to glass (borosilicate) syringes.SIGNIFICANCE STATEMENTAnakinra (Kineret) 100 mg administered subcutaneously in pa-tients with ST-segment elevation myocardial infarction (STEMI) for a duration of up to 14 days appears to have comparable safety and biological efficacy signals when delivered in prefilled glass or transferred into plastic polycarbonate syringes. This may have important implications for the feasibility of designing clinical trials in STEMI and other clinical conditions.
Comparison of Safety and Biological Efficacy of Anakinra (Kineret) Dispensed in Polycarbonate Plastic versus Borosilicate Glass Syringes: A Patient-Level Analysis of VCUART2 and VCUART3 Clinical Trials
Golino, Michele;
2023-01-01
Abstract
Anakinra is a recombinant human interleukin-1 receptor antagonist approved for the treatment of inflammatory diseases. Kineret is avail-able as a solution prepared in a borosilicate glass syringe. For imple-menting a placebo-controlled double-blind randomized clinical trial, anakinra is commonly transferred into plastic syringes. However, there is limited data on anakinra's stability in polycarbonate syringes. We described the results of our previous studies on the use of ana-kinra in glass (VCUART3) versus plastic syringes (VCUART2) com-pared with placebo. These studies were conducted in patients with ST-segment elevation myocardial infarction (STEMI), and we as-sessed the anti-inflammatory effects of anakinra versus placebo by comparing the area under the curve for high-sensitivity cardiac reac-tive protein (AUC-CRP) levels during the first 14 days of STEMI, its clinical effects on heart failure (HF) hospitalization, cardiovascular death, or new diagnosis of HF as well as adverse events profile be-tween groups. The levels of AUC-CRP were 75 (50-255 mg & BULL;day/l) for anakinra in plastic syringes versus 255 (116-592 mg & BULL;day/l) in placebo and 60 (24-139 mg & BULL;day/l) and 86 (43-123 mg & BULL;day/l) for anakinra once and twice daily in glass syringes, respectively, compared with placebo 214 (131-394 mg & BULL;day/l). The rate of adverse events was also comparable between groups. There were no differences in the rate of HF hospitalization or cardiovascular death in patients who re-ceived anakinra in plastic or glass syringes. Fewer cases of new-onset heart failure occurred in patients receiving anakinra in plastic or glass syringes compared with placebo. Anakinra stored in plastic (polycarbonate) syringes provides comparable biologic and clinical effect to glass (borosilicate) syringes.SIGNIFICANCE STATEMENTAnakinra (Kineret) 100 mg administered subcutaneously in pa-tients with ST-segment elevation myocardial infarction (STEMI) for a duration of up to 14 days appears to have comparable safety and biological efficacy signals when delivered in prefilled glass or transferred into plastic polycarbonate syringes. This may have important implications for the feasibility of designing clinical trials in STEMI and other clinical conditions.
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