Abstract

Anakinra is a recombinant human interleukin-1 (IL-1) receptor antagonist approved for the treatment of inflammatory diseases. Kineret® is available as a solution prepared in a borosilicate glass syringe. For implementing 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 anakinra in glass (VCUART3) versus plastic syringes (VCUART2) compared to placebo. These studies were conducted in patients with ST-elevation myocardial infarction (STEMI), and we assessed the anti-inflammatory effects of anakinra versus placebo, by comparing the area-under-the-curve for high-sensitive cardiac reactive 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 between groups. The levels of AUC-CRP were 75 (50-255 mg·day/L) for anakinra in plastic syringes vs 255 (116-592 mg·day/L) in placebo and 60 (24-139 mg·day/L), 86 (43-123 mg·day /L) for anakinra once and twice daily in glass syringes, respectively compared to placebo 214 (131-394 mg·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 received anakinra in plastic or glass syringes. Fewer cases of new-onset heart failure occurred in patients receiving anakinra in plastic or glass syringes compared to placebo. Anakinra stored in plastic (polycarbonate) syringes provides comparable biological and clinical effect to glass (borosilicate) syringes.

Significance Statement Anakinra (Kineret®) 100 mg administered subcutaneously in patients with 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.