Filgrastim, a biopharmaceutical listed on WHO model list of essential medicines, was approved in USA in 1991 for patients with non-myeloid malignancies associated with severe neutropenia and fever. Several filgrastim biosimilars have now been approved in USA, Europe and elsewhere since 2008, based on the reference product which has lost patent exclusivity; however their immunogenicity and safety is controversial. We conducted a retrospective, post market study between 1991 and May 2018 using VigiBase®. The study included all adverse events with case reports ≥150. Overall, 11,183 adverse drugs reaction reports were identified during observation period; of which 5764; 51.5% reports concerned to Neupogen®, the originator, and rest consists of Leucostim® (N = 680), Zarzio® (N = 622), Grasin® (N = 545), Nivestim® (N = 359) and Tevagrastim® (N = 152) biosimilars. When compared with the originator, Grasin® was associated with higher reporting of pyrexia (11.5% vs 7.9%, ROR 1.52, IC₀₂₅ 1.12), myalgia (37% vs 2.2%, ROR 25.94, IC₀₂₅ 2.11) and back pain (11.3% vs 4%, ROR 3.09, IC₀₂₅ 2.32). Zarzio® was associated with increased reporting of arthralgia (4.5% vs 2.9%, ROR 1.59, IC₀₂₅ 1.25) and neutropenia (11.4% vs 4%, ROR 2.59, IC₀₂₅ 3.07). Bone pain was reported more often with Nivestim® (14.4% vs 8.3%, ROR 1.87, IC₀₂₅ 5.30). Drug ineffectiveness was reported in cases with Zarzio® (35.9%), Nivestim® (19.4%) and Tevagrastim® (42.2%). Authors observed significant differences among originator and biosimilars in particular to efficacy, adverse events reported and time to onset of occurrences. Large epidemiologic studies are needed to further confirm these finding and provide additional insights.

Filgrastim是世界卫生组织基本药物标准清单中列出的生物药物，于1991年在美国被批准用于患有严重中性粒细胞减少和发烧相关的非髓样恶性肿瘤的患者。自2008年以来，基于已失去专利独占性的参考产品，几种非格司亭生物仿制药已在美国，欧洲和其他地区得到批准。但是它们的免疫原性和安全性是有争议的。我们在1991年至2018年5月之间使用VigiBase®进行了回顾性的上市后研究。该研究包括病例报告≥150的所有不良事件。观察期间共鉴定出11,183例药品不良反应报告。其中5764; 涉及发起人Neupogen®的51.5％的报告，其余的包括Leucostim®（N  = 680），Zarzio®（N = 622），Grasin®（Ñ  = 545），Nivestim®（Ñ  = 359）和Tevagrastim®（Ñ  = 152）生物仿制药。与原始人相比，Grasin®与发热相关的报道较高（11.5％vs 7.9％，ROR 1.52，IC ₀₂₅ 1.12），肌痛（37％vs 2.2％，ROR 25.94，IC ₀₂₅ 2.11）和背痛（11.3） ％vs 4％，ROR 3.09，IC ₀₂₅ 2.32）。Zarzio®与关节痛（4.5％vs 2.9％，ROR 1.59，IC ₀₂₅ 1.25）和中性粒细胞减少症（11.4％vs 4％，ROR 2.59，IC ₀₂₅ 3.07）的报告增多相关。Nivestim®报告的骨痛发生率更高（14.4％比8.3％，ROR 1.87，IC ₀₂₅5.30）。在Zarzio®（35.9％），Nivestim®（19.4％）和Tevagrastim®（42.2％）的病例中报告了药物无效。作者观察到原始药物和生物仿制药之间存在显着差异，尤其是在功效，报道的不良事件和发作时间方面。需要进行大规模的流行病学研究，以进一步确认这些发现并提供更多的见解。