Sota Jurgen, Insalaco Antonella, Cimaz Rolando, Alessio Maria, Cattalini Marco, Gallizzi Romina, Maggio Maria Cristina, Lopalco Giuseppe, La Torre Francesco, Fabiani Claudia, Pardeo Manuela, Olivieri Alma Nunzia, Sfriso Paolo, Salvarani Carlo, Gaggiano Carla, Grosso Salvatore, Bracaglia Claudia, De Benedetti Fabrizio, Rigante Donato, Cantarini Luca
Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy.
Division of Rheumatology, Department of Pediatric Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Front Pharmacol. 2019 Jan 8;9:1526. doi: 10.3389/fphar.2018.01526. eCollection 2018.
Few studies have reported the drug retention rate (DRR) of biologic drugs in juvenile idiopathic arthritis (JIA), and none of them has specifically investigated the DRR of interleukin (IL)-1 inhibitors on systemic JIA (sJIA). This study aims to describe IL-1 inhibitors DRR and evaluate predictive factors of drug survival based on data from a real-world setting concerning sJIA. Medical records from sJIA patients treated with anakinra (ANA) and canakinumab (CAN) were retrospectively analyzed from 15 Italian tertiary referral centers. Seventy seven patients were enrolled for a total of 86 treatment courses. The cumulative retention rate of the IL-1 inhibitors at 12-, 24-, 48-, and 60-months of follow-up was 79.9, 59.5, 53.5, and 53.5%, respectively, without any statistically significant differences between ANA and CAN ( = 0.056), and between patients treated in monotherapy compared to the subgroup co-administered with conventional immunosuppressors ( = 0.058). On the contrary, significant differences were found between biologic-naive patients and those previously treated with biologic drugs ( = 0.038) and when distinguishing according to adverse events (AEs) occurrence ( = 0.04). In regression analysis, patients pre-treated with other biologics (HR = 3.357 [CI: 1.341-8.406], = 0.01) and those experiencing AEs (HR = 2.970 [CI: 1.186-7.435], = 0.020) were associated with a higher hazard ratio of IL-1 inhibitors withdrawal. The mean treatment delay was significantly higher among patients discontinuing IL-1 inhibitors ( = 0.0002). Our findings suggest an excellent overall DRR for both ANA and CAN that might be further augmented by paying attention to AEs and employing these agents as first-line biologics in an early disease phase.
很少有研究报告生物药物在幼年特发性关节炎（JIA）中的药物保留率（DRR），而且没有一项研究专门调查过白细胞介素（IL）-1抑制剂治疗全身型JIA（sJIA）的DRR。本研究旨在基于来自sJIA真实世界的数据描述IL-1抑制剂的DRR，并评估药物留存的预测因素。对来自15个意大利三级转诊中心接受阿那白滞素（ANA）和卡那单抗（CAN）治疗的sJIA患者的病历进行了回顾性分析。共纳入77例患者，总计86个治疗疗程。在随访12个月、24个月、48个月和60个月时，IL-1抑制剂的累积保留率分别为79.9%、59.5%、53.5%和53.5%，ANA和CAN之间（P = 0.056）以及单药治疗患者与联合使用传统免疫抑制剂的亚组之间（P = 0.058）无任何统计学显著差异。相反，在初用生物制剂的患者与先前接受过生物药物治疗的患者之间（P = 0.038）以及根据不良事件（AE）发生情况进行区分时（P = 0.04）发现了显著差异。在回归分析中，先前接受过其他生物制剂治疗的患者（HR = 3.357 [CI：1.341 - 8.406]，P = 0.01）和发生AE的患者（HR = 2.970 [CI：1.186 - 7.435]，P = 0.020）与IL-1抑制剂停药的较高风险比相关。停用IL-1抑制剂的患者平均治疗延迟显著更高（P = 0.0002）。我们的研究结果表明，ANA和CAN总体DRR均良好，通过关注AE并在疾病早期将这些药物用作一线生物制剂，DRR可能会进一步提高。
