Ingress-Health HWM GmbH, a wholly owned subsidiary of Cytel Inc., Potsdamer Str. 58, 10785 Berlin, Germany.
Amgen GmbH, Riesstraße 24, 80992 München, Germany.
Curr Rheumatol Rev. 2023 Jun 5;19(3):303-313. doi: 10.2174/1573397118666220829123713.
To investigate injection site pain (ISP) and other injection site outcomes caused by biologics administered alongside citrate-free (CF) and citrate-containing (CC) formulations.
Electronic literature databases (Medline, Embase, and Cochrane Library) were systematically searched for clinical trials and observational studies reporting on injection site outcomes after subcutaneous administration of biologics. Studies with unknown excipient formulations were excluded. The primary outcome was ISP, and secondary outcomes included any other reported injection site reactions (ISRs). Meta-analysis approaches were used to aggregate evidence identified via the conducted systematic literature review.
A total of two observational studies, two cross-over/sequential trials, and three head-tohead comparison trials directly comparing CF with CC biologics were identified, as well as seven placebo-controlled trials. Evidence from five of the seven direct comparison studies suggested reduced pain perception at the injection site when CF formulations were applied. Findings for other ISRs were balanced between both formulations, with slightly favorable results for preparations without citrate. A meta-analysis of placebo-controlled trials found no significant difference between arms with CF formulations and placebo regarding the proportion of patients experiencing ISP (OR 0.62, 95% CI 0.30-1.28).
Excipient formulations are rarely specified in studies assessing pain and other ISRs of subcutaneously administered biologics. The available data indicate that subcutaneous administration of biologic agents without citrate may be associated with lower pain perception outcomes compared with treatment using CC formulations. Importantly, ISP is influenced by many factors which may have affected the results. More research is needed to assess how formulation excipients influence ISRs.
研究与无柠檬酸盐（CF）和含柠檬酸盐（CC）制剂一起使用的生物制剂引起的注射部位疼痛（ISP）和其他注射部位结局。
系统检索了 Medline、Embase 和 Cochrane 图书馆中的电子文献数据库，以寻找报告皮下给予生物制剂后注射部位结局的临床试验和观察性研究。排除了未知赋形剂配方的研究。主要结局是 ISP，次要结局包括任何其他报告的注射部位反应（ISR）。使用荟萃分析方法对通过进行的系统文献综述确定的证据进行汇总。
共确定了两项观察性研究、两项交叉/序贯试验和三项直接比较 CF 与 CC 生物制剂的头对头比较试验，以及七项安慰剂对照试验。来自七项直接比较研究中的五项的证据表明，应用 CF 制剂时，注射部位的疼痛感知降低。两种制剂之间的其他 ISR 结果平衡，无柠檬酸制剂的结果略有优势。对安慰剂对照试验的荟萃分析发现，CF 制剂组与安慰剂组在经历 ISP 的患者比例方面无显着差异（OR 0.62，95% CI 0.30-1.28）。
在评估皮下给予生物制剂的疼痛和其他 ISR 的研究中，赋形剂配方很少指定。现有数据表明，与使用 CC 制剂相比，皮下给予不含柠檬酸盐的生物制剂可能与较低的疼痛感知结局相关。重要的是，ISP 受许多可能影响结果的因素影响。需要进一步研究来评估制剂赋形剂如何影响 ISR。
