Nash Peter, Vanhoof Johan, Hall Stephen, Arulmani Udayasankar, Tarzynski-Potempa Rita, Unnebrink Kristina, Payne Andrew N, Cividino Alfred
Department of Medicine, University of Queensland Rheumatology Research Unit Sunshine Coast, Queensland, Australia.
Department of Rheumatology, ReumaClinic Genk, Genk, Belgium.
Rheumatol Ther. 2016 Dec;3(2):257-270. doi: 10.1007/s40744-016-0041-3. Epub 2016 Aug 18.
Adalimumab, an anti-tumor necrosis factor antibody, is currently available in a 40 mg/0.8 mL formulation. The objective of this analysis was to evaluate injection site-related pain, safety, and tolerability of a 40 mg/0.4 mL formulation of adalimumab that had fewer excipients, a smaller volume, and a delivery presentation with a smaller gauge needle, versus the current 40 mg/0.8 mL formulation in patients with rheumatoid arthritis (RA).
Two identically designed, phase 2, randomized, single-blind, two-period crossover studies were conducted in Belgium and the Czech Republic (Study 1) and Australia, Canada, and Germany (Study 2). In both studies, adults with RA [biologic-naive or current users of 40 mg/0.8 mL adalimumab with an average injection site-related pain rating ≥3 cm on a visual analog scale (VAS; 0-10 cm)] were randomized to receive 40 mg/0.8 mL or 40 mg/0.4 mL adalimumab at visit 1. After 1-2 weeks (depending on patient medication schedule), patients received the other formulation at visit 2. A pain VAS [McGill Pain Questionnaire (MPQ-SF)] and the Draize scale were evaluated immediately after injection and 15 min postinjection. The primary endpoint was immediate pain after injection.
64 and 61 patients were randomized in Studies 1 and 2, respectively. Both studies found a clinically relevant and statistically significant lower immediate pain after injection for the 40 mg/0.4 mL versus the 40 mg/0.8 mL formulation. The mean difference on the VAS for the pooled data (-2.48 cm) was also clinically relevant. Most other endpoints in both studies favored the 40 mg/0.4 mL formulation, and its tolerability and safety profile were consistent with 40 mg/0.8 mL adalimumab.
A 40 mg/0.4 mL adalimumab formulation was well tolerated and associated with less injection site-related pain than the 40 mg/0.8 mL adalimumab formulation.
ClinicalTrials.gov identifier, NCT01561313 and NCT01502423.
AbbVie.
阿达木单抗是一种抗肿瘤坏死因子抗体，目前有40毫克/0.8毫升的制剂。本分析的目的是评估与目前40毫克/0.8毫升制剂相比，一种辅料更少、体积更小且采用更细规格针头给药的40毫克/0.4毫升阿达木单抗制剂在类风湿关节炎（RA）患者中的注射部位相关疼痛、安全性和耐受性。
在比利时和捷克共和国进行了两项设计相同的2期随机单盲两阶段交叉研究（研究1），在澳大利亚、加拿大和德国进行了另一项研究（研究2）。在两项研究中，将RA成人患者[未使用过生物制剂或当前使用40毫克/0.8毫升阿达木单抗且视觉模拟量表（VAS；0 - 10厘米）上平均注射部位相关疼痛评分≥3厘米]随机分为在第1次就诊时接受40毫克/0.8毫升或40毫克/0.4毫升阿达木单抗。1 - 2周后（取决于患者用药时间表），患者在第2次就诊时接受另一种制剂。在注射后立即和注射后15分钟评估疼痛VAS[麦吉尔疼痛问卷（MPQ - SF）]和德赖兹量表。主要终点是注射后的即时疼痛。
研究1和研究2分别有64例和61例患者被随机分组。两项研究均发现，与40毫克/0.8毫升制剂相比，40毫克/0.4毫升制剂注射后的即时疼痛在临床和统计学上均显著降低。汇总数据的VAS平均差异（-2.48厘米）在临床上也具有相关性。两项研究中的大多数其他终点均有利于40毫克/0.4毫升制剂，其耐受性和安全性与40毫克/0.8毫升阿达木单抗一致。
40毫克/0.4毫升阿达木单抗制剂耐受性良好，与40毫克/0.8毫升阿达木单抗制剂相比，注射部位相关疼痛更少。
ClinicalTrials.gov标识符，NCT01561313和NCT01502423。
艾伯维公司。
