Shimizu Hirohito, Kobayashi Hisanori, Kanbori Masayoshi, Ishii Yutaka
Medical Affairs Division, Immunology Department, Janssen Pharmaceutical K.K, Tokyo, Japan.
Clinical Science Division, External Collaboration and Portfolio Management Department, R&D Janssen Pharmaceutical K.K., Tokyo, Japan.
Rheumatol Ther. 2020 Jun;7(2):311-325. doi: 10.1007/s40744-020-00198-4. Epub 2020 Feb 29.
While dose escalation of golimumab has been used for patients with rheumatoid arthritis who demonstrate an inadequate response to the standard dose, its effectiveness has not been fully evaluated. The aim of this study was to assess the clinical outcome observed by dose escalation of golimumab for patients with rheumatoid arthritis in the daily clinical setting.
A post hoc analysis was performed of data from the 24-week post-marketing surveillance conducted in Japan (n = 5154). A total of 301 patients with moderate or high disease activity at baseline who underwent dose escalation of golimumab were assessed for effectiveness at 24 weeks based on several variables, such as DAS28-CRP, SDAI, and CDAI, as well as for medication persistence through 24 weeks. In addition, the study population was stratified by the time to dose escalation, and effectiveness was likewise evaluated. Logistic regression analysis was performed to identify factors associated with a moderate/good EULAR response to golimumab at 24 weeks.
Patients with golimumab dose escalation showed significant improvement of the clinical signs and symptoms of rheumatoid arthritis at 24 weeks, as indicated by reduction of the DAS28-CRP (∆0.89), SDAI (∆8.64), and CDAI (∆8.28) scores. This result was relatively consistent across the subgroups stratified by the timing of dose escalation. According to Kaplan-Meier analysis, 78.1% of the patients continued to receive golimumab at 24 weeks, and this was also similar among the subgroups stratified by the time to dose escalation. Multivariate analysis identified male sex and previous biologic therapy as factors that were significantly associated with the clinical response at 24 weeks.
In real-world clinical practice, improvement of disease activity was observed after uptitration of golimumab from 50 to 100 mg regardless of the timing. Male patients and biologic-naive patients were more likely to respond to dose escalation of golimumab.
UMIN-CTR, Identifier: UMIN000015895.
对于对标准剂量疗效不佳的类风湿关节炎患者，已采用逐步增加戈利木单抗剂量的方法，但尚未对其有效性进行全面评估。本研究旨在评估在日常临床环境中，类风湿关节炎患者逐步增加戈利木单抗剂量后的临床结局。
对在日本进行的为期24周的上市后监测数据（n = 5154）进行事后分析。共有301例基线时疾病活动度为中度或高度且接受戈利木单抗剂量递增的患者，基于几个变量（如DAS28-CRP、SDAI和CDAI）在24周时评估其有效性，并评估24周内的用药持续性。此外，根据剂量递增时间对研究人群进行分层，并同样评估有效性。进行逻辑回归分析以确定与24周时对戈利木单抗产生中度/良好欧洲抗风湿病联盟（EULAR）反应相关的因素。
戈利木单抗剂量递增的患者在24周时类风湿关节炎的临床体征和症状有显著改善，DAS28-CRP（Δ0.89）、SDAI（Δ8.64）和CDAI（Δ8.28）评分降低表明了这一点。该结果在根据剂量递增时间分层的亚组中相对一致。根据Kaplan-Meier分析，78.1%的患者在24周时继续接受戈利木单抗治疗，这在根据剂量递增时间分层的亚组中也相似。多变量分析确定男性性别和既往生物治疗是与24周时临床反应显著相关的因素。
在现实世界的临床实践中，无论时间如何，将戈利木单抗从50 mg滴定至100 mg后疾病活动度均有改善。男性患者和未接受过生物治疗的患者对戈利木单抗剂量递增更可能有反应。
UMIN-CTR，标识符：UMIN000015895。
