Bykerk Vivian P, Nash Peter, Nicholls David, Tanaka Yoshiya, Winthrop Kevin, Popova Christina, Tilt Nicola, Haaland Derek
Hospital for Special Surgery, New York, NY, USA.
Griffith University, Queensland, Australia.
Rheumatol Ther. 2023 Jun;10(3):693-706. doi: 10.1007/s40744-023-00541-5. Epub 2023 Feb 27.
There is a paucity of data on how patient characteristics may affect the long-term durability of certolizumab pegol (CZP) in patients with rheumatoid arthritis (RA). This study therefore aimed to investigate CZP durability and reasons for discontinuation over 5 years between different subgroups of patients with RA.
Data were pooled from 27 clinical trials in RA patients. Durability was defined as the percentage of patients randomized to CZP at baseline who were still on CZP treatment at a given timepoint. Post hoc analyses of clinical trial data on CZP durability and reasons for discontinuation among different patient subgroups were conducted using Kaplan-Meier curves and Cox proportional hazards modeling. Patient subgroups included: age (18- < 45/45- < 65/ ≥ 65 years), gender (male/female), prior tumor necrosis factor inhibitor (TNFi) use (yes/no), and disease duration (< 1/1- < 5/5- < 10/ ≥ 10 years).
Among 6927 patients, the durability of CZP was 39.7% at 5 years. Patients aged ≥ 65 years had a 33% greater risk of CZP discontinuation than patients 18- < 45 years (hazard ratio [95% confidence interval]: 1.33 [1.19-1.49]) and patients with prior TNFi use had a 24% greater risk of discontinuing CZP than patients without (1.24 [1.12-1.37]). Conversely, greater durability was observed among patients who had a baseline disease duration of ≥ 1 year. Durability did not differ in the gender subgroup. Of the 6927 patients, the most common reason for discontinuation was inadequate levels of efficacy (13.5%); followed by adverse events (11.9%); consent withdrawn (6.7%); lost to follow-up (1.8%); protocol violation (1.7%); other reasons (9.3%).
CZP durability was comparable with durability data on other bDMARDs in RA patients. Patient characteristics that were associated with greater durability included younger age, TNFi-naïvety, and disease duration ≥ 1 year. Findings may be helpful in informing clinicians on a patient's likelihood of discontinuing CZP, based on their baseline characteristics.
关于类风湿关节炎（RA）患者的特征如何影响赛妥珠单抗聚乙二醇化制剂（CZP）的长期疗效，相关数据较少。因此，本研究旨在调查RA患者不同亚组中CZP的疗效持续性及停药原因，为期5年。
汇总了27项针对RA患者的临床试验数据。疗效持续性定义为基线时随机接受CZP治疗的患者在给定时间点仍接受CZP治疗的百分比。使用Kaplan-Meier曲线和Cox比例风险模型对不同患者亚组中CZP疗效持续性及停药原因的临床试验数据进行事后分析。患者亚组包括：年龄（18至＜45/45至＜65/≥65岁）、性别（男性/女性）、既往是否使用过肿瘤坏死因子抑制剂（TNFi）（是/否）以及病程（＜1/1至＜5/5至＜10/≥10年）。
在6927例患者中，5年时CZP的疗效持续性为39.7%。≥65岁的患者停用CZP的风险比18至＜45岁的患者高33%（风险比[95%置信区间]：1.33[1.19 - 1.49]），既往使用过TNFi的患者停用CZP的风险比未使用过的患者高24%（1.24[1.12 - 1.37]）。相反，基线病程≥1年的患者中观察到更高的疗效持续性。疗效持续性在性别亚组中无差异。在6927例患者中，最常见的停药原因是疗效水平不足（13.5%）；其次是不良事件（11.9%）；撤回同意（6.7%）；失访（1.8%）；违反方案（1.7%）；其他原因（9.3%）。
CZP的疗效持续性与RA患者中其他生物改善病情抗风湿药（bDMARDs）的疗效持续性数据相当。与更高疗效持续性相关的患者特征包括年龄较小、未使用过TNFi以及病程≥1年。这些发现可能有助于临床医生根据患者的基线特征了解其停用CZP的可能性。
