So Min Wook, Kim A-Ran, Lee Seung-Geun
Department of Internal Medicine, Pusan National University School of Medicine, Yangsan, Republic of Korea.
Division of Rheumatology, Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea.
Rheumatol Ther. 2024 Aug;11(4):881-895. doi: 10.1007/s40744-024-00674-1. Epub 2024 May 20.
Drug persistence may be a surrogate marker that reflects both long-term efficacy and safety in clinical settings, and tuberculosis (TB) is considered as one of the most important opportunistic infections after the biological treatment in rheumatoid arthritis (RA). We aimed to compare drug persistence and incidence of TB between tumor necrosis factor alpha (TNFα) inhibitors and tocilizumab in patients with RA using data from the Korean Health Insurance Review and Assessment Service database.
In this analysis, 5449 patients with RA who started TNFα inhibitors, such as adalimumab, etanercept, infliximab, and golimumab or tocilizumab, as the first-line biological therapy between January 2014 and December 2017 were analyzed and followed up until December 2019. Drug persistence was defined as the duration from initiation to first discontinuation, and TB was defined as the prescription of > 2 anti-TB medications after the initiation of biologics.
TNFα inhibitors and tocilizumab were prescribed in 4202 (adalimumab, 1413; etanercept, 1100; infliximab, 769; golimumab 920) and 1247 patients with RA, respectively. During the analysis period, 2090 (49.7%) and 477 (38.3%) patients with RA discontinued TNFα inhibitors and tocilizumab, respectively, and 42 patients with RA developed TB (TNFα inhibitors, 33; tocilizumab, 9). After adjustment for confounding factors, TNFα inhibitors were significantly associated with a higher risk of discontinuation compared with tocilizumab (hazard ratio (HR) 1.63, p < 0.001). In subgroup analysis, all types of TNFα inhibitors, except for infliximab, demonstrated a significantly lower persistence rate compared with tocilizumab. There was no significant difference in TB incidence between tocilizumab and TNFα inhibitors. In subgroup analysis, infliximab has a significantly higher risk of TB compared with tocilizumab (HR 2.84, p = 0.02).
In this analysis, tocilizumab had longer persistence than TNFα inhibitors with a similar incidence of TB. Our analysis has limitations: (1) The HIRA database lacks clinical details like disease activity and joint damage extent, potentially influencing the analysis results. (2) Reasons for discontinuing biological agents were not available. (3) TB diagnoses may be inaccurate because of missing microbiological results. (4) We did not analyze the impact of treating latent TB infection on TB development post-biological treatment, despite mandatory screening in Korea.
药物持续性可能是反映临床环境中长期疗效和安全性的替代指标，而结核病（TB）被认为是类风湿关节炎（RA）生物治疗后最重要的机会性感染之一。我们旨在利用韩国健康保险审查和评估服务数据库的数据，比较肿瘤坏死因子α（TNFα）抑制剂和托珠单抗在RA患者中的药物持续性和TB发病率。
在本分析中，对2014年1月至2017年12月期间开始使用TNFα抑制剂（如阿达木单抗、依那西普、英夫利昔单抗和戈利木单抗）或托珠单抗作为一线生物治疗的5449例RA患者进行分析，并随访至2019年12月。药物持续性定义为从开始使用到首次停药的持续时间，TB定义为生物制剂开始使用后开具>2种抗结核药物的处方。
分别有4202例（阿达木单抗1413例、依那西普1100例、英夫利昔单抗769例、戈利木单抗920例）和1247例RA患者使用了TNFα抑制剂和托珠单抗。在分析期间，分别有2090例（49.7%）和477例（38.3%）RA患者停用了TNFα抑制剂和托珠单抗，42例RA患者发生了TB（TNFα抑制剂组33例，托珠单抗组9例）。在调整混杂因素后，与托珠单抗相比，TNFα抑制剂停药风险显著更高（风险比（HR）1.63，p<0.001）。在亚组分析中，除英夫利昔单抗外，所有类型的TNFα抑制剂与托珠单抗相比，持续性率均显著较低。托珠单抗和TNFα抑制剂之间的TB发病率无显著差异。在亚组分析中，英夫利昔单抗与托珠单抗相比，TB风险显著更高（HR 2.84，p=0.02）。
在本分析中，托珠单抗的持续性长于TNFα抑制剂，TB发病率相似。我们的分析存在局限性：（1）HIRA数据库缺乏疾病活动度和关节损伤程度等临床细节，可能影响分析结果。（2）无法获得停用生物制剂的原因。（3）由于微生物学结果缺失，TB诊断可能不准确。（4）尽管韩国进行了强制性筛查，但我们没有分析治疗潜伏性TB感染对生物治疗后TB发生的影响。
