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Janus 激酶(JAK)抑制剂在类风湿关节炎中的持久性:澳大利亚全国性研究。

Persistence of Janus-kinase (JAK) inhibitors in rheumatoid arthritis: Australia wide study.

机构信息

Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.

Prospection, Sydney, NSW, Australia.

出版信息

Semin Arthritis Rheum. 2024 Feb;64:152314. doi: 10.1016/j.semarthrit.2023.152314. Epub 2023 Nov 24.

Abstract

BACKGROUND

To compare persistence of disease-modifying antirheumatic (DMARDs), with a focus on Janus kinase (JAK) inhibitors in Australian rheumatoid arthritis (RA) patients.

METHODS

A retrospective observational study was conducted among 4,521 RA patients (females n=3,181 [70.4%]), using data from the Services Australia 10% Pharmaceuticals Benefits Scheme (PBS) dataset, aged ≥18 years and initiating a DMARD between 2011 to 2021. Kaplan-Meier analysis was used to estimate persistence rates, defined as occurrence of 6 months gap after the end of a drug dispensing.

RESULTS

Twelve-month persistence rates were 72% for upadacitinib, 61% for baricitinib, 58% for subcutaneous tumor necrosis factor-alpha inhibitors (TNFi), 55% for tocilizumab, 53% for tofacitinib, and 49% for abatacept. Median treatment persistence was not reached for upadacitinib (n=574) and baricitinib (n=553); and was 15.0 months for tofacitinib (95% CI 13.5-19.5), 20.5 months for TNFi (95% CI 19.0-22.4), 19.1 months for tocilizumab (95% CI 17.9-23.6), and 12.5 months for abatacept (95% CI 10.4-14.9). Persistence rates on first-line JAK inhibitors were 68% for upadacitinib and baricitinib and 55% for tofacitinib, and 49% for TNFi, 55% for abatacept, and 57% for tocilizumab; rates were sustained for upadacitinib, TNFi, and tocilizumab but dropped to 59% for baricitinib and 47% for abatacept in the second-line treatment. For each b/tsDMARD, persistence rates were higher when combined with methotrexate or other conventional synthetic DMARDs. The median oral glucocorticoid dose decreased from 4.3 mg/day (range:0-40) to 2.3 mg/day (range:0-22) over 2 years. Changes were significant for all RA DMARDs, tofacitinib and baricitinib combined (1-2 years post initiation only), TNFi, abatacept, and tocilizumab.

CONCLUSIONS

In a real-world setting, we showed highest persistence rates on upadacitinib, followed by baricitinib and then TNFi therapy and was improved by co-therapy. All agents appeared to be corticosteroid sparing.

摘要

背景

比较疾病修饰抗风湿药物(DMARDs)的持久性,重点是澳大利亚类风湿关节炎(RA)患者的 Janus 激酶(JAK)抑制剂。

方法

使用来自澳大利亚服务部 10%药品福利计划(PBS)数据集的数据,对 4521 名年龄≥18 岁并在 2011 年至 2021 年间开始使用 DMARD 的 RA 患者(女性 n=3181[70.4%])进行了回顾性观察性研究。使用 Kaplan-Meier 分析来估计持久性率,定义为在药物配药结束后出现 6 个月的差距。

结果

乌帕达替尼的 12 个月持续率为 72%,巴利昔替尼为 61%,皮下肿瘤坏死因子-α抑制剂(TNFi)为 58%,托珠单抗为 55%,托法替尼为 53%,阿巴西普为 49%。乌帕达替尼(n=574)和巴利昔替尼(n=553)未达到中位治疗持续时间;托法替尼为 15.0 个月(95%CI 13.5-19.5),TNFi 为 20.5 个月(95%CI 19.0-22.4),托珠单抗为 19.1 个月(95%CI 17.9-23.6),阿巴西普为 12.5 个月(95%CI 10.4-14.9)。一线 JAK 抑制剂的持续率为乌帕达替尼和巴利昔替尼为 68%,托法替尼为 55%,TNFi 为 49%,阿巴西普为 55%,托珠单抗为 57%;乌帕达替尼、TNFi 和托珠单抗的持续率保持稳定,但二线治疗中巴利昔替尼和阿巴西普的持续率分别降至 59%和 47%。对于每种 b/tsDMARD,与甲氨蝶呤或其他常规合成 DMARD 联合使用时,持续率更高。口服糖皮质激素剂量中位数从 4.3mg/天(范围:0-40)降至 2.3mg/天(范围:0-22),持续 2 年。所有 RA DMARD、托法替尼和巴利昔替尼联合治疗(仅在开始后 1-2 年)、TNFi、阿巴西普和托珠单抗的变化均具有统计学意义。

结论

在真实环境中,我们发现乌帕达替尼的持续率最高,其次是巴利昔替尼,然后是 TNFi 治疗,联合治疗可改善持续率。所有药物似乎都有皮质类固醇节约作用。

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