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类风湿关节炎相关间质性肺病的抗纤维化药物治疗 - 全国性队列的真实世界数据。

Antifibrotics in rheumatoid arthritis-associated interstitial lung disease - real-world data from a nationwide cohort.

机构信息

Hospital Garcia de Orta, Unidade Local de Saúde Almada-Seixal.

Centro Hospitalar Universitário de São João, Unidade Local de Saúde de São João.

出版信息

ARP Rheumatol. 2024 Jul-Sep;3(3):182-188. doi: 10.63032/POPM9413.

Abstract

INTRODUCTION

Interstitial lung disease (ILD) is the most common pulmonary manifestation of rheumatoid arthritis (RA) and is associated with an increased mortality. Clinical trials have shown that antifibrotics (nintedanib and pirfenidone) can slow the progression of connective tissue disease-associated ILD. This study aims to evaluate the effectiveness and tolerability of antifibrotics in a national, real-world cohort of patients with RA-ILD.

MATERIAL AND METHODS

We conducted an observational multicenter study of RA-ILD patients treated with antifibrotics, who were prospectively followed in Reuma.pt. Demographic and clinical data, pulmonary function tests (PFTs) results and adverse events (AEs) were collected. A linear mixed model with random intercept was used to compare PFT results within 12 (±6) months before to 12 (±6) months after antifibrotic initiation. Drug persistence was evaluated using Kaplan-Meier curves.

RESULTS

We included 40 RA-ILD patients, 27 (67.5%) initially treated with nintedanib and 13 (32.5%) with pirfenidone. Most of the patients were female (55%), and current or past smokers (52.5%). At antifibrotic initiation, mean age was 70.9 ± 7.1 years and median ILD duration 5.0 [IQR 2.3-7.5] years. A total of 20 patients were included in effectiveness analysis, with the use of antifibrotics interrupting the decline of forced vital capacity (FVC; decline 300 ± 500 mL in the year before antifibrotic initiation vs. improvement of 200 ± 400 mL in the year following antifibrotic initiation, p=0.336) and total lung capacity (TLC; decline 800 ± 300 mL in the year before antifibrotic initiation vs. improvement of 600 ± 900 mL in the year following antifibrotic initiation, p=0.147). However, diffusion capacity for carbon monoxide remained in decline (3% decline in the year before antifibrotic initiation vs. 2.9% decline in the year following antifibrotic initiation, p=0.75). AEs were reported in 16 (40%) patients and led to drug discontinuation in 12 (30%). Median duration of drug persistence was 150.3 weeks (95 %CI 11.0-289.6), with no difference between nintedanib and pirfenidone (p = 0.976).

CONCLUSION

This study with real-world data corroborates the usefulness of antifibrotics in stabilizing lung function, based on FVC and TLC. However, AEs were frequently reported and were the main cause for drug discontinuation.

摘要

简介

间质性肺病(ILD)是类风湿关节炎(RA)最常见的肺部表现,与死亡率增加有关。临床试验表明,抗纤维化药物(尼达尼布和吡非尼酮)可减缓结缔组织疾病相关的ILD 的进展。本研究旨在评估抗纤维化药物在 RA-ILD 患者的全国性真实世界队列中的有效性和耐受性。

材料和方法

我们进行了一项观察性多中心研究,纳入了接受抗纤维化药物治疗的 RA-ILD 患者,前瞻性随访于 Reuma.pt。收集人口统计学和临床数据、肺功能测试(PFT)结果和不良事件(AE)。使用具有随机截距的线性混合模型比较抗纤维化药物治疗前 12(±6)个月和治疗后 12(±6)个月的 PFT 结果。使用 Kaplan-Meier 曲线评估药物持续时间。

结果

我们纳入了 40 名 RA-ILD 患者,27 名(67.5%)患者最初接受尼达尼布治疗,13 名(32.5%)患者接受吡非尼酮治疗。大多数患者为女性(55%),且为当前或既往吸烟者(52.5%)。在开始使用抗纤维化药物时,平均年龄为 70.9±7.1 岁,ILD 持续时间中位数为 5.0[IQR 2.3-7.5]年。共有 20 名患者纳入有效性分析,使用抗纤维化药物可阻止用力肺活量(FVC)下降(抗纤维化药物治疗前一年下降 300±500mL,治疗后一年改善 200±400mL,p=0.336)和总肺容量(TLC)下降(抗纤维化药物治疗前一年下降 800±300mL,治疗后一年改善 600±900mL,p=0.147)。然而,一氧化碳弥散量仍呈下降趋势(抗纤维化药物治疗前一年下降 3%,治疗后一年下降 2.9%,p=0.75)。16 名(40%)患者出现 AE,并导致 12 名(30%)患者停药。药物持续时间的中位数为 150.3 周(95%CI 11.0-289.6),尼达尼布和吡非尼酮之间无差异(p=0.976)。

结论

这项基于真实世界数据的研究证实了抗纤维化药物在稳定 FVC 和 TLC 方面对肺功能的有益作用。然而,AE 频繁发生,是导致药物停药的主要原因。

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