Department of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Department of Medicine, McGill University, Montreal, Quebec, Canada; Division of Rheumatology, Jewish General Hospital, Montreal, Quebec, Canada; Lady Davis Institute of Medical Research, Montreal, Quebec, Canada.
Respir Med. 2021 Aug-Sep;185:106482. doi: 10.1016/j.rmed.2021.106482. Epub 2021 May 27.
Although interstitial lung disease (ILD) occurs in over half of systemic sclerosis (SSc) patients and represents a leading cause of mortality, there are currently no preventative strategies. We evaluated if gastroprotective agents were associated with a lower incident risk of SSc-ILD.
An SSc cohort without clinically apparent ILD at baseline was constructed from the Canadian Scleroderma Research Group registry. The primary exposure was any use of gastroprotective agents. Treatment with promotility agents was assessed as a secondary exposure. Time to development of clinically apparent ILD was compared between exposed and unexposed person-time, using a multivariable marginal structural Cox model incorporating inverse probability of treatment weights to address time-varying confounding.
In total, 798 subjects met inclusion criteria. At cohort entry, median disease duration was 7.6 (IQR 3.9-15.6) years. During a median 4.4 (IQR 2.6-7.2) years of follow-up, 158 new ILD cases were diagnosed, for a crude incidence of 4.4 (95% CI 3.8-5.1) events per 100 person-years. Most (2085, 73.4%) person-visits were exposed to gastroprotective agents, 579 (20.4%) were exposed to promotility agents, and 554 (19.5%) were exposed to both agents. The marginal structural weighted hazard ratio (HR) for incident ILD related to gastroprotective agents was 0.86 (95% CI 0.52-1.41). When exposure was defined as treatment with promotility agents, the weighted adjusted HR was 0.79 (95% CI: 0.35-1.77).
In this large retrospective cohort study, we were unable to demonstrate a protective role for gastroprotective and promotility agents in preventing clinically apparent SSc-ILD.
尽管间质性肺病（ILD）在超过半数的系统性硬化症（SSc）患者中发生，并且是导致死亡的主要原因，但目前尚无预防策略。我们评估了胃保护剂是否与较低的 SSc-ILD 发病风险相关。
从加拿大硬皮病研究组登记处构建了一个基线时无临床明显 ILD 的 SSc 队列。主要暴露因素是使用任何胃保护剂。将促动力药物的治疗作为次要暴露因素进行评估。使用多变量边际结构 Cox 模型比较暴露和未暴露的个体时间发生临床明显 ILD 的时间，并使用逆概率治疗权重来解决随时间变化的混杂因素。
共有 798 名患者符合纳入标准。在队列入组时，中位疾病持续时间为 7.6（IQR 3.9-15.6）年。在中位 4.4（IQR 2.6-7.2）年的随访期间，诊断出 158 例新的 ILD 病例，粗发病率为每 100 人年 4.4（95%CI 3.8-5.1）例。大多数（2085 例，73.4%）人就诊时暴露于胃保护剂，579 例（20.4%）暴露于促动力剂，554 例（19.5%）同时暴露于两种药物。与胃保护剂相关的新发 ILD 的边际结构加权风险比（HR）为 0.86（95%CI 0.52-1.41）。当将暴露定义为使用促动力药物治疗时，加权调整后的 HR 为 0.79（95%CI：0.35-1.77）。
在这项大型回顾性队列研究中，我们未能证明胃保护剂和促动力剂在预防临床明显的 SSc-ILD 方面具有保护作用。
