Incidence of Interstitial Lung Disease in Patients With Rheumatoid Arthritis Treated With Biologic and Targeted Synthetic Disease-Modifying Antirheumatic Drugs.
Incidence of Interstitial Lung Disease in Patients With Rheumatoid Arthritis Treated With Biologic and Targeted Synthetic Disease-Modifying Antirheumatic Drugs.
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DOI：
10.1001/jamanetworkopen.2023.3640
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发表时间：
2023-03-01
影响因子：
13.8
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本队列研究评估了类风湿关节炎患者接受生物和靶向合成疾病缓解抗风湿药物治疗后间质性肺病的发生率。类风湿关节炎（RA）患者发生间质性肺病（ILD）的风险是否可通过不同生物制剂或靶向合成疾病缓解抗风湿药物（B/tsDMARD）治疗得到改善？在这项队列研究中，与所有类别的bDMARD相比，在28 559例接受托法替尼治疗的RA患者中观察到ILD发生率降低4，在校正模型中，与接受阿达木单抗治疗的患者相比，接受托法替尼治疗的患者ILD风险降低69%。鉴于接受托法替尼治疗的RA患者ILD风险降低，这些数据表明应考虑未来开展托法替尼预防RA-ILD的前瞻性研究。目前缺乏关于类风湿关节炎（RA）患者使用生物和靶向合成疾病缓解抗风湿药物（B/tsDMARD）发生间质性肺病（ILD）风险的数据。确定接受不同B/tsDMARD治疗的RA患者发生ILD的风险。回顾性队列研究，使用2003年12月至2019年12月Optum Clinformatics Data Mart的索赔数据。纳入了连续入组1年或以上、接受关注的B/tsDMARD治疗且无既存ILD的RA成人患者。数据分析时间为2021年10月至2022年4月。阿达木单抗、阿巴西普、利妥昔单抗、托珠单抗或托法替尼新给药。计算ILD发生的粗发生率（IR）。使用Cox回归模型比较不同B/tsDMARD的ILD风险。一项敏感性分析采用流行的新使用者队列设计，比较了接受托法替尼和阿达木单抗治疗的患者。共有28559例RA患者（平均[SD]年龄55.6 [13.7]岁; 22158例女性[78%]）接受阿达木单抗（13326例患者）、阿巴西普（5676例患者）、利妥昔单抗（5444例患者）、托珠单抗（2548例患者）或托法替尼（1565例患者）治疗。ILD的粗IR/1000人-年为3.43（95% CI 2.85-4.09）阿达木单抗，4.46（95% CI 3.44-5.70），利妥昔单抗6.15（95% CI 4.76-7.84），托珠单抗5.05（95% CI 3.47-7.12），托法替尼1.47（95% CI 0.54-3.27）。经多次校正后，与阿达木单抗治疗患者相比，托法替尼治疗患者的ILD风险较低（校正风险比[aHR] 0.31; 95% CI，0.12-0.78; P = 0.009）。在一项流行的新使用者队列分析中，与阿达木单抗相比，接受托法替尼治疗的患者ILD风险降低68%（aHR 0.32; 95% CI 0.13-0.82; P <0.001）。在校正模型中，与阿达木单抗治疗患者相比，托法替尼治疗患者的ILD风险降低69%。在该RA患者回顾性队列中，与接受所有评估的bDMARD治疗的患者相比，接受托法替尼治疗的患者的ILD发生率最低，调整重要协变量后，与接受阿达木单抗治疗的患者相比，接受托法替尼治疗的患者的ILD风险降低。需要进行额外的前瞻性研究，以更好地了解托法替尼在预防RA患者ILD中的作用。这些结果虽然具有显著性，但鉴于托法替尼组的样本量相当小，应谨慎解释。
This cohort study evaluates the incidence of interstitial lung disease in patients with rheumatoid arthritis who have been treated with biologic and targeted synthetic disease-modifying antirheumatic drugs. Is the risk of developing interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) modified by treatment with different biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs)? In this cohort study,a 4 reduced incidence of ILD was observed in 28 559 patients with RA treated with tofacitinib compared with all classes of bDMARDs, and in an adjusted model, there was a 69% reduced risk of ILD in patients treated with tofacitinib compared with patients treated with adalimumab. Given the reduced risk in ILD among patients with RA treated with tofacitinib, these data suggest future prospective studies with tofacitinib to prevent RA-ILD should be considered. Current data are lacking regarding the risk of biologic and targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) use on the development of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). To determine the risk of developing ILD in patients with RA undergoing treatment with different b/tsDMARDs. Retrospective cohort study using claims data from the Optum Clinformatics Data Mart between December 2003 and December 2019. Adult patients with RA, 1 year or more of continuous enrollment, treatment with a b/tsDMARD of interest, and without preexisting ILD were included. Data were analyzed from October 2021 to April 2022. New administration of adalimumab, abatacept, rituximab, tocilizumab, or tofacitinib. Crude incidence rates (IRs) for the development of ILD were calculated. The risk of ILD across different b/tsDMARDs was compared using Cox-regression models. A sensitivity analysis using a prevalent new-user cohort design compared patients treated with tofacitinib and adalimumab. A total of 28 559 patients with RA (mean [SD] age 55.6 [13.7] years; 22 158 female [78%]) were treated with adalimumab (13 326 patients), abatacept (5676 patients), rituximab (5444 patients), tocilizumab (2548 patients), or tofacitinib (1565 patients). Crude IRs per 1000 person-years for ILD were 3.43 (95% CI 2.85-4.09) for adalimumab, 4.46 (95% CI 3.44-5.70) for abatacept, 6.15 (95% CI 4.76-7.84) for rituximab, 5.05 (95% CI 3.47-7.12) for tocilizumab, and 1.47 (95% CI 0.54-3.27) for tofacitinib. After multiple adjustments, compared with patients treated with adalimumab, patients treated with tofacitinib had a lower risk of ILD (adjusted hazard ratio [aHR] 0.31; 95% CI, 0.12-0.78; P = .009). In a prevalent new-user cohort analysis, patients treated with tofacitinib had 68% reduced risk of ILD compared with adalimumab (aHR 0.32; 95% CI 0.13-0.82; P < .001). In an adjusted model, there was a 69% reduced risk of ILD in patients treated with tofacitinib compared with patients treated with adalimumab. In this retrospective cohort of patients with RA, patients treated with tofacitinib had the lowest incidence of ILD compared with patients treated with all bDMARDs evaluated, and patients treated with tofacitinib had a reduced risk of ILD compared with patients treated with adalimumab after adjusting for important covariates. Additional prospective studies are needed to better understand the role tofacitinib may play in preventing ILD in patients with RA. These results, while significant, should be interpreted with caution given the fairly small sample size of the tofacitinib group.