来氟米特与类风湿肺间质病变

Leflunomide and rheumatoid interstitial lung disease

摘要:

肺间质病变（ILD）是类风湿关节炎（RA）常见的关节外表现之一, 发生率为7.7% , 预后较差, 近年来备受关注。而作为治疗RA的常用药物, 来氟米特引起间质性肺炎的报道逐年增加, 那么, RA合并ILD能否使用来氟米特呢？有文献指出来氟米特可以有效地治疗已经存在肺部疾病（包括甲氨蝶呤导致的间质性肺病）的RA患者, 且未发现药物不良反应及肺部症状加重, 因此指出当出现甲氨蝶呤相关ILD时, 来氟米特可作为替代治疗用药。来氟米特在治疗中国RA患者的安全性是相对较好的, 而近年来国外对于来氟米特引起ILD的报道却屡见不鲜。加拿大从一项治疗RA患者的队列研究中发现, 应用来氟米特治疗的RA患者中ILD发病风险增高（校正RR 1.9）, 但其中无甲氨蝶呤用药史和ILD史的患者经来氟米特治疗后出现ILD的风险并未增高（校正RR 1.2）。日本学者提出对于已有ILD或吸烟、高龄的男性RA患者应禁用或慎用来氟米特。文献报道不同种族RA患者对来氟米特并发的肺部不良反应存在差异, 基因学检测将是寻找答案的关键。总之, 虽然来氟米特有导致ILD的潜在隐患, 但荟萃分析仍提示来氟米特治疗RA有很好的疗效及安全性, 所以, 对于已存在肺部疾患的RA患者, 应分析具体病因慎重应用来氟米特, 并定期监测肺CT。

Abstract:

Interstitial lung disease(ILD) is one of the common extra-articular manifestations of rheumatoid arthritis(RA). Its incidence in RA is 7.7%, and the prognosis is poor. Leflunomide is one of the commonly used drugs for RA, but there are more and more reports about leflunomide caused interstitial pneumonia. Then, should leflunomide be used when RA is complicated with ILD? However, It has been reported that leflunomide can be an effective treatment for RA patient who already sufferred from lung disease [including ILD caused by methotrexate (MTX)], and no adverse drug reaction or pulmonary exacerbation was observed. So, leflunomide could be used as a replacement therapy in patients with MTX related ILD. The safety of leflunomide in treatment of RA was relatively approved in China, but the reports on leflunomide induced ILD were not rare recently outside of China. A cohort study performed in Canada reported that the risk of ILD was increased in RA patients treated with leflunomide (adjusted RR 1.9), but it was not elevated in patients with no previous history of MTX use or ILD(adjusted RR1.2). Japanese scholars proposed that leflunomide application should be prohibited or require careful consideration in elderly male RA patients with history of ILD or smoking. Pulmonary function responsed to leflunomide adversely in an ethnic group dependent manner. Genetics testing might be the key to find the answer. Although leflunomide had a potential risk of causing ILD, meta-analysis indicated satisfactory therapeutic effects and safety of leflunomide for RA. For RA patients with preexisting pulmonary disorders, leflunomide application requires careful consdideration and CT scanning should be monitored regularly.