Addenbrooke's Hospital, CUHNHSFT, Cambridge CB2 2QQ, UK.
Rheumatology (Oxford). 2011 Dec;50(12):2297-305. doi: 10.1093/rheumatology/ker289. Epub 2011 Oct 22.
Lung disease is commonly encountered in rheumatological practice either as a manifestation of the underlying condition or as a consequence of using disease-modifying therapies. This has been particularly apparent with the TNF-α antagonists and exacerbations of interstitial lung disease (ILD). In view of this, we undertook a review of the current literature to identify non-infectious pulmonary complications associated with the newer biologic agents used for the treatment of rheumatic conditions.
A systematic literature review (SLR) was conducted using PubMed, the Cochrane Library and EMBASE for reviews, meta-analyses, clinical studies and randomized controlled trials, case studies and series, published up to June 2010 using the terms rituximab (RTX), certolizumab, golimumab (GOL), tocilizumab (TCZ) and abatacept in the advanced search option without limitations. In addition, abstracts from International Rheumatology conferences and unpublished data from the Food and Drug Administration, the European Medicines Agency and drug manufacturers were used to complement our search. References were reviewed manually and only those articles that suggested a potential relationship between the biological agent and lung toxicity, following exclusion of other causes, were included.
Reported non-infectious pulmonary adverse events with TCZ included a fatal exacerbation of RA-associated ILD, new-onset ILD, idiopathic pulmonary fibrosis and allergic pneumonitis, as well as three cases of microbiological culture-negative pneumonia. Although RTX had a higher incidence of pulmonary toxicity, only 7 of the 121 cases reported involved rheumatological diseases. GOL treatment was associated with four cases of non-infectious pulmonary toxicity and two cases of pneumonia with negative microbiological studies. There were no episodes of pulmonary toxicity identified for either certolizumab or abatacept.
Our results highlight an association between the use of newer biologic agents (TCZ, RTX and GOL) and the development of non-infectious parenchymal lung disease in patients with RA. Post-marketing surveillance and biologic registries will be critical for detecting further cases of ILD and improving our understanding of the pathophysiology of this process. As the use of these drugs increases, clinicians must remain vigilant for potential pulmonary complications and exercise caution in prescribing biologic therapies, particularly to rheumatological patients with pre-existing ILD.
肺部疾病在风湿病学实践中很常见，无论是作为潜在疾病的表现，还是作为改变疾病治疗的结果。这在 TNF-α 拮抗剂和间质性肺病（ILD）恶化中尤为明显。鉴于此，我们对当前文献进行了综述，以确定与治疗风湿性疾病的新型生物制剂相关的非传染性肺部并发症。
使用 PubMed、Cochrane 图书馆和 EMBASE 进行系统文献综述（SLR），用于综述、荟萃分析、临床研究和随机对照试验、病例研究和系列研究，检索词为利妥昔单抗（RTX）、certolizumab、戈利木单抗（GOL）、托珠单抗（TCZ）和阿巴西普，使用高级搜索选项，无限制地检索截至 2010 年 6 月的文献。此外，还使用国际风湿病会议的摘要和食品药品监督管理局、欧洲药品管理局和药品制造商的未发表数据来补充我们的检索。手动审查参考文献，仅包括那些在排除其他原因后表明生物制剂与肺毒性之间存在潜在关系的文章。
TCZ 报告的非传染性肺部不良事件包括 RA 相关 ILD 的致命恶化、新发 ILD、特发性肺纤维化和过敏性肺炎，以及三例微生物培养阴性肺炎。尽管 RTX 肺部毒性发生率较高，但报告的 121 例病例中仅有 7 例涉及风湿病。GOL 治疗与 4 例非传染性肺部毒性和 2 例微生物研究阴性肺炎有关。certolizumab 或 abatacept 均未发生肺部毒性。
我们的结果强调了新型生物制剂（TCZ、RTX 和 GOL）的使用与 RA 患者非传染性实质肺疾病的发展之间存在关联。上市后监测和生物登记将对检测进一步的 ILD 病例和提高我们对这一过程病理生理学的理解至关重要。随着这些药物的使用增加，临床医生必须警惕潜在的肺部并发症，并在开具生物治疗时谨慎行事，特别是对于患有预先存在的 ILD 的风湿性患者。
