<p>Effect of tumor necrosis factor inhibitors on interstitial lung disease in rheumatoid arthritis: angel or demon?</p>

Abstract

Objectives: This study evaluated the correlation between tumor necrosis factor alpha inhibitor (TNF-I) and interstitial lung disease (ILD) in rheumatoid arthritis (RA). We aimed to raise awareness and consummate therapy by summarizing the characteristics of the adverse events of ILD. Methods: A comprehensive search of the PubMed, Embase, Ovid, Cochrane, China National Knowledge Infrastructure, and Wanfang databases was performed from inception to November 2018. Statistical analysis of demographic characteristics, clinical features, and relative risks was performed using Microsoft Excel 2007 and SPSS version 20.0. Results: A total of 7 eligible articles and another 28 case reports were enrolled. The 7 cohort studies demonstrated the tendency that ILD cases might not benefit from TNF-I therapy. TNF-I might be associated with ILD adverse events. The case reports further confirmed these findings, as most (87.5%) of the cases showed that TNF-1 was harmful to patients with ILD and even resulted in a 35% mortality rate. Further investigation revealed that ILD adverse events tended to appear in female patients with a long RA history ( p <0.05). The subgroup analysis suggested that early detection and precise treatment are key factors in determining survival or death when an ILD adverse event occurs. A large proportion of ILD adverse events (48.6%) appeared at 2.38±1.03 weeks after the infusion of infliximab. Conclusion: A fresh look at the evidence highlights that TNF-I might be associated with ILD adverse events in RA, which can induce more severe pulmonary symptoms and even result in death. Therefore, more attention should be paid to effective prevention, early diagnosis, and precise management. Notably, further prospective cohort studies are warranted to better interpret the association or causality between TNF-I and ILD.

Methotrexate-Associated Pneumonitis and Rheumatoid Arthritis-Interstitial Lung Disease: Current Concepts for the Diagnosis and Treatment

“…Despite previous concerns over potential pulmonary toxicity with leflunomide, this agent also appears to be potentially beneficial for RA-ILD (62). In the setting of RA-ILD, the choice of biological therapy is not clear: A recent review of the literature identified seven studies and 28 case reports, which showed an increased mortality with the use of tumor necrosis factor-inhibitors (TNF-i) (63). In this analysis, female sex and longer disease duration were associated with ILD onset or worsening (63).…”

“…In the setting of RA-ILD, the choice of biological therapy is not clear: A recent review of the literature identified seven studies and 28 case reports, which showed an increased mortality with the use of tumor necrosis factor-inhibitors (TNF-i) (63). In this analysis, female sex and longer disease duration were associated with ILD onset or worsening (63). The heterogeneity in the reported outcome measures was too large to draw any firm conclusions.…”

Adverse effects of biologic anti-inflammatory agents on the respiratory system: A review

“…[23] According to data obtained from the British Society of Rheumatology Biologics Register, the mortality rate from ILD in patients with rheumatoid arthritis (RA) treated with TNF-α inhibitors was similar to those treated with conventional DMARDs. [22] A recent review by Huang et al [24] highlighted that the use of TNF-α inhibitors in patients known to have RA-associated ILD may predispose them to more severe symptoms and even death. [24] While TNF-α inhibition has been used successfully to treat noninfectious granulomatous diseases, paradoxically TNF-α antagonism has also been associated with the development of a granulomatous, sarcoid-like disease, which may have both pulmonary and extra-pulmonary effects.…”

Immunmodulation bei autoimmunen interstitiellen Lungenerkrankungen

“…Adalimumab wird subkutan verabreicht, die übliche Dosis beträgt 40 mg pro Woche. Die Rolle der TNF-α-Blockade bei anderen Autoimmun-ILD ist noch ungeklärt, doch eine aktuelle Übersichtsarbeit zur TNF-α-Blockade bei RA-ILD ergab eine hohe Rate von Nebenwirkungsmeldungen (87,5%) und eine berichtete Mortalität von 35% bei geringer Evidenz von potenziellem Nutzen in dieser Patientenkohorte, da es keine RCT gibt [102].…”