Tumor Necrosis Factor Inhibitors and Lung Disease: A Paradox of Efficacy and Risk

Objective

Tumor necrosis factor inhibitors (TNFi) are being increasingly used for a wide range of indications. There are increasing reports of pulmonary toxicity related to the use of TNFi. In this review, we have attempted to synthesize the available literature regarding noninfectious complications related to TNFi use.

Methods

We reviewed case reports, case series, and clinical trials accessed from the PubMed database (www.pubmed.gov), European League Against Rheumatism web archive (http://www.abstracts2view.com/eular/index.php), and the British Society of Rheumatology Biologics Register Newsletter website (http://www.rheumatology.org.uk/publications) using 23 search terms.

Results

There are increasing data available about use of TNFi in treatment of systemic inflammatory rheumatologic disorders and their attempted use for various pulmonary indications. Currently reported noninfectious pulmonary complications related to TNFi use include most commonly granulomatous disease and pulmonary fibrosis/interstitial lung disease and rarely alveolar hemorrhage and antisynthetase syndrome. De novo granulomatous disease seems to be mostly reversible, whereas pulmonary fibrosis carries the worst prognosis especially in the setting of prior lung fibrosis.

Conclusions

Serious and potentially fatal pulmonary toxicity has been reported during the use of TNFi, specifically from pulmonary fibrosis. Increased awareness during trial design and increased postmarketing surveillance is needed to provide more information about the epidemiology of these complications. Early recognition of these complications may help avert therapeutic misadventures.

Keywords: tumor necrosis factor inhibitors, pulmonary fibrosis, toxicity, granuloma, sarcoidosis

Abbreviations: ADL, Adalimumab, BAL, Bronchoalveolar lavage, BSRBR, British Society of Rheumatology Biologics Registry, CD, Crohn's disease, COPD, Chronic obstructive pulmonary disease, DMARD, Disease-modifying anti-rheumatic drug, ECM, Extracellular matrix, ERATER, Early rheumatoid arthritis treatment evaluation registry, ET, Endothelin, ETN, Etanercept, IFN, Interferon, IFX, Infliximab, IL, Interleukin, ILD, Interstitial lung disease, LEF, Leflunomide, MMP, Matrix metalloprotease, MTX, Methotrexate, NICE, National Institute for Health and Clinical Excellence, PsA, Psoriatic arthritis, PDGF, Platelet-derived growth factor, RA, Rheumatoid arthritis, RCT, Randomized controlled trial, TACE, Tumor necrosis factor alpha converting enzyme, TGF, Transforming growth factor, TNF, Tumor necrosis factor, TNFi, Tumor necrosis factor inhibitors, TNFR, Tumor necrosis factor receptor