Association between anti-TNF-alpha therapy and interstitial lung disease

UMMS Affiliation

Meyers Primary Care Institute; Department of Medicine, Division of Rheumatology; Department of Orthopedics and Physical Rehabilitation

Publication Date


Document Type



Tumor Necrosis Factor-alpha; Lung Diseases, Interstitial


Clinical Epidemiology | Health Services Research | Pharmacy and Pharmaceutical Sciences | Respiratory Tract Diseases


BACKGROUND: Anti-tumor necrosis factor-alpha (TNF-alpha) agents have been hypothesized to increase the risk of interstitial lung disease (ILD), including its most severe manifestation, pulmonary fibrosis.

METHODS: We conducted a cohort study among autoimmune disease patients who were members of Kaiser Permanente Northern California, 1998-2007. We obtained therapies from pharmacy data and diagnoses of ILD from review of X-ray and computed tomography reports. We compared new users of anti-TNF-alpha agents to new users of non-biologic therapies using Cox proportional hazards analysis to adjust for baseline propensity scores and time-varying use of glucocorticoids. We also made head-to-head comparisons between anti-TNF-alpha agents.

RESULTS: Among the 8417 persons included in the analysis, 38 (0.4%) received a diagnostic code for ILD by the end of follow-up, including 23 of 4200 (0.5%) who used anti-TNF-alpha during study follow-up, and 15 of 5423 (0.3%) who used only non-biologic therapies. The age-standardized and gender-standardized incidence rate of ILD, per 100 person-years, was 0.21 [95% confidence interval (CI) 0-0.43] for rheumatoid arthritis and appreciably lower for other autoimmune diseases. Compared with the use of non-biologic therapies, use of anti-TNF-alpha therapy was not associated with a diagnosis of ILD among patients with rheumatoid arthritis (adjusted hazard ratio, 1.03; 95%CI 0.51-2.07), nor did head-to-head comparisons across anti-TNF-alpha agents suggest important differences in risk, although the number of cases available for analysis was limited.

CONCLUSION: The study provides evidence that compared with non-biologic therapies, anti-TNF-alpha therapy does not increase the occurrence of ILD among patients with autoimmune diseases and informs research design of future safety studies of ILD. Copyright (c) 2013 John Wiley and Sons, Ltd.

DOI of Published Version



Pharmacoepidemiol Drug Saf. 2013 Apr;22(4):394-402. doi: 10.1002/pds.3409. Link to article on publisher's site

Journal/Book/Conference Title

Pharmacoepidemiology and drug safety

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Link to Article in PubMed

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