Association between anti-TNF-α therapy and interstitial lung disease
Article first published online: 29 JAN 2013
Copyright © 2013 John Wiley & Sons, Ltd.
Pharmacoepidemiology and Drug Safety
Volume 22, Issue 4, pages 394–402, April 2013
How to Cite
Herrinton, L. J., Harrold, L. R., Liu, L., Raebel, M. A., Taharka, A., Winthrop, K. L., Solomon, D. H., Curtis, J. R., Lewis, J. D. and Saag, K. G. (2013), Association between anti-TNF-α therapy and interstitial lung disease. Pharmacoepidem. Drug Safe., 22: 394–402. doi: 10.1002/pds.3409
- Issue published online: 1 APR 2013
- Article first published online: 29 JAN 2013
- Manuscript Accepted: 25 DEC 2012
- Manuscript Revised: 14 DEC 2012
- Manuscript Received: 17 AUG 2012
- Rheumatoid arthritis;
- psoriatic arthritis;
- Crohn's disease;
- ulcerative colitis;
- inflammatory bowel disease;
- drug safety;
- drug toxicity;
- adverse events;
- cohort studies;
- propensity scores;
- automated healthcare data;
- interstitial lung disease;
- pulmonary fibrosis
Anti-tumor necrosis factor-α (TNF-α) agents have been hypothesized to increase the risk of interstitial lung disease (ILD), including its most severe manifestation, pulmonary fibrosis.
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-α 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-α agents.
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-α 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-α 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-α agents suggest important differences in risk, although the number of cases available for analysis was limited.
The study provides evidence that compared with non-biologic therapies, anti-TNF-α therapy does not increase the occurrence of ILD among patients with autoimmune diseases and informs research design of future safety studies of ILD. Copyright © 2013 John Wiley & Sons, Ltd.