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

Lisa J. Herrinton, Leslie R. Harrold, Liyan Liu, Marsha A. Raebel, Ananse' Taharka, Kevin L. Winthrop, Daniel H. Solomon, Jeffrey R. Curtis, James D. Lewis, Kenneth G. Saag

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


Background: 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. 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-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. 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-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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)394-402
Number of pages9
JournalPharmacoepidemiology and Drug Safety
Issue number4
StatePublished - Apr 2013


  • Adverse events
  • Automated healthcare data
  • Cohort studies
  • Crohn's disease
  • Drug safety
  • Drug toxicity
  • Inflammatory bowel disease
  • Interstitial lung disease
  • Pharmacoepidemiology
  • Propensity scores
  • Psoriasis
  • Psoriatic arthritis
  • Pulmonary fibrosis
  • Rheumatoid arthritis
  • Ulcerative colitis

ASJC Scopus subject areas

  • Epidemiology
  • Pharmacology (medical)


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