Interstitial lung disease induced or exacerbated by TNF-targeted therapies: Analysis of 122 cases

Seminars in Arthritis and Rheumatism, 02/17/2011

Perez-Alvarez R et al. – The authors found that 97% of cases of ILD associated with biologic agents were associated with agents blocking tumor necrosis factor-α, a cytokine that has been implicated in the pathophysiology of pulmonary fibrosis. Drug-induced ILD had a poor prognosis, with an overall mortality rate of around one third, rising to two thirds in patients with preexisting ILD


  • In 2006, Study Group on Autoimmune Diseases of Spanish Society of Internal Medicine created BIOGEAS project
  • One objective was to collect data on autoimmune diseases secondary to use of biologic agents by quarterly Medline search surveillance of reported cases
  • Baseline included articles published between January 1990 and March 2010, including MeSH term “lung diseases, interstitial” as key research term
  • Report an unpublished case of ILD secondary to biologic therapy


  • 122 reported cases of new-onset or exacerbation of ILD secondary to administration of biologic therapies
  • Biologic agents associated with ILD overwhelmingly anti-tumor necrosis factor agents (etanercept in 58 cases and infliximab in 56) and administered for RA in 108 (89%) patients
  • ILD appeared mean of 26 weeks after initiation of biologic agents
  • ILD confirmed by pulmonary biopsy in 26 cases, although specific histopathologic description detailed in only 20: 7 patients classified as usual interstitial pneumonia, 6 as nonspecific interstitial pneumonia, 5 as organizing pneumonia, 1 as diffuse alveolar damage, and 1 as lymphoid interstitial pneumonia
  • Treatment of ILD included withdrawal of biologic agents in all cases but 1
  • The outcome of ILD was detailed in 52 cases
  • Complete resolution reported in 21 (40%) cases, improvement or partial resolution in 13 (25%), and no resolution in 18 (35%)
  • 15 (29%) patients died during follow-up, majority (70%) during first 5 weeks after initiating biologic therapy
  • In comparison with survivors, patients who died were aged >65 years (67% vs 33%, P = 0.036), with later onset of ILD (46 weeks vs 15 weeks, P = 0.006)
  • Received immunosuppressive drugs more frequently (33% vs 8%, P = 0.036), and more often had a previous diagnosis of ILD (67% vs 29%, P = 0.025)

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