Leflunomide-induced interstitial lung disease: Prevalence and risk factors in Japanese patients with rheumatoid arthritis

Tetsuji Sawada, Shigeko Inokuma, Takeo Sato, Takeshi Otsuka, Yukihiko Saeki, Tsutomu Takeuchi, Takemasa Matsuda, Tamiko Takemura, Akira Sagawa

Research output: Contribution to journalArticlepeer-review

105 Citations (Scopus)


Objective: The possible link between LEF and interstitial lung disease (ILD) has evoked increasing concern. The aim of the present study was to elucidate the prevalence and risk factors for newly developed and/or exacerbated ILD, based on post-marketing surveillance data, in which all RA patients receiving LEF were pre-registered and monitored for 24 weeks in Japan. Methods: We analysed data from a cohort of 5054 RA patients who were prescribed LEF since its launch in September 2003 in Japan. Multivariable logistic analysis was performed to identify the risk factors for newly developed and/or exacerbation of ILD. Results: Sixty-one (1.2%) of 5054 RA patients who received LEF were reported to have development and/or exacerbation of ILD as an adverse drug reaction to LEF, judged by the attending physicians. Multivariable logistic regression analysis identified pre-existing ILD [odds ratio (OR) 8.17; 95% CI 4.63, 14.4], cigarette smoking (3.12; 95% CI 1.73, 5.60), a low body weight (<40 kg vs >50 kg) (2.91; 95% CI 1.15, 7.37) and the use of a loading dose (3.97; 95% CI 1.22, 12.9) as independent risk factors for LEF-induced ILD. Conclusions: Pre-existing ILD was the most important risk factor for LEF-induced ILD. We suggest that LEF should not be prescribed for RA patients complicated with ILD.

Original languageEnglish
Pages (from-to)1069-1072
Number of pages4
Issue number9
Publication statusPublished - 2009 Sept
Externally publishedYes


  • Adverse drug reaction
  • Interstitial lung disease
  • Leflunomide
  • Loading dose
  • Rheumatoid arthritis
  • Risk factor
  • Smoking

ASJC Scopus subject areas

  • Rheumatology
  • Pharmacology (medical)


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