Proposals for leflunomide use to avoid lung injury in patients with rheumatoid arthritis

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

Research output: Contribution to journalReview articlepeer-review

14 Citations (Scopus)


Among the 5,043 consecutive patients registered in the postmarketing surveillance for leflunomide, 61 were reported to have lung injury and 24 died from it. The adjusted multivariate logistic regression analysis of the risk factors showed that preexisting interstitial lung disease posed the greatest risk, as well as loading dose, smoking history, and low body weight of 40 kg or less with odds ratios of 8.17, 3.97, 3.12, and 2.91, respectively. In 12 patients, lung injury developed even 2 months after leflunomide withdrawal. When patients with (n = 9) and without (n = 13) fatal outcome were compared, eight out of the former, and six out of the latter had preexisting interstitial lung disease; the former showed severe hypoxemia, high serum C-reactive protein level, hypoalbuminemia, and continuous lymphocytopenia, and required mechanical ventilation. On the basis of these results and literature review, the committee proposes that leflunomide should only be recommended as a second-line drug, should not be administered to patients with preexisting interstitial lung disease, should also not be administered to patients with smoking history or those with low body weight, and should be administered without loading dose. Careful monitoring is necessary, and when lung injury develops, leflunomide elimination using colestyramine is mandatory.

Original languageEnglish
Pages (from-to)442-446
Number of pages5
JournalModern rheumatology
Issue number5
Publication statusPublished - 2008
Externally publishedYes


  • Leflunomide
  • Lung injury
  • Proposals for leflunomide use
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Medicine(all)


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