Vol.18 No.5

Review Article

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

Authors

Shigeko Inokuma1,2 , Takeo Sato1,3 , Akira Sagawa1,4 , Takemasa Matsuda1,5 , Tamiko Takemura1,6 , Takeshi Ohtsuka1,7 , Yukihiko Saeki1,8 , Tsutomu Takeuchi1,9 , Tetsuji Sawada1,10

  • Study Committee for Leflunomide-Induced Lung Injury, Japan College of Rheumatology, 1-1-24 Toranomon, Minato-ku, Tokyo, 105-0011, Japan
  • Department of Allergy and Immunological Diseases, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
  • Department of Allergy and Rheumatology, Japanese Red Cross Medical Center, 4-1-22 Hiroo, Shibuya-ku, Tokyo, 150-8935, Japan
  • Sagawa Akira Rheumatology Clinic, Sapporo, Japan
  • The Center for Rheumatic Diseases, Kagoshima Red Cross Hospital, Kagoshima, Japan
  • Department of Pathology, Japanese Red Cross Medical Center, Tokyo, Japan
  • Department of Internal Medicine, Munakata Medical Association Hospital, Fukuoka, Japan
  • Division of Allergy and Clinical Immunology, National Hospital Organization, Osaka-Minami Medical Center, Osaka, Japan
  • Division of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, Saitama, Japan
  • 10. Department of Allergy and Rheumatology, University of Tokyo School of Medicine, Tokyo, Japan
Received:

7 December 2007

Accepted:

11 March 2008

Published online:

13 June 2008

Full Text

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Abstract

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.

Key words

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