Proposals for leflunomide use to avoid lung injury in patients with rheumatoid arthritis.
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.
Study Committee for Leflunomide-Induced Lung Injury, Japan College of Rheumatology, 1-1-24 Toranomon, Minato-ku, and Department of Allergy and Immunological Diseases, Tokyo Metropolitan Komagome Hospital, Tokyo, 105-0011, Japan.
Shigeko
S
Inokuma
Takeo
T
Sato
Akira
A
Sagawa
Takemasa
T
Matsuda
Tamiko
T
Takemura
Takeshi
T
Ohtsuka
Yukihiko
Y
Saeki
Tsutomu
T
Takeuchi
Tetsuji
T
Sawada
D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000009:adverse effects*; D007564:Japan; D000077339:Leflunomide; D055370:Lung Injury / Q000139:chemically induced* / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D017410:Practice Guidelines as Topic; D012189:Retrospective Studies
D018501:Antirheumatic Agents; D007555:Isoxazoles; D000077339:Leflunomide