Neue Studien

Leflunomide-induced interstitial lung disease

Japanes’ experience:
Leflunomide-induced interstitial lung disease: prevalence and risk factors in Japanes patients with rheumatoid arthritis
Sawada T, Inokuma S et al.; Rheumatol 2009; doi: 10.1093/rheuamtology/kep052

Objective: Evaluation of the prevalence and risk factors for newly developed or exacerbated interstitial lung disease based on post-marketing surveillance data.

Methods: Analysed were data from a cohort of 5054 RA-patients who received Leflunomide.

Results: 61 (1.2%) of 5054 RA-patients who received Leflunomide were reported to have development and/or exacerbation of interstitial lung disease as an adverse drug reaction to Leflunomide as judged by the attending physician. Independent risk factors for Leflunomide-induced lung disease were identified as pre-existing lung disease, smoking, low body weight and the use of a loading dose of Leflunomide.

Conclusions: Pre-existing interstitial lung disease was the most important risk factor for Leflunomide induced interstitial lung disease. It is suggested that Leflunomide should not be prescribed for RA-patients with interstitial lung disease.


Literature review:
Clinical expression of Leflunomide-induced pneumonitis
Chikura B, Lane S, Dawson JK. Rheumatol 2009 doi: 10.1093/rheumatology/kep050

Objective: Review of current evidence of Leflunomide-induced pneumonitis.

Methods: 32 reported cases of Leflunomide-induced pneumonitis (13 males and 19 females) were identified from literature research.

Results: All patients had a history of either exposure to MTX or interstitial lung disease or both, all patients had RA. 82% of the patients developed pneumonitis within the first 20 weeks of exposure to Leflunomide. All patients had a loading dose. Mortality was 19%. 2 patients had previous MTX-induced pneumonitis prior to the initiation of Leflunomide (both died from pneumonitis under Leflunomide). Treatment with Cholastyramine did not appear to alter clinical outcome.

Conclusions: Leflunomide-induced pneumonitis usually occurs within the first 20 weeks of treatment. Pre-existing pneumopathy is a pour prognostic indicator. Leflunomide should not be used in patients with previous MTX pneumonitis and should be used with caution in patients with interstitial lung disease.

Comment: Similar to MTX Leflunomide may induce pneumonitis (interstitial lung disease). The two studies show, that the prevalence of pneumonitis is rare, however, it may be associated with a high mortality. For rheumatologists it is important to know that this complication may occur under Leflunomide. In my view Leflunomide should not be given to any patient with previous pneumonitis (under MTX or not) and with interstitial lung disease.

Beat A. Michel

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