RESEARCH - Arava-induced interstitial lung disease: prevalence and risk factors in Japanese patients with RA

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Rheumatology Advance Access published online on March 25, 2009

Rheumatology, doi:10.1093/rheumatology/kep052

Leflunomide-induced interstitial lung disease: prevalence and risk

factors in Japanese patients with rheumatoid arthritis

Tetsuji Sawada1, Shigeko Inokuma2, Takeo Sato2, Takeshi Otsuka3,

Yukihiko Saeki4, Tsutomu Takeuchi5, Takemasa Matsuda6, Tamiko

Takemura7, and Akira Sagawa8 on behalf of the Study Committee for

Leflunomide-induced Lung Injury, Japan College of Rheumatology

1Department of Rheumatology, Tokyo Medical University Hospital,

2Department of Allergy and Rheumatology, Japanese Red Cross Medical

Center, Tokyo, 3Munakata Medical Association Hospital, Fukuoka,

4Division of Allergy and Clinical Immunology, National Hospital

Organization, Osaka-Minami Medical Center, Osaka, 5Division of

Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama

Medical University, Saitama, 6Center for Rheumatic Diseases, Kagoshima

Red Cross Hospital, Kagoshima

7Department of Pathology, Japanese Red Cross Medical Center, Tokyo and

8Sagawa Akira Rheumatology Clinic, Sapporo, Japan.

Abstract

Objectives. 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.

http://rheumatology.oxfordjournals.org/cgi/content/abstract/kep052v1?papetoc

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