Rheumatoid Arthritis Treatment and the Risk of Severe Interstitial Lung Disease

Interstitial lung disease (ILD) is an important complication of rheumatoid arthritis (RA) or its treatment, and is associated with substantially increased mortality. Reports have suggested that infliximab with or without azathioprine might lead to rapidly progressive or fatal ILD. Researchers at the Arthritis Research Center Foundation, Wichita, used an RA data bank to assess the associations of treatments for RA and severe ILD.

The researchers identified ILD in hospitalisations and death records in 100 of 17,598 RA patients and studied it in relation to RA therapy with Cox regression analyses. The incidence of hospitalisation for ILD (HILD) was 260 per 100,000 patient years. Among those hospitalised for ILD, 27.0% died. In multivariable models of current and past RA treatment, the only current treatment associated with HILD was prednisone: hazard ratio (HR) 2.5 [95% confidence interval (CI) 1.5-4.1]. Among past therapies, prednisone (HR 3.0, 95% CI 1.0-8.9), infliximab (HR 2.1, 95% CI 1.1-3.8), etanercept (HR 1.7, 95% CI 1.0-3.0), and cyclophosphamide (HR 3.7, 95% CI 0.9-15.5) were associated with HILD. Pre-existing lung problems were identified in 67% of HILD. Only one case of HILD in the 100 hospitalisations suggested a possible temporal relationship between infliximab and HILD. Associations between RA treatment and HILD are confounded by the prescription of treatments for ILD such as prednisone, infliximab, etanercept, and cyclophosphamide. The researchers found no clear pattern of causal association of treatment and ILD, and no clear evidence to support a causal relationship between infliximab, azathioprine, and HILD.(Source: Wolfe F, Caplan L, Michaud K. Rheumatoid arthritis treatment and the risk of severe interstitial lung disease. Scand J Rheumatol. 2007 May-Jun;36(3):172-8. : August 2007)