Rheumatoid arthritis treatment and the risk of severe interstitial lung disease

F. Wolfe, L. Caplan, K. Michaud

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Objectives: 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. We used an RA data bank to assess the associations of treatments for RA and severe ILD. Methods: ILD was identified in hospitalisations and death records in 100 of 17 598 RA patients and studied in relation to RA therapy with Cox regression analyses. Results: 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. Conclusions: Associations between RA treatment and HILD are confounded by the prescription of treatments for ILD such as prednisone, infliximab, etanercept, and cyclophosphamide. There is no clear pattern of causal association of treatment and ILD, and there is no clear evidence to support a causal relationship between infliximab, azathioprine, and HILD.

Original languageEnglish (US)
Pages (from-to)172-178
Number of pages7
JournalScandinavian Journal of Rheumatology
Volume36
Issue number3
DOIs
StatePublished - Aug 3 2007

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Interstitial Lung Diseases
Rheumatoid Arthritis
Hospitalization
Confidence Intervals
Prednisone
Therapeutics
Azathioprine
Cyclophosphamide
Death Certificates
Prescriptions
Regression Analysis
Infliximab
Databases
Lung
Mortality
Incidence

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

Rheumatoid arthritis treatment and the risk of severe interstitial lung disease. / Wolfe, F.; Caplan, L.; Michaud, K.

In: Scandinavian Journal of Rheumatology, Vol. 36, No. 3, 03.08.2007, p. 172-178.

Research output: Contribution to journalArticle

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abstract = "Objectives: 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. We used an RA data bank to assess the associations of treatments for RA and severe ILD. Methods: ILD was identified in hospitalisations and death records in 100 of 17 598 RA patients and studied in relation to RA therapy with Cox regression analyses. Results: 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. Conclusions: Associations between RA treatment and HILD are confounded by the prescription of treatments for ILD such as prednisone, infliximab, etanercept, and cyclophosphamide. There is no clear pattern of causal association of treatment and ILD, and there is no clear evidence to support a causal relationship between infliximab, azathioprine, and HILD.",
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