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Association between anti-TNF-? therapy and interstitial lung disease.

ABSTRACT: Anti-tumor necrosis factor-? (TNF-?) agents have been hypothesized to increase the risk of interstitial lung disease (ILD), including its most severe manifestation, pulmonary fibrosis.We conducted a cohort study among autoimmune disease patients who were members of Kaiser Permanente Northern California, 1998-2007. We obtained therapies from pharmacy data and diagnoses of ILD from review of X-ray and computed tomography reports. We compared new users of anti-TNF-? agents to new users of non-biologic therapies using Cox proportional hazards analysis to adjust for baseline propensity scores and time-varying use of glucocorticoids. We also made head-to-head comparisons between anti-TNF-? agents.Among the 8417 persons included in the analysis, 38 (0.4%) received a diagnostic code for ILD by the end of follow-up, including 23 of 4200 (0.5%) who used anti-TNF-? during study follow-up, and 15 of 5423 (0.3%) who used only non-biologic therapies. The age-standardized and gender-standardized incidence rate of ILD, per 100 person-years, was 0.21 [95% confidence interval (CI) 0-0.43] for rheumatoid arthritis and appreciably lower for other autoimmune diseases. Compared with the use of non-biologic therapies, use of anti-TNF-? therapy was not associated with a diagnosis of ILD among patients with rheumatoid arthritis (adjusted hazard ratio, 1.03; 95%CI 0.51-2.07), nor did head-to-head comparisons across anti-TNF-? agents suggest important differences in risk, although the number of cases available for analysis was limited.The study provides evidence that compared with non-biologic therapies, anti-TNF-? therapy does not increase the occurrence of ILD among patients with autoimmune diseases and informs research design of future safety studies of ILD.

SUBMITTER: Herrinton LJ

PROVIDER: S-EPMC3618622 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Association between anti-TNF-α therapy and interstitial lung disease.

Herrinton Lisa J LJ Harrold Leslie R LR Liu Liyan L Raebel Marsha A MA Taharka Ananse' A Winthrop Kevin L KL Solomon Daniel H DH Curtis Jeffrey R JR Lewis James D JD Saag Kenneth G KG

Pharmacoepidemiology and drug safety 20130129 4

<h4>Background</h4>Anti-tumor necrosis factor-α (TNF-α) agents have been hypothesized to increase the risk of interstitial lung disease (ILD), including its most severe manifestation, pulmonary fibrosis.<h4>Methods</h4>We conducted a cohort study among autoimmune disease patients who were members of Kaiser Permanente Northern California, 1998-2007. We obtained therapies from pharmacy data and diagnoses of ILD from review of X-ray and computed tomography reports. We compared new users of anti-TNF ...[more]

PMID: 23359391

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Project description:Interstitial lung abnormalities have been associated with lower 6-minute walk distance, diffusion capacity for carbon monoxide, and total lung capacity. However, to our knowledge, an association with mortality has not been previously investigated.To investigate whether interstitial lung abnormalities are associated with increased mortality.Prospective cohort studies of 2633 participants from the FHS (Framingham Heart Study; computed tomographic [CT] scans obtained September 2008-March 2011), 5320 from the AGES-Reykjavik Study (Age Gene/Environment Susceptibility; recruited January 2002-February 2006), 2068 from the COPDGene Study (Chronic Obstructive Pulmonary Disease; recruited November 2007-April 2010), and 1670 from ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints; between December 2005-December 2006).Interstitial lung abnormality status as determined by chest CT evaluation.All-cause mortality over an approximate 3- to 9-year median follow-up time. Cause-of-death information was also examined in the AGES-Reykjavik cohort.Interstitial lung abnormalities were present in 177 (7%) of the 2633 participants from FHS, 378 (7%) of 5320 from AGES-Reykjavik, 156 (8%) of 2068 from COPDGene, and in 157 (9%) of 1670 from ECLIPSE. Over median follow-up times of approximately 3 to 9 years, there were more deaths (and a greater absolute rate of mortality) among participants with interstitial lung abnormalities when compared with those who did not have interstitial lung abnormalities in the following cohorts: 7% vs 1% in FHS (6% difference [95% CI, 2% to 10%]), 56% vs 33% in AGES-Reykjavik (23% difference [95% CI, 18% to 28%]), and 11% vs 5% in ECLIPSE (6% difference [95% CI, 1% to 11%]). After adjustment for covariates, interstitial lung abnormalities were associated with a higher risk of death in the FHS (hazard ratio [HR], 2.7 [95% CI, 1.1 to 6.5]; P?=?.03), AGES-Reykjavik (HR, 1.3 [95% CI, 1.2 to 1.4]; P?<?.001), COPDGene (HR, 1.8 [95% CI, 1.1 to 2.8]; P?=?.01), and ECLIPSE (HR, 1.4 [95% CI, 1.1 to 2.0]; P?=?.02) cohorts. In the AGES-Reykjavik cohort, the higher rate of mortality could be explained by a higher rate of death due to respiratory disease, specifically pulmonary fibrosis.In 4 separate research cohorts, interstitial lung abnormalities were associated with a greater risk of all-cause mortality. The clinical implications of this association require further investigation.

Dataset Information

Association between anti-TNF-? therapy and interstitial lung disease.

Publications

Association between anti-TNF-α therapy and interstitial lung disease.

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