Association between anti-TNF-alpha therapy and interstitial lung disease

作者：Herrinton Lisa J^*; Harrold Leslie R; Liu Liyan; Raebel Marsha A; Taharka Ananse' Winthrop Kevin L; Solomon Daniel H; Curtis Jeffrey R; Lewis James D; Saag Kenneth G

来源：Pharmacoepidemiology and Drug Safety, 2013, 22(4): 394-402.

DOI：10.1002/pds.3409

• Rheumatoid arthritis
• psoriatic arthritis
• psoriasis
• Crohn%26apos
• s disease
• ulcerative colitis
• inflammatory bowel disease
• pharmacoepidemiology
• drug safety
• drug toxicity
• adverse events
• cohort studies
• propensity scores
• automated healthcare data
• interstitial lung disease
• pulmonary fibrosis

Background 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. Methods We conducted a cohort study among autoimmune disease patients who were members of Kaiser Permanente Northern California, 19982007. 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. Results 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) 00.43] 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 0.512.07), 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. Conclusion 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.

• 出版日期2013-4