Risk of Infection in Tumor Necrosis Factor-α Users in Korea Population : 종양괴사인자-알파 길항제 치료를 받고 있는 한국 환자에게서 감염 위험도 조사

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보건대학원 보건학과(보건학전공)
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서울대학교 대학원
학위논문 (석사)-- 서울대학교 대학원 : 보건대학원 보건학과(보건학전공), 2018. 8. 원성호.
Background/Objectives: Tumor necrosis factor-α (TNF-α) inhibitors are treatment choices for autoimmune and inflammatory diseases. Because of their wide range of biological effects in host defense, one of safety concerns using TNF-α inhibitors is risk of infection. The study was to evaluate whether the risk of overall and serious infections increase in patients treated with TNF-α inhibitors for rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, Crohns disease or ulcerative colitis (TNF-α inhibitor cohort) compared to non-TNF-α inhibitors patients with those diseases (comparison cohort), and to identify risk factors of developing infections in TNF-α inhibitor users.

Method: The national standard cohort 2.0 database (NHIS-NSC2) was used which contains health data of approximately one million of Koreans from the year of 2002 to 2015. Because of imbalances in numbers of patients in each cohort and differences in baseline characteristics, propensity score matching using greedy nearest neighbor matching method was performed. Overall infections and serious infections of patients in the TNF-α inhibitors and comparison cohorts during follow-up period including 90 days of lag period were counted and analyzed. For comparison, incidence rate ratio were calculated using Poisson regression, and cox regression was used for hazard ratio for time-to-first infection occurrence.

Results: Total 548 patients in the TNF-α inhibitor cohort and 4,019 patients in the comparison cohort were identified as meeting all inclusion and exclusion criteria of the study. After 1:1 matching based on propensity score, 539 patients were included in each cohorts. There were no statistically significance in baseline characteristics between two cohorts. Total 1743.7210 person-years was observed in patients of the TNF-α inhibitor cohort with median follow-up of 3.2351 person-years. For the comparison cohort, total 1589.5340 person years with median 2.9490 person-years per person were observed. Crude incidence rate of infection was 8.5593 (95% CI 8.4231 – 8.6977) for the TNF-α inhibitor cohort and 7.8501 (95% CI 7.7136 – 7.9891) for the comparison cohort. IRR of infection was significantly higher in the TNF-α inhibitor cohort 1.0903 (95% CI 1.0647 – 1.1166), and same findings were observed in adjusted IRR. However, opposite pattern was shown in incidence rate and IRR of serious infection. In the TNF-α inhibitor cohort, crude incidence rate in 90-day risk period was higher in the rate in 365-day risk period - 8.2785 (95% CI 7.7885 – 8.7993) and 7.8879 (95% CI 7.6322 – 8.1522) respectively. Among patients in the TNF-α inhibitor cohort, one-time users had the highest incidence rate of infection (26.1793) and patients with less than 6-month uses had the highest incidence rate of serious infection (1.2516). Total 14,925 infections in 476(88.3%) patients and 764 serious infections in 209 patients (38.8%) were observed in the TNF-α inhibitor cohort. In the comparison cohort, 12,478 infections in 468 patients (86.8%) and 983 serious infections in 226 (41.9%) were observed. In both cohorts, acute bronchitis was the most frequently observed infection and serious infection, and respiratory infection was the most frequently observed type of diseases. More patients in the TNF-α inhibitor cohort had infections under national surveillance, however, this pattern was not found in serious infection. There was no difference in frequency and number of patients in skin related infections. Hazard ratio considering first infection was calculated, and there was no statistical significance.

Conclusion: In this study, increased IRR of infection in the TNF-α inhibitor cohort were found compared to the comparison cohort. 88.3% patients in the TNF-α inhibitors cohort experienced infection, and 38.8% patients had serious infection. Though some findings were not prone to support increased risk of infection associated with TNF-α inhibitor uses, potential increased risk of infection cannot be overlooked. In addition, glucocorticoid use is an independent risk factor of infection, and this medication is commonly used among patients with inflammatory or autoimmune diseases. Therefore, attention to occurrence of infection is required to patients with inflammatory or autoimmune disease who are on immunosuppressant medications since occurrence of infection gives extra burdens to patients in terms of physical stress and can lead to treatment discontinuation.
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Graduate School of Public Health (보건대학원)Dept. of Public Health (보건학과)Theses (Master's Degree_보건학과)
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