FACTORS ASSOCIATED WITH THE RISK OF SEPSIS IN PATIENTS WITH IMMUNE-MEDIATED INFLAMMATORY DISEASES TREATED WITH ANTI-TUMOR NECROSIS FACTOR-ALPHA: A NATIONWIDE, POPULATIONBASED COHORT STUDY

Background: Anti-TNF-α agents have been proven to be effective for patients with immune-medicated inflammatory diseases (IMIDs) including rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriasis (PsO), psoriatic arthritis (PsA), Crohn’s disease (CD) and ulcerative colitis (UC). Prior studies have shown an increased risk of infection in IMID patients treated with anti-TNF-α but limited studies investigated factors associated with the development of sepsis in patients with IMIDs. Objectives: To investigate factors associated with the development of sepsis in patients with IMIDs using the Taiwanese National Health Insurance Research Database (NHIRD). Methods: We identified all biologic-naive patients with RA, AS, PsO, PsA, or CD/UC from the claim data via the NHIRD who started their first anti-TNF-α agent (etanercept (ETN), adalimumab (ADA) or golimumab (GOL)) between 2003 and 2017 as study subjects. The index date was the first date of anti-TNF-α prescription. Sepsis was defined based on the sepsis-3 definition. We identified sepsis patients using a validated ICD-9-CM coding system proposed by Angus et al, in which a diagnosis of bacterial/fungal infection with one or more acute organ dysfunction is required to define an episode of sepsis. All study subjects were followed up till the date of first hospitalization due to sepsis, 90 days after the last date of anti-TNF-α prescription, withdrawal from NHIRD or death, whichever came first. We used a Cox regression analysis to assess the associations of covariates with the risk of sepsis shown as hazard ratios (HRs) with 95% confidence interval (CIs). Covariates included anti-TNF-α agent, IMID, age, sex, insured amount, level of urbanization, disease duration, Charlson comorbidity index (CCI), a history of prior hospitalization due to sepsis within 3 months before the index date and medication use within 12 months before the index date and during the follow-up period. Results: We identified 18105 biologic-naive patients with IMIDs, including 8123 ETN users, 7623 ADA users and 2359 GOL users. The incidence rates (IRs) of sepsis in patients treated with ETN, ADA and GOL were 1080, 1181, and 617 per 105 years respectively. Multivariable regression analyses showed that factors associated with an increased risk of sepsis were use of ADA (ETN as reference: HR, 1.21; 95% CI, 1.02–1.42), male (HR, 1.24; 95% CI, 1.04–1.48), age (HR, 1.06; 95% CI, 1.05–1.07), CD/UC (HR, 2.35; 95% CI, 1.57–3.53), CCI (HR, 1.30; 95% CI, 1.23–1.38), prior sepsis (HR, 2.42; 95% CI, 1.78–3.29), prior use of sulfasalazine (HR, 1.25, 95% CI, 1.00-1.55), lower levels of urbanization (level III: HR, 1.37; 95% CI, 1.06–1.77; level IV: HR, 1.68, 95% CI, 1.35–2.10). Factors associated with a decreased risk of sepsis were use of GOL (ETN as reference: HR, 0.59; 95% CI, 0.39–0.84), use of methotrexate (HR, 0.78; 95% CI, 0.65–1.00), and higher insured amount (reference: ≤ 15480 NTD; 15480–28800 NTD: HR, 0.83; 95% CI, 0.68–0.99; 28800–45800 NTD: HR, 0.58; 95% CI, 0.45–0.74; \u003e45800 NTD: HR, 0.33; 95% CI, 0.21–0.54). Conclusion: Our study revealed that among biologic-naive IMID patients initiating anti-TNF-α treatment, use of ADA, age, sex, CD/UC, CCI, prior sepsis, prior use of sulfasalazine and lower levels of urbanization were associated with an increased risk of sepsis, while use of GOL, use of methotrexate, and higher insured amount were associated with a decreased risk of sepsis. Disclosure of Interests: BO-CHUEN HSU: None declared, Hsin-Hua Chen: None declared, Ching-Heng Lin: None declared, Yi-Ming Chen: None declared, Kuo-Lung Lai: None declared, Der-Yuan Chen: None declared, Wen-Nan Huang: None declared, Yi-Hsing Chen Grant/research support from: Taiwan Ministry of Science and Technology, Taiwan Department of Health, Taichung Veterans General Hospital, National Yang-Ming University, GSK, Pfizer, BMS., Consultant of: Pfizer, Novartis, Abbvie, Johnson \u0026 Johnson, BMS, Roche, Lilly, GSK, Astra\u0026 Zeneca, Sanofi, MSD, Guigai, Astellas, Inova Diagnostics, UCB, Agnitio Science Technology, United Biopharma, Thermo Fisher, Gilead., Paid instructor for: Pfizer, Novartis, Johnson \u0026 Johnson, Roche, Lilly, Astra\u0026 Zeneca, Sanofi, Astellas, Agnitio Science Technology, United Biopharma., Speakers bureau: Pfizer, Novartis, Abbvie, Johnson \u0026 Johnson, BMS, Roche, Lilly, GSK, Astra\u0026 Zeneca, Sanofi, MSD, Guigai, Astellas, Inova Diagnostics, UCB, Agnitio Science Technology, United Biopharma, Thermo Fisher, Gilead.