THU0180 RISK MODIFICATION OF TUBERCULOSIS INFECTION BY CHEMOPROPHYLAXIS AMONG PATIENTS WITH RHEUMATOID ARTHRITIS RECEIVING TNF INHIBITORS: A NATION-WIDE COHORT STUDY
Authors: A. Shin, E. H. Park, Y. J. Ha, Y. J. Lee, Y. W. Song, E. H. Kang
Journal: Annals of the Rheumatic Diseases (2020)

Background: Based on the benefit of chemoprophylaxis among patients receiving biologics [1], Health Insurance Review and Assessment (HIRA) service of Korea requires patients to undergo latent tuberculosis (LT) screening before initiation of any biologics and to receive chemoprophylaxis for positive LT. Objectives: To assess the effect of chemoprophylaxis on tuberculosis infection (TI) risk among patients with rheumatoid arthritis (RA) receiving biologics in Korea Methods: Using 2002-2016 Korea National Health Insurance database, we conducted a cohort study on RA patients initiating biologic drugs (TNF inhibitors, abatacept, tocilizumab) to compare TI risk between those who started isoniazid and/or rifampin within 1 year before biologics initiation (prophylaxis group) versus those who did not (non-prophylaxis group). TI was defined by ICD10 codes plus anti-tuberculosis medications as previously described [2]. Patients were followed-up from biologics initiation to censoring events (TI occurrence, death, biologics discontinuation, initiation of anti-tuberculosis drug due to non-TI cause, and end of database). To control &gt;50 baseline confounders, we used propensity score (PS)-based fine stratification and weighting. A weighted Cox proportional hazards model estimated hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Before PS stratification (PSS) and weighting, we identified 2,250 and 7,259 RA patients for prophylaxis and non-prophylaxis group, respectively. Mean age was 57.6 years and 81.3% female. Three-fourths of patients in the prophylaxis group completed &gt;70% of recommended treatment periods [3]. The incidence rate of TI per 100 person-years was 0.33 for prophylaxis group versus 0.57 for non-prophylaxis group. 28% of all TI cases (n=34) were extra-pulmonary with gastrointestinal (n=11) and miliary TI (n=9) being most common. The PSS-weighted HR (95% CI) of TI comparing prophylaxis versus non-prophylaxis group was 0.52 (0.32-0.86) (Table 1, Figure 1). Sensitivity analyses showed that the chemoprophylaxis was particularly effective for those with younger age (&lt;65 years), male gender, or high comorbidity (≥ median value) (Table 1). Table 1. Comparative risk of tuberculosis infection between prophylaxis versus non-prophylaxis group Crude PSS-weighted N Events PY IR per 100 person-years HR (95% CI ) Primary as-treated analysis 1 Total P 2,250 18 5,532 0.33 0.52 (0.32-0.86) NP 7,259 100 17,503 0.64 ITT analyses 1 1 year ITT P 2,250 10 2,115 0.47 0.33 (0.17-0.64) NP 7,259 97 6,833 1.42 2 year ITT P 2,250 21 3,907 0.54 0.49 (0.31-0.78) NP 7,259 140 12,698 1.10 4 year ITT P 2,250 31 6,305 0.49 0.56 (0.38-0.82) NP 7,259 181 21,278 0.88 Sensitivity Analyses Age &lt;65 years P 1,751 9 4,588 0.20 0.39 (0.19-0.78) NP 5,345 72 13,634 0.52 Male P 546 2 1,319 0.15 0.12 (0.03-0.50) NP 1,235 28 2,624 1.33 Comorbidity score ≥3 P 824 6 1,908 0.31 0.34 (0.15-0.79) NP 2,668 52 6,129 0.94 1 As-treated analysis censored patients when they discontinued biologics use, while ITT analysis did not. IR=incidence rate; ITT=intention-to-treat; HR=hazard ratio; PSS=propensity-score stratification; CI=confidence interval; PY=person-years; P=prophylaxis group; NP=non-prophylaxis group Conclusion: We found 48% risk reduction of TI by chemo-prophylaxis among RA patients receiving biologics. Due to HIRA requirements, a majority of non-prophylaxis group were considered negative for LT by screening at biologics initiation [4]. These findings indicate that the risk of TI during bDMARD treatment is still high among RA patients who were negative for LT at baseline but did not undergo chemoprophylaxis, which is double the risk among RA patients who had LT and underwent chemoprophylaxis. References: [1]Carmona L et al. Arthritis Rheum. 2005;52:1766-72. [2]Lee J et al. Ann Am Thorac Soc. 2017;14:690-697. [3]https://www.cdc.gov/tb/topic/treatment/ltbi.htm [4]Kim ES et al. World J Gastroenterol. 2015;21:3308-16. Disclosure of Interests: None declared