한국인 류마티스 질환 환자에서의 잠복결핵과 B형 간염

Abstract

Objectives The purpose of this study is to estimate the positivity and agreement between QuantiFERON-TB Gold in tube Test (QFT-GIT) and Tuberculin Skin Test (TST) according to underlying rheumatic diseases and to identify the influencing factors on discrepancies between two tests and also to evaluate the difference in the occurrence of active TB in patients who are candidates of biologic agents who receive both QFT-GIT and TST compared with those who receive only TST or only QFT-GIT for detection of latent mycobacterium tuberculosis infection (LTBI). And finally, we investigated the impact of treatment for rheumatoid arthritis (RA) in patients with hepatitis B.

Materials and Methods 1. Latent Mycobacterium Tuberculosis in Korean Patients with Rheumatic Disease 1) Factors Influencing Discrepancies Between QFT-GIT and TST Among the 757 patients who underwent both QFT-GIT and TST simultaneously from Sept. 2008 to Nov. 2010, patients with indeterminate QFT-GIT result (N=21), with active (N=11) or suspicious (N=1) for tuberculosis on a chest radiograph were excluded. Finally, 724 patients were recruited for this study; 497 patients with RA, 198 with AS, and 29 with JRA. The agreement between two tests was estimated by Cohen’s kappa (κ) and factors influencing discrepancies were identified using multivariate analysis.

2) Evaluation of the Usefulness of QFT-GIT and TST for Detection of LTBI The 1919 patients who underwent QFT-GIT or TST from Jan. 2007 to Dec. 2012 were recruited for this study. The screening test of LTBI, TB prophylaxis, TB occurrence, and clinical characteristics were examined about 842 patients who received QFT-GIT or TST and used biologics. Among 842 patients, 260 patients received only TST, 149 patients received only QFT-GIT, and 436 patients received both QFT-GIT and TST. The occurrence of TB according to the screening method of LTBI was identified. The incidence rates of active TB were calculated as number of events per 100,000 person-years exposure.

2. Hepatitis B in Korean Patients with Rheumatic Disease 1) Treatment and Outcomes of Rheumatoid Arthritis Patients with Hepatitis B Patients enrolled in KORONA (Korean Observational Study Network for Arthritis) with 1-year follow up assessment with data on hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) status were included in the analysis. Patient characteristics (age, sex, disease duration, delay in diagnosis, alcohol intake), disease outcome measures (DAS28, fatigue, sleep, HAQ, EQ-5D, radiographic damage, surgery), medications, and adverse events were assessed. To analyze the factors associated with moderate to severe disease activity (DAS 28_ESR ≥3.2) among the 3 groups, logistic regression analysis was used.

Results 1. Latent Mycobacterium Tuberculosis in Korean Patients with Rheumatic Disease 1) Factors Influencing Discrepancies Between QFT-GIT and TST The positivity of QFT-GIT was higher in RA than AS or JRA (30.2%, 16.2%, and 3.4%, respectively). In contrast, TST positivity was highest in AS compared to RA and JRA (45.5%, 28.2%, and 17.2%, respectively). The agreement between two tests was low in all patients (κ = 0.285). The only predictor of a discrepancy between two tests was older age. Factors associated with discordant QFT-GIT-negative/TST-positive results were female (OR=2.33, CI 1.11-4.89) and AS (OR=3.12, CI 1.44-6.79), while discordant QFT-GIT-positive/TST-negative result was associated with glucocorticoid use (OR=2.44, CI 1.24-4.81).

2) Evaluation of the Usefulness of QFT-GIT and TST for Detection of LTBI A total of 5 patients developed TB after initiation of biologics according to the screening guideline of LTBI. Among them, extra-pulmonary TB occurred in 3 patients. TB occurred in 3 patients among those tested only by TST, did not occur among those tested only by QFT-GIT, and TB occurred in 2 patients among those who tested both by QFT-GIT and TST. Some patients did not comply with LTBI prophylactic strategy. TB occurred in 2 patients according to LTBI prophylactic strategy. TB incidence in the group that received both QFT-GIT and TST was 151.05 / 100,000 person-years and that in the group that received only TST was 169.78 / 100,000 person-years among the patients who complied with LTBI prophylactic strategy.

2. Hepatitis B in Korean Patients with Rheumatic Disease 1) Treatment and Outcomes of Rheumatoid Arthritis Patients with Hepatitis B A total of 871 patients were assessed. The number of HBsAg-positive and HBcAb-positive patients were 48 (5.5%) and 372 (42.7%), respectively. HBcAb-positive groups were significantly older (56.3±10.8 vs 52.5±9.0 in HBsAg-positive group and 51.3±13.3 in negative group, p<0.01) and had longer disease duration (8.4±7.7 vs 7.7±6.0 in HBsAg-positive group and 7.8±7.2 in control group, p=0.49). Methotrexate and biologics use were significantly lower in HBsAg-positive group, while hydroxychloroquine, sulfasalazine, tacrolimus, and steroids use were significantly higher. There was no significant difference in disease outcome measures between the groups, except for significantly increased radiographic damage in HBcAb group (79.6% vs 70.8% in HBsAg-positive group and 72.5% in negative group, p=0.048). HBsAg-positive group had significantly more adverse events (52.1%) compared to HBcAb-positive group (29.3%) and control group (32.8%). The factors associated with disease activity (DAS 28 ≥3.2) were not observed in HBsAg-positive group. Female (OR 2.74, 95% CI 1.45 to 5.18) and age of disease onset (OR 2.29, 95% CI 1.17 to 4.46) was associated with disease activity (DAS 28 ≥3.2) in HBcAb-positive group.

Conclusion The agreement between QFT-GIT and TST is low; therefore it would be better to perform both tests than to use any one test alone for the detection of LTBI in TB-endemic regions. Female and underlying AS are related to QFT-GIT-negative/TST-positive, and the use of glucocorticoid is associated with QFT-GIT-positive/TST-negative. TB did not occur in patients who received TB prophylaxis by positive results by either only TST strategy or QFT-GIT & TST strategy. And TB incidence in patients who received QFT-GIT and TST prophylactic strategy seems to be lower than that in those who performed only TST prophylactic strategy. However, it was difficult to calculate the significance of this difference or superiority because the observation period was short. And also a prospective analysis of the cost-effectiveness of both tests for LTBI screening to prevent active TB infection during the use of biologics is required. HBsAg-positive patients were treated with significantly more frequently with steroids and less with methotrexate, but there was no significant difference in disease outcome. HBsAg-positive patients had more adverse events but to mention about HBV reactivation, long-term follow up study about the liver function abnormality including HBV DNA level among the RA patients who are positive HBsAg or positive HBcAb is required.