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Giri S, Bhrugumalla S, Shukla A, Gangadhar S, Reddy S, Angadi S, Shinde L, Kale A. Risk of tuberculosis with anti-TNF therapy in Indian patients with inflammatory bowel disease despite negative screening. Arab J Gastroenterol 2025; 26:33-37. [PMID: 38383265 DOI: 10.1016/j.ajg.2024.01.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 08/26/2023] [Accepted: 01/26/2024] [Indexed: 02/23/2024]
Abstract
BACKGROUND AND STUDY AIMS Tuberculosis (TB) is a well-recognized adverse effect associated with using biological therapy to manage various autoimmune conditions. There is a dearth of information about the development of TB after using anti-TNF agents in patients with inflammatory bowel disease (IBD) from TB-endemic countries like India. This study aimed to estimate the risk of TB and its predictors after treatment with anti-TNF agents in patients with IBD. PATIENTS AND METHODS The present study is a retrospective analysis of data of patients with IBD from two tertiary care centers in India receiving anti-TNF therapy. Patients who had undergone chest X-ray, high-resolution computed tomography of the chest, and tuberculin skin test, with a follow-up duration of at least 6 months, were included in the analysis. RESULTS In this multi-center study, 95 patients on anti-TNF agents for IBD (Median age of onset: 27 years, 62.1 % males) were followed up for a median duration of 9 (6-142) months. Among patients with IBD, 79 (83.2 %) had Crohn's disease, and 16 (16.8 %) had ulcerative colitis. Infliximab was the commonest biological, used in 82.1 % of cases, followed by adalimumab (17.9 %). On follow-up, 8.4 % (8/95) of the patients developed TB, among which the majority had extrapulmonary tuberculosis (5/8). On multivariate analysis, the duration of biological (Odds ratio: 1.047, 95 % confidence interval 1.020-1.075; p = 0.001) use was the only independent predictor of the development of TB with biologicals. CONCLUSION Among Indian patients with IBD, there is a high risk of TB with anti-TNF agents, which increases with the duration of therapy. The current methods for latent TB screening in Indians are ineffective, and predicting TB after initiating biological therapy is difficult.
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Affiliation(s)
- Suprabhat Giri
- Department of Gastroenterology, Nizam's Institute of Medical Sciences, Hyderabad, India
| | - Sukanya Bhrugumalla
- Department of Gastroenterology, Nizam's Institute of Medical Sciences, Hyderabad, India
| | - Akash Shukla
- Department of Gastroenterology, Seth GS Medical College and KEM Hospital, Mumbai, India
| | - Sagar Gangadhar
- Department of Gastroenterology, Nizam's Institute of Medical Sciences, Hyderabad, India
| | - Srujan Reddy
- Department of Gastroenterology, Nizam's Institute of Medical Sciences, Hyderabad, India
| | - Sumaswi Angadi
- Department of Gastroenterology, Nizam's Institute of Medical Sciences, Hyderabad, India
| | - Leela Shinde
- Department of Gastroenterology, Seth GS Medical College and KEM Hospital, Mumbai, India
| | - Aditya Kale
- Department of Gastroenterology, Seth GS Medical College and KEM Hospital, Mumbai, India.
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Feakins RM. Inflammatory disorders of the large intestine. MORSON AND DAWSON'S GASTROINTESTINAL PATHOLOGY 2024:709-857. [DOI: 10.1002/9781119423195.ch35] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Yu Y, Yu Q, Shen KR, Xu DT, Hu W, Li SY, Cai QS, Chen Y. New-onset extrapulmonary tuberculosis in negative latent tuberculosis infection screening patients with Crohn's disease under anti-TNF therapy in a tuberculosis-endemic region: A case series. J Dig Dis 2023; 24:369-375. [PMID: 37464547 DOI: 10.1111/1751-2980.13206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 07/16/2023] [Accepted: 07/17/2023] [Indexed: 07/20/2023]
Affiliation(s)
- Yue Yu
- Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Qiao Yu
- Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Ke Ren Shen
- Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Ding Ting Xu
- Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Wen Hu
- Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Shu Yan Li
- Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Qing Shan Cai
- Zhengjiang Tuberculosis Diagnosis and Treatment Center, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang Province, China
| | - Yan Chen
- Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
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Jahnich N, Arkwright PD. Regional risk of tuberculosis and viral hepatitis with tumor necrosis factor-alpha inhibitor treatment: A systematic review. Front Pharmacol 2023; 14:1046306. [PMID: 36744250 PMCID: PMC9894886 DOI: 10.3389/fphar.2023.1046306] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 01/05/2023] [Indexed: 01/21/2023] Open
Abstract
Background: TNFα inhibitors are regularly used to treat autoimmune diseases. Tuberculosis (TB) and viral hepatitis B are considered potential infectious complications, and screening and surveillance are therefore recommended. Current guidelines do not take into account regional differences in endemicity of these infections. Methods: A systematic literature review of TB and viral hepatitis in patients receiving TNFα-inhibitors was performed, searching in PubMed, Embase, MEDLINE and Web of Science databases. Studies were selected against predefined eligibility criteria and assessed using the Newcastle-Ottawa scale. The number of TB and viral hepatitis cases/1,000 TNFα-inhibitor patients were evaluated, and regional variation compared. Results: 105 observational studies involving over 140,000 patients were included. Overall, 1% of patients developed TB or viral hepatitis B. TB cases/1,000 TNFα-inhibitor patients were 4-fold higher in Asia, Africa, and South America than in Europe, North America, and Australasia where only 0%-0.4% of patients developed TB. Hepatitis B cases/1,000 patients were over 15-fold higher in countries with high prevalence (China, Taiwan, South Korea, Thailand) compared with low prevalence (p < 0.00001) where only 0.4% of patients developed hepatitis B. Only three of 143 patients developed viral hepatitis C, and there was insufficient data to allow regional sub-analysis. Conclusion: TB and viral hepatitis B infections in patients treated with TNFα inhibitors are largely confined to countries with high prevalence of these infections. As only 1/2,500 patients in low prevalence countries treated with TNFα inhibitors develop TB or viral hepatitis B, we suggest an individualized, risk-based approach, rather than universal screening for all patients.
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Affiliation(s)
| | - Peter D. Arkwright
- Lydia Becker Institute of Immunology and Inflammation, Manchester Incubator Building, University of Manchester, Manchester, United Kingdom
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Kumar P, Vuyyuru SK, Kante B, Sahu P, Goyal S, Madhu D, Jain S, Ranjan MK, Mundhra S, Golla R, Singh M, Virmani S, Gupta A, Yadav N, Kalaivani M, Sharma R, Das P, Makharia G, Kedia S, Ahuja V. Stringent screening strategy significantly reduces reactivation rates of tuberculosis in patients with inflammatory bowel disease on anti-TNF therapy in tuberculosis endemic region. Aliment Pharmacol Ther 2022; 55:1431-1440. [PMID: 35229906 DOI: 10.1111/apt.16839] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 12/10/2022] [Accepted: 02/07/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND Anti-tumor necrosis factor (anti-TNF) therapy use in patients with inflammatory bowel disease (IBD) leads to an increased risk of tuberculosis (TB) reactivation despite latent tuberculosis (LTB) screening, especially in TB endemic regions. AIM We evaluated the effect of stringent screening strategy and LTB prophylaxis on TB reactivation. METHODS We performed an ambispective comparison between patients who received anti-TNF therapy after January 2019 (late cohort) and between Jan 2005 and Jan 2019 (early cohort). Late cohort patients were subjected to stringent screening criteria which included all: history of past TB/recent contact with active TB, chest X-ray, CT (computed tomography) chest, IGRA (interferon-gamma release assay), TST (tuberculin skin test), and if any positive were given chemoprophylaxis. A cohort comparison was done to evaluate for risk reduction of TB following the stringent screening strategy. RESULTS One hundred seventy-one patients (63: ulcerative colitis/108: Crohn's disease, mean age diagnosis: 28.5 ± 13.4 years, 60% males, median follow-up duration after anti-TNF: 33 months [interquartile range: 23-57 months]) were included. Among the 112 in the early cohort, 29 (26%) underwent complete TB screening, 22 (19.6%) had LTB, 10 (9%) received chemoprophylaxis, and 19 (17%) developed TB. In comparison, in the late cohort, 100% of patients underwent complete TB screening, 26 (44%) had LTB, 23 (39%) received chemoprophylaxis, and only 1(1.7%) developed TB (p < 0.01). On survival analysis, patients in early cohort had a higher probability of TB reactivation compared with the late cohort (HR: 14.52 (95% CI: 1.90-110.61 [p = 0.01]) after adjusting for gender, age at anti-TNF initiation, concomitant immunosuppression, anti-TNF doses, and therapy escalation. CONCLUSION The high risk of TB reactivation with anti-TNF therapy in TB endemic regions can be significantly mitigated with stringent LTB screening and chemoprophylaxis.
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Affiliation(s)
- Peeyush Kumar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Sudheer K Vuyyuru
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Bhaskar Kante
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Pabitra Sahu
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Sandeep Goyal
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Deepak Madhu
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Saransh Jain
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Mukesh Kumar Ranjan
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Sandeep Mundhra
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Rithvik Golla
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Mukesh Singh
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Shubi Virmani
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Anvita Gupta
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Nidhi Yadav
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Mani Kalaivani
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
| | - Raju Sharma
- Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India
| | - Prasenjit Das
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Govind Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Saurabh Kedia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
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Lee JY, Oh K, Hong HS, Kim K, Hong SW, Park JH, Hwang SW, Yang DH, Ye BD, Byeon JS, Myung SJ, Yang SK, Lee HS, Jo KW, Park SH. Risk and characteristics of tuberculosis after anti-tumor necrosis factor therapy for inflammatory bowel disease: a hospital-based cohort study from Korea. BMC Gastroenterol 2021; 21:390. [PMID: 34670529 PMCID: PMC8527666 DOI: 10.1186/s12876-021-01973-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Accepted: 10/07/2021] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND Anti-tumor necrosis factor (TNF) treatment for inflammatory bowel disease (IBD) increases the risk of tuberculosis (TB) infection. In the present study, we analyzed the clinical characteristics and risks of TB in Korean patients with IBD who received anti-TNF treatment. METHODS The study included patients with IBD who were treated using anti-TNF agents between January 2001 and June 2018 at the Asan Medical Center. Overall, 1434 patients with ulcerative colitis or Crohn's disease were enrolled. We calculated the incidence of active TB infection after anti-TNF treatment and compared the clinical characteristics of the TB group with those of the non-TB group. RESULTS Twenty-one patients (1.46%) developed active TB infection, and the incidence rate of active TB was 366.73 per 100,000 person-years. In total, 198 patients (14.9%) were positive for latent tuberculosis infection (LTBI), of whom only eight (4%) did not complete LTBI treatment. The age at which the anti-TNF therapy was started was significantly higher in the TB group than in the non-TB group (HR 1.041, 95% CI 1.014-1.069, p = 0.002), and as age increased, so did the incidence rate of active TB infection (linearity p < 0.001). There was no significant difference in the incidence rate of LTBI between the TB and non-TB groups (HR 0.896, 95% CI 0.262-3.066, p = 0.862). CONCLUSIONS In patients with IBD, the incidence rate of TB increased with age at anti-TNF therapy initiation. Active treatment of LTBI may lower the incidence of TB in patients with IBD who are to undergo anti-TNF therapy.
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Affiliation(s)
- Jae Yong Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Kyunghwan Oh
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Hee Seung Hong
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Kyuwon Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Seung Wook Hong
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Jin Hwa Park
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Sung Wook Hwang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Dong-Hoon Yang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Byong Duk Ye
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Jeong-Sik Byeon
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Seung-Jae Myung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Suk-Kyun Yang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Ho-Su Lee
- Department of Biochemistry, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Kyung-Wook Jo
- Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.
| | - Sang Hyoung Park
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.
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Shin A, Lee YJ, Lee EB, Song YW, Kim SC, Kang EH. Tuberculosis risk with biologics by screening-guided preventive strategy in rheumatoid arthritis under intermediate tuberculosis burden. Rheumatology (Oxford) 2021; 60:2755-2764. [PMID: 33188421 DOI: 10.1093/rheumatology/keaa702] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 09/20/2020] [Indexed: 11/14/2022] Open
Abstract
OBJECTIVES We aimed to compare tuberculosis (TB) risk during biologics treatment between patients with RA who did (prophylaxis) and did not (non-prophylaxis) undergo chemoprophylaxis following pre-biologic latent TB screening in Korea of an intermediate TB burden. METHODS Using the 2002-16 Korea National Health Insurance database, we conducted a cohort study examining TB risk, defined by International Classification of Diseases Tenth Revision codes plus anti-TB drugs, among RA patients initiating a biologic drug with and without chemoprophylaxis after screening triage for latent TB. To control baseline confounding, we used propensity score-based fine stratification (PSS) and weighting. Cox proportional hazards models estimated hazard ratios and 95% CIs comparing TB risk between the prophylaxis vs non-prophylaxis groups. RESULTS The PSS-weighted study cohort (mean age 57.0 years; 81.3% female) included 2249 and 7225 RA patients in the prophylaxis and non-prophylaxis groups, respectively. During 2.42 years of biologics treatment, 118 patients developed TB with the incidence rate per 100 person-years of 0.33 in the prophylaxis and 0.63 in the non-prophylaxis groups. The PSS-weighted hazard ratio (95% CI) for TB associated with the prophylaxis was 0.52 (0.32, 0.86). During the follow-up time, the incidence rate of TB remained consistently low in the prophylaxis group but it was highest in the first year, then time-dependently declined in the non-prophylaxis group. CONCLUSION This population-based cohort study warns that the current screening-based preventive strategy generates a substantially higher TB risk after biologics initiation among screening-negative patients compared with screening-positive patients receiving chemoprophylaxis, when the background TB burden is not low.
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Affiliation(s)
- Anna Shin
- Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yun Jong Lee
- Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Eun Bong Lee
- Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Yeong Wook Song
- Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Seoyoung C Kim
- Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA, USA.,Division of Pharmacoepidemiology & Pharmacoeconomics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Eun Ha Kang
- Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
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Iba A, Tomio J, Yamana H, Sugiyama T, Yoshiyama T, Kobayashi Y. Tuberculosis screening and management of latent tuberculosis infection prior to biologic treatment in patients with immune-mediated inflammatory diseases: A longitudinal population-based analysis using claims data. Health Sci Rep 2020; 3:e216. [PMID: 33336081 PMCID: PMC7731986 DOI: 10.1002/hsr2.216] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 11/10/2020] [Accepted: 11/12/2020] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND AND AIM Screening for tuberculosis before treating with biologic agents is recommended in patients with immune-mediated inflammatory diseases (IMIDs). We conducted this study to identify adherence to the recommended practice in a real-world setting in Japan. METHODS We used a community-based insurance claims database in a city in the Greater Tokyo Area in Japan. Between July 2012 and January 2019, we enrolled patients with IMIDs in the age range 15 to 74 years who had initiated biologic therapy. Tuberculosis screening was defined as (a) interferon-γ release assay and/or a tuberculin skin test (IGRA/TST) and (b) IGRA/TST and X-ray and/or CT scan (X-ray/CT) within 2 months before starting biologic agents. We analyzed the proportions of patients who underwent tuberculosis screening and their association with the patient- and treatment-related factors and treatment for latent tuberculosis infection (LTBI). RESULTS Of 421 patients presumed to have initiated biologic therapy, 202 (48%) underwent IGRA/TST and 169 (40%) underwent IGRA/TST and X-ray/CT. Patients aged 65 to 74 years were more likely to undergo tuberculosis screening than those aged 45 to 64 years. Compared to infliximab, IGRA/TST was less frequently performed in patients treated with etanercept, adalimumab, golimumab, abatacept, and tocilizumab. Treatment for LTBI was provided to 67 (16%) patients. Proportions of patients receiving LTBI treatment did not significantly differ according to the screening status. CONCLUSION There was low adherence to the recommendations for tuberculosis screening and prophylactic treatment before biologic therapy. It is necessary to continue alerting clinical practitioners to the importance of screening for tuberculosis and treatment for LTBI.
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Affiliation(s)
- Arisa Iba
- Department of Public HealthGraduate School of Medicine, The University of TokyoTokyoJapan
| | - Jun Tomio
- Department of Public HealthGraduate School of Medicine, The University of TokyoTokyoJapan
| | - Hayato Yamana
- Department of Health Services ResearchGraduate School of Medicine, The University of TokyoTokyoJapan
| | - Takehiro Sugiyama
- Diabetes and Metabolism Information CenterResearch Institute, National Center for Global Health and MedicineTokyoJapan
- Institute for Global Health Policy Research, Bureau of International Health CooperationNational Center for Global Health and MedicineTokyoJapan
- Department of Health Services Research, Faculty of MedicineUniversity of TsukubaIbarakiJapan
| | - Takashi Yoshiyama
- Research Institute of TuberculosisJapan Anti Tuberculosis AssociationTokyoJapan
| | - Yasuki Kobayashi
- Department of Public HealthGraduate School of Medicine, The University of TokyoTokyoJapan
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9
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Fortes FML, Sorte NB, Mariano VD, Andrade LD, Oliveira FA, Santos MCA, Santos CIND, Passos CA, Pacheco MP, Surlo VC, Almeida NPD, Fontes JAM, Pimentel AM, Rocha R, Santana GO. Active tuberculosis in inflammatory bowel disease patients under treatment from an endemic area in Latin America. World J Gastroenterol 2020; 26:6993-7004. [PMID: 33311945 PMCID: PMC7701941 DOI: 10.3748/wjg.v26.i44.6993] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 11/05/2020] [Accepted: 11/14/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND There has been an increase in cases of inflammatory bowel disease (IBD) in recent years. There is also greater access and availability of immunosuppressive and biological agents, which increase the risk of opportunistic infection despite improving the quality of life and promoting mucosal healing. Tuberculosis (TB) remains a public health problem, and it has a high incidence in several countries. Therefore, knowledge of the risk of developing TB in patients with IBD is important. AIM To evaluate the risk of active TB in patients with IBD under treatment from an endemic area in Latin America. METHODS A standard questionnaire included demographic variables, clinical aspects of IBD disease, history of active TB during treatment, active TB characteristics and evolution, initial screening and results and time from the start of anti-tumor necrosis factor alpha (TNFα) to TB development. RESULTS Azathioprine, anti-TNFα and the combination of these two drugs were associated with a higher risk of active TB incidence. The TNFα blockers increased the relative risk of developing active TB compared to other treatments. All four multivariable models showed that the use of TNFα blockers alone or in combination with azathioprine was an important risk factor for the incidence of active TB. After adjustment for sex, age, type of IBD and latent TB, anti-TNFα with azathioprine increased the relative risk to 17.8 times more than conventional treatment. Late TB, which was diagnosed 3 mo after the start of anti-TNFα, was the most frequent. CONCLUSION Treatment with anti-TNFα increased the risk of active TB in IBD patients from an endemic area in Latin America. This risk was increased when anti-TNFα was combined with azathioprine. The time from the beginning of the treatment to the active TB diagnosis suggests a new TB infection.
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Affiliation(s)
- Flora Maria Lorenzo Fortes
- Pharmaceutical Sciences Pos-graduation Program, State University of Bahia, Salvador, BA 40460-120, Brazil
- Outpatient Gastroenterology Unit, General Hospital Roberto Santos, Salvador, BA 40286-901, Brazil
| | - Ney Boa Sorte
- Pharmaceutical Sciences Pos-graduation Program, State University of Bahia, Salvador, BA 40460-120, Brazil
- Life Sciences Department, State University of Bahia, Salvador, BA 41150-000, Brazil
| | - Victor D Mariano
- Life Sciences Department, State University of Bahia, Salvador, BA 41150-000, Brazil
| | - Laíla D Andrade
- Department of Medicine, FTC University, Salvador, BA 41741-590, Brazil
| | - Fernanda A Oliveira
- Life Sciences Department, State University of Bahia, Salvador, BA 41150-000, Brazil
| | - Monique CA Santos
- Life Sciences Department, State University of Bahia, Salvador, BA 41150-000, Brazil
| | | | - Catharina A Passos
- Life Sciences Department, State University of Bahia, Salvador, BA 41150-000, Brazil
| | - Mila P Pacheco
- Pharmaceutical Sciences Pos-graduation Program, State University of Bahia, Salvador, BA 40460-120, Brazil
| | - Valdiana C Surlo
- Outpatient Gastroenterology Unit, General Hospital Roberto Santos, Salvador, BA 40286-901, Brazil
| | - Neogélia P de Almeida
- Outpatient Gastroenterology Unit, General Hospital Roberto Santos, Salvador, BA 40286-901, Brazil
| | - Jaciane AM Fontes
- Outpatient Gastroenterology Unit, General Hospital Roberto Santos, Salvador, BA 40286-901, Brazil
| | - Andréa M Pimentel
- Outpatient Gastroenterology Unit, General Hospital Roberto Santos, Salvador, BA 40286-901, Brazil
| | - Raquel Rocha
- Department of Sciences of Nutrition, School of Nutrition, Federal University of Bahia, Salvador, BA 41701-035, Brazil
| | - Genoile Oliveira Santana
- Pharmaceutical Sciences Pos-graduation Program, State University of Bahia, Salvador, BA 40460-120, Brazil
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Noh H, Jang J, Kwon S, Cho SY, Jung WS, Moon SK, Park JM, Ko CN, Kim H, Park SU. The Impact of Korean Medicine Treatment on the Incidence of Parkinson's Disease in Patients with Inflammatory Bowel Disease: A Nationwide Population-Based Cohort Study in South Korea. J Clin Med 2020; 9:2422. [PMID: 32731605 PMCID: PMC7463832 DOI: 10.3390/jcm9082422] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 07/17/2020] [Accepted: 07/25/2020] [Indexed: 12/16/2022] Open
Abstract
We aimed to investigate the association between Korean medicine (KM) treatment and the risk of Parkinson's Disease (PD) in patients with inflammatory bowel disease (IBD) in South Korea. This study analyzed data from the National Health Insurance Service-Senior cohort in South Korea. The 1816 IBD patients enrolled in the analysis comprised 411 who received only conventional treatment (monotherapy group) and 1405 who received both conventional and KM treatments (integrative therapy group). The risk of PD in patients with IBD was significantly lower in the integrative therapy group than in the monotherapy group after adjusting for confounding variables (adjusted hazard ratio (HR), 0.56; 95% confidence interval (CI) = 0.34-0.92). In the mild Charlson Comorbidity Index (CCI) group, the risk of PD in patients with IBD in the integrative therapy group was 0.39 times lower (adjusted HR, 95% CI = 0.20-0.77) than that in the monotherapy group. However, there was no significant difference in the risk of PD in patients with IBD between the integrative therapy and monotherapy groups among individuals with severe CCI (adjusted HR, 0.90; 95% CI = 0.41-1.96). IBD patients are at a decreased risk of PD when they receive integrative therapy. KM treatment may prevent PD in IBD patients.
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Affiliation(s)
- Hyeonseok Noh
- Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea; (H.N.); (S.K.); (S.-Y.C.); (W.-S.J.); (S.-K.M.); (J.-M.P.); (C.-N.K.)
| | - Jeongju Jang
- Graduate School of Public Health, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea;
| | - Seungwon Kwon
- Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea; (H.N.); (S.K.); (S.-Y.C.); (W.-S.J.); (S.-K.M.); (J.-M.P.); (C.-N.K.)
- Department of Cardiology and Neurology, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea
| | - Seung-Yeon Cho
- Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea; (H.N.); (S.K.); (S.-Y.C.); (W.-S.J.); (S.-K.M.); (J.-M.P.); (C.-N.K.)
- Department of Cardiology and Neurology, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea
| | - Woo-Sang Jung
- Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea; (H.N.); (S.K.); (S.-Y.C.); (W.-S.J.); (S.-K.M.); (J.-M.P.); (C.-N.K.)
- Department of Cardiology and Neurology, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea
| | - Sang-Kwan Moon
- Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea; (H.N.); (S.K.); (S.-Y.C.); (W.-S.J.); (S.-K.M.); (J.-M.P.); (C.-N.K.)
- Department of Cardiology and Neurology, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea
| | - Jung-Mi Park
- Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea; (H.N.); (S.K.); (S.-Y.C.); (W.-S.J.); (S.-K.M.); (J.-M.P.); (C.-N.K.)
- Department of Cardiology and Neurology, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea
| | - Chang-Nam Ko
- Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea; (H.N.); (S.K.); (S.-Y.C.); (W.-S.J.); (S.-K.M.); (J.-M.P.); (C.-N.K.)
- Department of Cardiology and Neurology, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea
| | - Ho Kim
- Department of Public Health Science, Graduate School of Public Health & Institute of Health and Environment, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul 08826, Korea
| | - Seong-Uk Park
- Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea; (H.N.); (S.K.); (S.-Y.C.); (W.-S.J.); (S.-K.M.); (J.-M.P.); (C.-N.K.)
- Department of Cardiology and Neurology, College of Korean Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea
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Castillo-Martínez D, Amezcua-Castillo LM, Granados J, Pineda C, Amezcua-Guerra LM. Is Takayasu arteritis the result of a Mycobacterium tuberculosis infection? The use of TNF inhibitors may be the proof-of-concept to demonstrate that this association is epiphenomenal. Clin Rheumatol 2020; 39:2003-2009. [PMID: 32198554 DOI: 10.1007/s10067-020-05045-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Revised: 02/21/2020] [Accepted: 03/10/2020] [Indexed: 02/07/2023]
Abstract
Although the association between Takayasu arteritis (TA) and latent or active Mycobacterium tuberculosis infection has been suggested for a long time, studies conducted in recent years are challenging this notion. Until recently, the possibility of a pathogenic relationship between TA and tuberculosis (TB) was considered a medical curiosity, but the advent of tumor necrosis factor (TNF) inhibitors as therapy for recalcitrant TA cases, as well as the widespread use of Bacille Calmette-Guérin (BCG) for vaccination purposes, has relocated this association as a top priority issue. In an attempt to define whether both diseases are pathogenically linked or if their association is only epiphenomenal in nature, we conduct a thorough literature search on the development of TB in patients with TA receiving TNF inhibitors. From a total of 13 studies that included 214 patients, the occurrence of TB was observed only in two individuals exposed to infliximab. This frequency of 0.93% is similar to that encountered in patients with other rheumatic diseases exposed to TNF inhibitors. Finally, we propose a novel pathogenic model that could reconcile the epidemiological, clinical, and immunological evidence that links TA and TB, while providing rationality for the use of TNF inhibitors in patients with TA.
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Affiliation(s)
- Diana Castillo-Martínez
- Dermatology Clinic, Hospital General de Zona 32, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | | | - Julio Granados
- Division of Musculoskeletal and Rheumatic Diseases, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico City, Mexico
| | - Carlos Pineda
- Department of Transplantation, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Luis M Amezcua-Guerra
- Department of Immunology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano 1, Sección XVI, 14080 Tlalpan, Mexico City, Mexico. .,Department of Health Care, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico.
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Kedia S, Mouli VP, Kamat N, Sankar J, Ananthakrishnan A, Makharia G, Ahuja V. Risk of Tuberculosis in Patients With Inflammatory Bowel Disease on Infliximab or Adalimumab Is Dependent on the Local Disease Burden of Tuberculosis: A Systematic Review and Meta-Analysis. Am J Gastroenterol 2020; 115:340-349. [PMID: 32032073 DOI: 10.14309/ajg.0000000000000527] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Infliximab (IFX) or adalimumab (ADA) use in patients with inflammatory bowel disease (IBD) leads to increased risk of tuberculosis (TB). This meta-analysis evaluated the factors which determine this risk, with special focus on local TB incidence. METHODS All studies until January 31, 2019, which reported the development of TB in patients with IBD on IFX/ADA, were included after searching PubMed and Embase. Data regarding disease type, number of patients on IFX/ADA, number of patients who developed TB, mean age at IFX/ADA initiation, median duration of development of TB, and latent TB (LTB) were extracted. The details on local TB incidence were obtained from the World Health Organization database, and the studies were stratified into low (<10/100,000), intermediate (10-40/100,000), and high TB burden countries (>40/100,000). Random effect meta-analysis was performed to calculate the overall pooled prevalence and prevalence based on local TB burden. RESULTS Of 130,114 patients (128 studies), 373 developed TB (pooled prevalence: 0.08% [95% confidence interval {CI}: 0.05%-0.10%]). The risk increased with increasing TB burden, pooled prevalence being 0.02% (95% CI: 0.02%-0.03%), 0.21% (95% CI: -0.02% to 0.43%), and 1.59% (95% CI: 1.19%-2.00%) for low, intermediate, and high TB burden countries, respectively. Seventy-three percent of patients who developed TB had no evidence of LTB on screening, the proportion being independent of TB burden. There was no effect of disease or treatment type, study type, gender, age at IFX/ADA initiation, and follow-up duration on TB prevalence. DISCUSSION TB risk in patients with IBD on IFX/ADA depends on the local TB burden and is independent of disease/treatment type.
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Affiliation(s)
- Saurabh Kedia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Venigalla Pratap Mouli
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Nagesh Kamat
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Jeeva Sankar
- Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India
| | - Ashwin Ananthakrishnan
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Govind Makharia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
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QuantiFERON-TB Gold Test Conversion Is Associated with Active Tuberculosis Development in Inflammatory Bowel Disease Patients Treated with Biological Agents: An Experience of a Medical Center in Taiwan. Gastroenterol Res Pract 2019; 2019:7132875. [PMID: 31781198 PMCID: PMC6875270 DOI: 10.1155/2019/7132875] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 10/09/2019] [Indexed: 12/28/2022] Open
Abstract
Taiwan has a lower prevalence of inflammatory bowel disease (IBD) and a higher prevalence of tuberculosis (TB) infection than Western countries. The aim of this study was to investigate the prevalence of latent TB (LTB) and active TB infection in IBD patients treated with biological agents. From January 2000 to September 2018, we retrospectively collected data from IBD patients treated with biological agents at a tertiary referral center. Patients underwent a QuantiFERON-TB Gold test (QFT) to screen for TB infection before and after biological treatment courses. The diagnostic age, sex, body mass index, hepatitis B virus infection, biochemistry profile, treatment regimens, and the results of the QFT were analyzed. Overall, 130 IBD patients who received biological treatment were enrolled. The results of the QFT before biological treatment were determined in 120 patients (92%); of these, 10 were positive (8%), 110 were negative (85%), and 10 were indeterminate (9%). Six patients demonstrated seroconversion after biological treatment, as determined by the QFT. Three patients (2.4%) developed active pulmonary TB after biological treatment. In subgroup analysis, the positive QFT patients had a trend of lower baseline serum C-reactive protein and erythrocyte sedimentation rate levels than the negative QFT group. The present study demonstrates that the prevalence of LTB before and after biological treatment is higher in Taiwan than in most Western countries and similar to other Asian countries. Therefore, screening and monitoring of TB infection are necessary for IBD patients before and during biological treatments in Taiwan.
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15
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Abubakar I, Lalvani A, Southern J, Sitch A, Jackson C, Onyimadu O, Lipman M, Deeks JJ, Griffiths C, Bothamley G, Kon OM, Hayward A, Lord J, Drobniewski F. Two interferon gamma release assays for predicting active tuberculosis: the UK PREDICT TB prognostic test study. Health Technol Assess 2019; 22:1-96. [PMID: 30334521 DOI: 10.3310/hta22560] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND Despite a recent decline in the annual incidence of tuberculosis (TB) in the UK, rates remain higher than in most Western European countries. The detection and treatment of latent TB infection (LTBI) is an essential component of the UK TB control programme. OBJECTIVES To assess the prognostic value and cost-effectiveness of the current two interferon gamma release assays (IGRAs) compared with the standard tuberculin skin test (TST) for predicting active TB among untreated individuals at increased risk of TB: (1) contacts of active TB cases and (2) new entrants to the UK from high-TB-burden countries. DESIGN A prospective cohort study and economic analysis. PARTICIPANTS AND SETTING Participants were recruited in TB clinics, general practices and community settings. Contacts of active TB cases and migrants who were born in high-TB-burden countries arriving in the UK were eligible to take part if they were aged ≥ 16 years. MAIN OUTCOME MEASURES Outcomes include incidence rate ratios comparing the incidence of active TB in those participants with a positive test result and those with a negative test result for each assay, and combination of tests and the cost per quality-adjusted life-year (QALY) for each screening strategy. RESULTS A total of 10,045 participants were recruited between May 2010 and July 2015. Among 9610 evaluable participants, 97 (1.0%) developed active TB. For the primary analysis, all test data were available for 6380 participants, with 77 participants developing active TB. A positive result for TSTa (positive if induration is ≥ 5 mm) was a significantly poorer predictor of progression to active TB than a positive result for any of the other tests. Compared with TSTb [positive if induration is ≥ 6 mm without prior bacillus Calmette-Guérin (BCG) alone, T-SPOT®.TB (Oxford Immunotec Ltd, Oxford, UK), TSTa + T-SPOT.TB, TSTa + IGRA and the three combination strategies including TSTb were significantly superior predictors of progression. Compared with the T-SPOT.TB test alone, TSTa + T-SPOT.TB, TSTb + QuantiFERON® TB Gold In-Tube (QFT-GIT; QIAGEN GmbH, Hilden, Germany) and TSTb + IGRA were significantly superior predictors of progression and, compared with QFT-GIT alone, T-SPOT.TB, TSTa + T-SPOT.TB, TSTa + QFT-GIT, TSTa + IGRA, TSTb + T-SPOT.TB, TSTb + QFT-GIT and TSTb + IGRA were significantly superior predictors of progression. When evaluating the negative predictive performance of tests and strategies, negative results for TSTa + QFT-GIT were significantly poorer predictors of non-progression than negative results for TSTa, T-SPOT.TB and TSTa + IGRA. The most cost-effective LTBI testing strategies are the dual-testing strategies. The cost and QALY differences between the LTBI testing strategies were small; in particular, QFT-GIT, TSTb + T-SPOT.TB and TSTb + QFT-GIT had very similar incremental net benefit estimates. CONCLUSION This study found modest differences between tests, or combinations of tests, in identifying individuals who would go on to develop active TB. However, a two-step approach that combined TSTb with an IGRA was the most cost-effective testing option. IMPLICATIONS FOR PRACTICE AND FUTURE RESEARCH The two-step TSTb strategy, which stratified the TST by prior BCG vaccination followed by an IGRA, was the most cost-effective approach. The limited ability of current tests to predict who will progress limits the clinical utility of tests. The implications of these results for the NHS England/Public Health England national TB screening programme for migrants should be investigated. STUDY REGISTRATION This study is registered as NCT01162265. FUNDING The National Institute for Health Research Health Technology Assessment programme.
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Affiliation(s)
- Ibrahim Abubakar
- Institute for Global Health, University College London, London, UK
| | - Ajit Lalvani
- Tuberculosis Research Centre, National Heart and Lung Institute, Imperial College London, London, UK
| | - Jo Southern
- National Infection Service, Public Health England, London, UK
| | - Alice Sitch
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | | | - Oluchukwu Onyimadu
- Southampton Health Technology Assessment Centre, University of Southampton, Southampton, UK
| | - Marc Lipman
- Respiratory Medicine, University College London, London, UK
| | - Jonathan J Deeks
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Chris Griffiths
- Blizard Institute, Queen Mary University of London, London, UK
| | | | - Onn Min Kon
- Imperial College Healthcare NHS Trust, London, UK
| | - Andrew Hayward
- Institute of Epidemiology and Health Care, University College London, London, UK
| | - Joanne Lord
- Southampton Health Technology Assessment Centre, University of Southampton, Southampton, UK
| | - Francis Drobniewski
- Tuberculosis Research Centre, National Heart and Lung Institute, Imperial College London, London, UK
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Agarwal A, Kedia S, Jain S, Gupta V, Bopanna S, Yadav DP, Goyal S, Mouli VP, Dhingra R, Makharia G, Ahuja V. High risk of tuberculosis during infliximab therapy despite tuberculosis screening in inflammatory bowel disease patients in India. Intest Res 2018; 16:588-598. [PMID: 30301331 PMCID: PMC6223459 DOI: 10.5217/ir.2018.00023] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2018] [Revised: 06/16/2018] [Accepted: 06/25/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND/AIMS The data on the risk of tuberculosis (TB) reactivation with infliximab (IFX) in patients with inflammatory bowel disease (IBD) from TB endemic countries, like India, is limited. The risk of TB reactivation on IFX and its predictors in patients with IBD was assessed. METHODS This retrospective review included consecutive patients with IBD who received IFX, and were on follow-up from January 2005 to November 2017. The data was recorded on age/disease duration, indications for IFX, screening for latent tuberculosis (LTB) before IFX, response to IFX, incidence and duration when TB developed after IFX, and type of TB (pulmonary [PTB]/extra-pulmonary [EPTB]/disseminated). RESULTS Of 69 patients (22 ulcerative colitis/47 Crohn's disease; mean age, 35.6±14.5 years; 50.7% males; median follow-up duration after IFX, 19 months [interquartile range, 5.5-48.7 months]), primary non-response at 8 weeks and secondary loss of response at 26 and 52 weeks were seen in 14.5%, 6% and 15% patients respectively. Prior to IFX, all patients were screened for LTB, 8 (11.6%) developed active TB (disseminated, 62.5%; EPTB, 25%; PTB, 12.5%) after a median of 19 weeks (interquartile range, 14.0-84.5 weeks) of IFX. Of these 8 patients' none had LTB, even when 7 of 8 were additionally screened with contrast-enhanced chest tomography. Though not statistically significant, more patients with Crohn's disease than ulcerative colitis (14.9% vs. 4.5%, P=0.21), and those with past history of TB (25% vs. 9.8%, P=0.21), developed TB. Age, gender, disease duration, or extraintestinal manifestations could not predict TB reactivation. CONCLUSIONS There is an extremely high rate of TB with IFX in Indian patients with IBD. Current screening techniques are ineffective and it is difficult to predict TB after IFX.
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Affiliation(s)
- Ashish Agarwal
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Saurabh Kedia
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Saransh Jain
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Vipin Gupta
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Sawan Bopanna
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Dawesh P Yadav
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Sandeep Goyal
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Venigalla Pratap Mouli
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Rajan Dhingra
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Govind Makharia
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
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Ramos GP, Stroh G, Al-Bawardy B, Faubion WA, Papadakis KA, Escalante P. Outcomes of Treatment for Latent Tuberculosis Infection in Patients With Inflammatory Bowel Disease Receiving Biologic Therapy. Inflamm Bowel Dis 2018; 24:2272-2277. [PMID: 29718223 DOI: 10.1093/ibd/izy133] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND Treatment for latent tuberculosis infection (LTBI) is of particular concern in patients with inflammatory bowel disease (IBD) initiating biologic therapies to prevent tuberculosis (TB) reactivation. This study aimed to evaluate the effectiveness of LTBI treatment in IBD patients receiving biologic therapy. METHODS There was a retrospective review of all IBD patients diagnosed with LTBI following a tuberculin skin test (TST) and/or interferon gamma release assay (IGRA) and who received biologic therapy between 2002 and 2016. The primary outcome was tuberculosis reactivation after completion of LTBI treatment. RESULTS Three-hundred twenty-nine IBD patients were identified, and 35 (27 Crohn's disease; 8 ulcerative colitis) met the study inclusion criteria. The mean age was 38.3 years, and 68.6% were male. The most common LTBI treatment regimen was isoniazid (INH) for 9 months (74%). Biologic therapies used were infliximab (40%), adalimumab (29%), vedolizumab (20%), and certolizumab pegol (11%). Combination therapy with an immunomodulator was administered in 57% of cases. The median time from initiation of LTBI treatment to biologics was 43 days. The mean duration of follow-up was 2.9 years. The estimated median annual risk of TB reactivation without treatment was 0.52% by a prediction formula. Only 1 patient taking adalimumab monotherapy developed reactivation of TB several years after completing 6 months of isoniazid therapy. The estimated TB reactivation rate was 0.98 cases per 100 patient-years of follow-up in our cohort. CONCLUSIONS Treatment for LTBI in patients with IBD treated with biologics is effective but does not eliminate the risk of reactivation. 10.1093/ibd/izy133_video1izy133.video15776720675001.
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Affiliation(s)
- Guilherme P Ramos
- Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Gregory Stroh
- Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Badr Al-Bawardy
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - William A Faubion
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Patricio Escalante
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic Center of Tuberculosis, Mayo Clinic, Rochester, Minnesota, USA
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Thi AA, Abbara A, Bouri S, Collin SM, Wolfson P, Owen L, Buell KG, John L, Hart AL. Challenges in screening for latent tuberculosis in inflammatory bowel disease prior to biologic treatment: a UK cohort study. Frontline Gastroenterol 2018; 9:234-240. [PMID: 30046428 PMCID: PMC6056083 DOI: 10.1136/flgastro-2017-100951] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2017] [Revised: 03/08/2018] [Accepted: 03/20/2018] [Indexed: 02/04/2023] Open
Abstract
OBJECTIVE The aim of this study was to determine the occurrence of latent tuberculosis infections (LTBI) and active TB in a cohort of patients with inflammatory bowel disease (IBD) treated with biologics. We also examined the effects of immunosuppressive drugs on indeterminate interferon-gamma release assays (IGRA) in LTBI screening. DESIGN Retrospective study of patients treated with biologics between March 2007 and November 2015. SETTING St Mark's Hospital, North West London, UK. PATIENTS 732 patients with IBD who were screened for LTBI using either tuberculin skin test or IGRA before starting a biologic treatment. METHODS Retrospective case note review of all patients with IBD who were screened for LTBI prior to initiating biologics. Patients who developed active TB were identified from the London TB register. RESULTS Of 732 patients with IBD, 31 (4.2%) were diagnosed with and treated for LTBI with no significant side effects. Six of 596 patients (1.0%) who received biologic treatment developed active TB. There was a higher proportion of indeterminate IGRA in the immunosuppressive medication group compared with the non-immunosuppressive group (33% (59/181) compared with 9% (6/66), p<0.001). The combination of steroids and thiopurines had the highest proportion of indeterminate IGRA (64%, 16/25). High and low doses of steroids were equally likely to result in an indeterminate IGRA result (67% (8/12) and 57% (4/7), respectively). CONCLUSIONS This study highlights the challenges of LTBI screening prior to commencing biologic therapy and demonstrates the risk of TB in patients who have been screened and who are receiving prolonged and continuing doses of antitumour necrosis factor.
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Affiliation(s)
- Aye Aye Thi
- Inflammatory Bowel Disease Unit, St Mark’s Hospital, London, UK
| | - Aula Abbara
- Department of Infectious Diseases, Northwick Park Hospital, London, UK
| | - Sonia Bouri
- Inflammatory Bowel Disease Unit, St Mark’s Hospital, London, UK
| | - Simon M Collin
- Bristol Medical School, University of Bristol, Bristol, UK
| | - Paul Wolfson
- Inflammatory Bowel Disease Unit, St Mark’s Hospital, London, UK
| | - Leah Owen
- Inflammatory Bowel Disease Unit, St Mark’s Hospital, London, UK
| | - Kevin G Buell
- Department of Primary Care and Public Health, Imperial College London, London, UK
| | - Laurence John
- Department of Infectious Diseases, Northwick Park Hospital, London, UK
| | - Ailsa L Hart
- Inflammatory Bowel Disease Unit, St Mark’s Hospital, London, UK
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Park DI, Hisamatsu T, Chen M, Ng SC, Ooi CJ, Wei SC, Banerjee R, Hilmi IN, Jeen YT, Han DS, Kim HJ, Ran Z, Wu K, Qian J, Hu PJ, Matsuoka K, Andoh A, Suzuki Y, Sugano K, Watanabe M, Hibi T, Puri AS, Yang SK. Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 1: risk assessment. Intest Res 2018; 16:4-16. [PMID: 29422793 PMCID: PMC5797269 DOI: 10.5217/ir.2018.16.1.4] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2017] [Revised: 10/12/2017] [Accepted: 10/13/2017] [Indexed: 01/18/2023] Open
Abstract
Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from 9 Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 1 of the statements comprised 2 parts: risk of TB infection Recommendaduring anti-TNF therapy, and screening for TB infection prior to commencing anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.
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Affiliation(s)
- Dong Il Park
- Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Tadakazu Hisamatsu
- The Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan
| | - Minhu Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Siew Chien Ng
- Department of Medicine and Therapeutics, Institute of Digestive Disease, LKS Institute of Health Science, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Choon Jin Ooi
- Gleneagles Medical Centre and Duke-NUS Medical School, Singapore, Singapore
| | - Shu Chen Wei
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Rupa Banerjee
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Ida Normiha Hilmi
- Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Yoon Tae Jeen
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Dong Soo Han
- Department of Internal Medicine, Hanyang University Guri Hospital, Guri, Korea
| | - Hyo Jong Kim
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
| | - Zhihua Ran
- Department of Gastroenterology, Shanghai Jiao Tong University, Shanghai, China
| | - Kaichun Wu
- Department of Gastroenterology, Fourth Military Medical University, Xi'an, China
| | - Jiaming Qian
- Department of Gastroenterology, Peking Union Medical College, Beijing, China
| | - Pin-Jin Hu
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Katsuyoshi Matsuoka
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Akira Andoh
- Department of Gastroenterology, Shiga University, Otsu, Japan
| | - Yasuo Suzuki
- Department of Internal Medicine, Toho University, Sakura, Japan
| | - Kentaro Sugano
- Department of Medicine, Jichi Medical University, Shimotsuke, Japan
| | - Mamoru Watanabe
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Toshifumi Hibi
- Center for Advanced IBD Research and Treatment, Kitasato University, Tokyo, Japan
| | - Amarender S Puri
- Department of Gastroenterology, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi, India
| | - Suk-Kyun Yang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Park DI, Hisamatsu T, Chen M, Ng SC, Ooi CJ, Wei SC, Banerjee R, Hilmi IN, Jeen YT, Han DS, Kim HJ, Ran Z, Wu K, Qian J, Hu PJ, Matsuoka K, Andoh A, Suzuki Y, Sugano K, Watanabe M, Hibi T, Puri AS, Yang SK. Asian Organization for Crohn's and Colitis and Asian Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 1: Risk assessment. J Gastroenterol Hepatol 2018; 33:20-29. [PMID: 29023903 DOI: 10.1111/jgh.14019] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Accepted: 10/05/2017] [Indexed: 12/12/2022]
Abstract
Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asian Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection, and prevention of latent TB infection and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from nine Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 1 of the statements comprised two parts: (i) risk of TB infection during anti-TNF therapy and (ii) screening for TB infection prior to commencing anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.
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Affiliation(s)
- Dong Ii Park
- Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, Seoul, Korea
| | - Tadakazu Hisamatsu
- The Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan
| | - Minhu Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Siew Chien Ng
- Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong
| | - Choon Jin Ooi
- Gleneagles Medical Centre and Duke-NUS Medical School, Singapore
| | - Shu Chen Wei
- Department of Internal Medicine, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Rupa Banerjee
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Ida Normiha Hilmi
- Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Yoon Tae Jeen
- Department of Internal Medicine, Korea University, Seoul, Korea
| | - Dong Soo Han
- Department of Internal Medicine, Hanyang University Guri Hospital, Gyunggi, Korea
| | - Hyo Jong Kim
- Department of Internal Medicine, Kyung Hee University, Seoul, Korea
| | - Zhihua Ran
- Department of Gastroenterology, Shanghai Jiao Tong University, Shanghai, China
| | - Kaichun Wu
- Department of Gastroenterology, Fourth Military Medical University, Xi'an, China
| | - Jiaming Qian
- Department of Gastroenterology, Peking Union Medical College, Beijing, China
| | - Pin-Jin Hu
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Katsuyoshi Matsuoka
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Akira Andoh
- Department of Gastroenterology, Shiga University, Otsu, Japan
| | - Yasuo Suzuki
- Department of Internal Medicine, Toho University, Tokyo, Japan
| | - Kentaro Sugano
- Department of Medicine, Jichi Medical University, Shimotsuke, Japan
| | - Mamoru Watanabe
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Toshifumi Hibi
- Center for Advanced IBD Research and Treatment, Kitasato University, Tokyo, Japan
| | - Amarender S Puri
- Department of Gastroenterology, GB Pant Institute of Postgraduate Medical Education and Research, New Delhi, India
| | - Suk-Kyun Yang
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
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21
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Polymorphisms in the SP110 and TNF-α Gene and Susceptibility to Pulmonary and Spinal Tuberculosis among Southern Chinese Population. DISEASE MARKERS 2017; 2017:4590235. [PMID: 29430075 PMCID: PMC5752994 DOI: 10.1155/2017/4590235] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/06/2017] [Accepted: 12/10/2017] [Indexed: 01/15/2023]
Abstract
Objective To investigate the association of single-nucleotide polymorphisms (SNPs) in SP110 gene and TNF-α gene among pulmonary TB (PTB) and spinal TB (STB) patients. Methods In a total of 190 PTB patients, 183 STB patients were enrolled as the case group and 362 healthy individuals at the same geographical region as the control group. The SP110 SNPs (rs722555 and rs1135791) and the promoter -308G>A (rs1800629) and -238G>A (rs361525) polymorphisms in TNF-α were genotyped. Results. TNF-α -238G>A polymorphism was involved in susceptibility to STB, but not to PTB. The TNF-α -238 A allele was a protective factor against STB (A versus G: OR [95% CI] = 0.331 [0.113–0.972], P = 0.044). Furthermore, the presence of the -238 A allele was considered a trend to decrease the risk of STB (AG versus GG: P = 0.062, OR [95% CI] = 0.352 [0.118–1.053]; AA + AG versus GG: P = 0.050, OR [95CI%] = 0.335 [0.113–0.999]). However, SP110 SNPs (rs722555 and rs1135791) and TNF-α -308G>A (rs1800629) showed no association with PTB and STB in all genetic models. Conclusion The TNF-α -238 A allele appeared a protective effect against STB, whereas the SP110 SNPs (rs722555 and rs1135791) and TNF-α -308G>A (rs1800629) showed no association with susceptibility to PTB and STB patients in southern China.
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Zhou Y, Du J, Hou HY, Lu YF, Yu J, Mao LY, Wang F, Sun ZY. Application of ImmunoScore Model for the Differentiation between Active Tuberculosis and Latent Tuberculosis Infection as Well as Monitoring Anti-tuberculosis Therapy. Front Cell Infect Microbiol 2017; 7:457. [PMID: 29164066 PMCID: PMC5670161 DOI: 10.3389/fcimb.2017.00457] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2017] [Accepted: 10/12/2017] [Indexed: 01/17/2023] Open
Abstract
Tuberculosis (TB) is a leading global public health problem. To achieve the end TB strategy, non-invasive markers for diagnosis and treatment monitoring of TB disease are urgently needed, especially in high-endemic countries such as China. Interferon-gamma release assays (IGRAs) and tuberculin skin test (TST), frequently used immunological methods for TB detection, are intrinsically unable to discriminate active tuberculosis (ATB) from latent tuberculosis infection (LTBI). Thus, the specificity of these methods in the diagnosis of ATB is dependent upon the local prevalence of LTBI. The pathogen-detecting methods such as acid-fast staining and culture, all have limitations in clinical application. ImmunoScore (IS) is a new promising prognostic tool which was commonly used in tumor. However, the importance of host immunity has also been demonstrated in TB pathogenesis, which implies the possibility of using IS model for ATB diagnosis and therapy monitoring. In the present study, we focused on the performance of IS model in the differentiation between ATB and LTBI and in treatment monitoring of TB disease. We have totally screened five immunological markers (four non-specific markers and one TB-specific marker) and successfully established IS model by using Lasso logistic regression analysis. As expected, the IS model can effectively distinguish ATB from LTBI (with a sensitivity of 95.7% and a specificity of 92.1%) and also has potential value in the treatment monitoring of TB disease.
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Affiliation(s)
- Yu Zhou
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Juan Du
- Wuhan Pulmonary Hospital, Wuhan Institute for Tuberculosis Control, Wuhan, China
| | - Hong-Yan Hou
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yan-Fang Lu
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jing Yu
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Li-Yan Mao
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Feng Wang
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zi-Yong Sun
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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23
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Tomio J, Yamana H, Matsui H, Yamashita H, Yoshiyama T, Yasunaga H. Tuberculosis screening prior to anti‐tumor necrosis factor therapy among patients with immune‐mediated inflammatory diseases in Japan: a longitudinal study using a large‐scale health insurance claims database. Int J Rheum Dis 2017; 20:1674-1683. [DOI: 10.1111/1756-185x.13190] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Affiliation(s)
- Jun Tomio
- Department of Public HealthGraduate School of MedicineThe University of TokyoTokyo Japan
| | - Hayato Yamana
- Department of Clinical Epidemiology and Health Economics Graduate School of Medicine The University of TokyoTokyoJapan
- Health and Sanitation Department, Bunkyo City Tokyo Japan
| | - Hiroki Matsui
- Department of Clinical Epidemiology and Health Economics Graduate School of Medicine The University of TokyoTokyoJapan
| | - Hiroyuki Yamashita
- Division of Rheumatic Diseases National Center for Global Health and MedicineTokyoJapan
| | - Takashi Yoshiyama
- Research Institute of Tuberculosis Tokyo Japan
- Fukujuji Hospital Tokyo Japan
| | - Hideo Yasunaga
- Department of Clinical Epidemiology and Health Economics Graduate School of Medicine The University of TokyoTokyoJapan
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Pereira VB, da Cunha VP, Preisser TM, Souza BM, Turk MZ, De Castro CP, Azevedo MSP, Miyoshi A. Lactococcus lactis carrying a DNA vaccine coding for the ESAT-6 antigen increases IL-17 cytokine secretion and boosts the BCG vaccine immune response. J Appl Microbiol 2017; 122:1657-1662. [PMID: 28314076 DOI: 10.1111/jam.13449] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2017] [Revised: 03/08/2017] [Accepted: 03/14/2017] [Indexed: 12/19/2022]
Abstract
AIMS A regimen utilizing Bacille Calmette-Guerin (BCG) and another vaccine system as a booster may represent a promising strategy for the development of an efficient tuberculosis vaccine for adults. In a previous work, we confirmed the ability of Lactococcus lactis fibronectin-binding protein A (FnBPA+) (pValac:ESAT-6), a live mucosal DNA vaccine, to produce a specific immune response in mice after oral immunization. In this study, we examined the immunogenicity of this strain as a booster for the BCG vaccine in mice. METHODS AND RESULTS After immunization, cytokine and immunoglobulin profiles were measured. The BCG prime L. lactis FnBPA+ (pValac:ESAT-6) boost group was the most responsive group, with a significant increase in splenic pro-inflammatory cytokines IL-17, IFN-γ, IL-6 and TNF-α compared with the negative control. CONCLUSIONS Based on the results obtained here, we demonstrated that L. lactis FnBPA+ (pValac:ESAT-6) was able to increase the BCG vaccine general immune response. SIGNIFICANCE AND IMPACT OF THE STUDY This work is of great scientific and social importance because it represents the first step towards the development of a booster to the BCG vaccine using L. lactis as a DNA delivery system.
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Affiliation(s)
- V B Pereira
- Laboratório de Tecnologia Genética, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - V P da Cunha
- Laboratório de Tecnologia Genética, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - T M Preisser
- Laboratório de Tecnologia Genética, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - B M Souza
- Laboratório de Tecnologia Genética, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - M Z Turk
- Laboratório de Tecnologia Genética, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - C P De Castro
- Laboratório de Tecnologia Genética, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - M S P Azevedo
- Laboratório de Tecnologia Genética, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - A Miyoshi
- Laboratório de Tecnologia Genética, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
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Efficacy of Treatment for Latent Tuberculosis in Patients Undergoing Treatment with a Tumor Necrosis Factor Antagonist. Ann Am Thorac Soc 2017; 14:690-697. [DOI: 10.1513/annalsats.201608-647oc] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
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Cheon JH. Understanding the complications of anti-tumor necrosis factor therapy in East Asian patients with inflammatory bowel disease. J Gastroenterol Hepatol 2017; 32:769-777. [PMID: 27723166 DOI: 10.1111/jgh.13612] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/02/2016] [Indexed: 02/06/2023]
Abstract
Remarkable advances have been made in the treatment of inflammatory bowel disease since the introduction of anti-tumor necrosis factor-α agents, especially for patients who are refractory to or cannot tolerate conventional therapies. Currently, infliximab, adalimumab, and golimumab are available in the East Asian medical market, and these agents have been shown to be effective for inducing and maintaining long-term remission of inflammatory bowel disease. Despite their clinical benefits, anti-tumor necrosis factor therapy can also lead to increased vulnerability to infections, development of autoimmune diseases and malignancy, and decreased immunogenicity of vaccinations. Because infectious diseases, such as tuberculosis, hepatitis, and influenza, remain major health problems in East Asia, more cautious use of biologics is needed. To further improve treatment efficacy and safety, close monitoring of inflammation, regular surveillance for malignancy, and regularly scheduled vaccinations are needed. Treatment strategies for biologics should be customized to meet the needs of different patients.
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Affiliation(s)
- Jae Hee Cheon
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
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27
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Shifrin H, Mouhadeb O, Gluck N, Varol C, Weinstock M. Cholinergic Anti-Inflammatory Pathway Does Not Contribute to Prevention of Ulcerative Colitis by Novel Indoline Carbamates. J Neuroimmune Pharmacol 2017; 12:484-491. [PMID: 28271317 DOI: 10.1007/s11481-017-9735-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2016] [Accepted: 02/28/2017] [Indexed: 12/27/2022]
Abstract
Indoline carbamates, AN680 and AN917 decrease cytokines, TNF-α and IL-6 in peritoneal macrophages activated by lipopolysaccharide (LPS) and in mouse tissues after LPS injection. They prevent nuclear translocation of nuclear factor κB (NF-κB) and activator protein 1. Only AN917 inhibits cholinesterase (ChE) at relevant concentrations. ChE inhibitors decrease NF-κB by activating α7 nicotinic acetylcholine receptors (α7nAChR). The current study compared the effect of rivastigmine, a ChE inhibitor, AN680 and AN917 on ulcerative colitis induced in mice by ingestion of dextran sodium sulfate (4.5%) solution. Rivastigmine (1 mg/kg), AN680 (2.5-10 mg/kg) and AN917 (2-5 mg/kg) were injected subcutaneously once daily for 8 days. Disease severity was assessed by disease activity index (DAI), colonoscopy, colon length and body weight loss, colonic levels of TNF-α, IL-6, IL-1β and myeloid peroxidase (MPO) activity. AN680 (5 mg/kg) reduced DAI, colon shrinkage, weight loss, histopathological signs of colon damage, MPO activity, TNF-α, IL-1β and IL-6 levels without inhibiting ChE. AN917 (5 mg/kg) and rivastigmine (1 mg/kg) inhibited ChE in plasma and colon by 65%, reduced DAI, MPO activity and IL-6, but not TNF-α or IL-1β. AN917 did not prevent weight loss or colon shrinkage. Mecamylamine abolished the reduction of DAI, MPO activity and IL-6 by AN917 and rivastigmine, indicating they were mediated by α7nAChR. CONCLUSIONS AN680 is very effective in preventing DSS-induced UC in mice and may therefore have potential therapeutic application in humans. Addition of ChE inhibition and indirect activation of α7nAChR lessens the efficacy of AN917 in this model.
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Affiliation(s)
- Helena Shifrin
- Institute of Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Odelia Mouhadeb
- Research Centre for Digestive Tract and Liver Diseases, Tel Aviv-Sourasky Medical Centre and Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Nathan Gluck
- Research Centre for Digestive Tract and Liver Diseases, Tel Aviv-Sourasky Medical Centre and Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Chen Varol
- Research Centre for Digestive Tract and Liver Diseases, Tel Aviv-Sourasky Medical Centre and Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Marta Weinstock
- Institute of Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel.
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Tuberculosis Screening and Reactivation Among a National Cohort of Patients with Inflammatory Bowel Disease Treated with Tumor Necrosis Factor Alpha Antagonists. Inflamm Bowel Dis 2017; 23:254-260. [PMID: 27997433 DOI: 10.1097/mib.0000000000001003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Tumor necrosis factor antagonists (anti-TNFs) are effective in treating inflammatory bowel disease (IBD) but may cause reactivation of tuberculosis (TB). TB screening rates and related outcomes are not well described among patients with IBD. This study aims to evaluate the prevalence and determinants of TB screening before anti-TNF initiation and related outcomes among patients with IBD. METHODS We identified patients with IBD with filled prescriptions for anti-TNFs using the National Veterans Affairs administrative data sets. Determinants of TB screening were identified by univariate and multivariate analyses. Patients with TB reactivation were identified by ICD9 codes or prescriptions for isoniazid, and confirmed by chart review. RESULTS A total of 3357 patients with IBD were identified with filled anti-TNF prescriptions. Approximately 72% to 86% of patients received TB screening. In multivariate analyses, patients in rural areas were less likely to be screened for TB compared with those in urban areas (odds ratio 0.72, 95% confidence ratio 0.54-0.95). Patients who received care at academically affiliated facilities were more likely to have received screening for TB (odds ratio 1.49, 95% confidence ratio 1.31-1.95). In 7210 patient-years of follow-up on anti-TNF, TB reactivation was confirmed in 2 patients, both of whom had a history and treatment of latent TB before anti-TNF initiation. CONCLUSIONS TB screening before anti-TNF is estimated to be between 72% and 86%. Receipt of care at urban, academic-affiliated, high-volume IBD facilities is associated with higher rates of screening. Reactivation of TB in a highly screened cohort is estimated to be 2.8 per 10,000 patient-years.
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29
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Hong SN, Kim HJ, Kim KH, Han SJ, Ahn IM, Ahn HS. Risk of incident Mycobacterium tuberculosis infection in patients with inflammatory bowel disease: a nationwide population-based study in South Korea. Aliment Pharmacol Ther 2017; 45:253-263. [PMID: 27933686 DOI: 10.1111/apt.13851] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2016] [Revised: 06/01/2016] [Accepted: 10/11/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND The low incidence of Mycobacterium tuberculosis infection and lack of adequate controls have prevented researchers from estimating tuberculosis (TB) risk in inflammatory bowel disease (IBD) patients. AIM To evaluate the risk of incident TB among IBD patients. METHODS Using the 2011-2013 data of the South Korean National Health Insurance (NHI) system, we calculated the incidence rates (IRs), standardised incidence ratio (SIR) and number needed to screen (NNS) for incident TB in IBD patients compared to the general population in terms of subtype, age, gender and IBD medications. RESULTS The IR, SIR and NNS for TB in IBD patients were 223.9/100 000 person-years, 2.64 (2.30-3.01) and 446.6 (392.8-517.6), respectively. The TB IR in Crohn's disease (CD) patients was significantly higher than that in ulcerative colitis (UC) patients (340.1/100 000 person-years vs. 165.5/100 000 person-years, respectively; P < 0.001). The SIR and NNS for TB among CD patients were 4.00 (3.59-4.45) and 604.2 (506.1-749.6), respectively; those among UC patients were 1.95 (1.66-2.27) and 294.0 (246.9-363.4). The TB IRs in IBD patients did not differ significantly by age or gender (Ptrend = 0.505 and P = 0.861, respectively). The TB IRs among IBD patients prescribed 5-ASA, corticosteroids, immunomodulators and anti-TNF-α were 143.5, 208.5, 284.6 and 554.1 per 100 000 person-years, respectively. Among IBD patients treated using anti-TNF-α, the TB IR was significantly higher than that among all IBD patients (P < 0.001); the SIR and NNS for TB were 6.53 (5.99-7.09) and 180.5 (144.6-240.1) respectively. CONCLUSION Clinicians should be aware of the increased risk of active tuberculosis in patients with IBD who are receiving anti-TNF-α therapy.
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Affiliation(s)
- S N Hong
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - H J Kim
- Department of Preventive Medicine, College of Medicine, Korea University, Seoul, South Korea
| | - K H Kim
- Department of Public Health, Graduate School, Korea University, Seoul, South Korea
| | - S-J Han
- Department of Public Health, Graduate School, Korea University, Seoul, South Korea
| | - I M Ahn
- Department of Preventive Medicine, College of Medicine, Korea University, Seoul, South Korea
| | - H S Ahn
- Department of Preventive Medicine, College of Medicine, Korea University, Seoul, South Korea
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Ko MKL, Ng SC, Mak LY, Li MK, Lo FH, Ng CKM, Lao WC, Tsang S, Chan KH, Hui YT, Shan EHS, Loo CK, Hui AJ, To WP, Hung IF, Leung WK. Infection-related hospitalizations in the first year after inflammatory bowel disease diagnosis. J Dig Dis 2016; 17:610-617. [PMID: 27533786 DOI: 10.1111/1751-2980.12397] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Revised: 08/09/2016] [Accepted: 08/14/2016] [Indexed: 12/11/2022]
Abstract
OBJECTIVE With the rapid increase in the incidence of inflammatory bowel disease (IBD) in Asia, the natural course of the early phase of disease in these patients remains poorly defined. This study aimed to determined the incidence and characteristics of infection-related hospitalization in the first year in patients newly diagnosed with IBD in Hong Kong SAR, China. METHODS Patients newly diagnosed with IBD and enrolled in the territory-wide Hong Kong IBD Registry were identified. Details of their hospitalization within the first 12 months after diagnosis were retrieved and analyzed. RESULTS Altogether 433 newly diagnosed IBD patients were enrolled, including 188 with Crohn's disease (CD), 230 with ulcerative colitis (UC) and 15 with IBD-unclassified (IBD-U). Among them, 110 (25.4%) had at least one unscheduled hospitalization in the first year and 34 (7.9%) had infection-related hospitalization, leading to 43 (23.4%) of total hospitalizations. Gastrointestinal tract (30.2%), respiratory tract (34.9%) and skin and soft tissues (11.6%) were the most common sites of infection. Bacterial and viral infections accounted for 46.7% and 20.8% of hospitalizations for infection, respectively. Common identified pathogens included Clostridium difficile (16.3%) and Cytomegalovirus (11.6%). Multivariate analysis found that patient's age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.06) and the presence of comorbidity (OR 2.32, 95% CI 1.05-5.13) were significantly associated with hospitalization from infection in IBD patients. CONCLUSIONS Infection-related hospitalizations were found in 7.9% of newly diagnosed IBD patients within the first year after diagnosis in Hong Kong, which accounted for about one-quarter of all unscheduled hospitalizations. Elder patients with concurrent illnesses were at higher risk.
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Affiliation(s)
| | - Siew C Ng
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Lung-Yi Mak
- Department of Medicine, University of Hong Kong, Hong Kong SAR, China
| | - Michael K Li
- Department of Medicine and Geriatrics, Tuen Mun Hospital, Kowloon, Hong Kong SAR, China
| | - Fu Hang Lo
- Department of Medicine and Geriatrics, United Christian Hospital, Kowloon, Hong Kong SAR, China
| | - Carmen Ka Man Ng
- Department of Medicine and Geriatrics, Princess Margaret Hospital, Kowloon, Hong Kong SAR, China
| | - Wai Cheung Lao
- Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong SAR, China
| | - Steve Tsang
- Department of Medicine, Tseung Kwan O Hospital, Hong Kong SAR, China
| | - Kam Hon Chan
- Department of Medicine, North District Hospital, New Territorities, Hong Kong SAR, China
| | - Yee Tak Hui
- Department of Medicine, Queen Elizabeth Hospital, Kowloon, Hong Kong SAR, China
| | - Edwin Hok Shing Shan
- Department of Medicine and Geriatrics, Caritas Medical Centre, Kowloon, Hong Kong SAR, China
| | - Ching Kong Loo
- Department of Medicine and Geriatrics, Kwong Wah Hospital, Kowloon, Hong Kong SAR, China
| | - Aric J Hui
- Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, New Territorities, Hong Kong SAR, China
| | - Wai Pan To
- Department of Medicine, University of Hong Kong, Hong Kong SAR, China
| | - Ivan F Hung
- Department of Medicine, University of Hong Kong, Hong Kong SAR, China
| | - Wai K Leung
- Department of Medicine, University of Hong Kong, Hong Kong SAR, China
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Lee JW, Choi CH, Park JH, Kim JW, Kang SB, Koo JS, Kim YH, Kim YS, Joo YE, Chang SK. Clinical features of active tuberculosis that developed during anti-tumor necrosis factor therapy in patients with inflammatory bowel disease. Intest Res 2016; 14:146-51. [PMID: 27175115 PMCID: PMC4863048 DOI: 10.5217/ir.2016.14.2.146] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2015] [Revised: 03/20/2016] [Accepted: 03/21/2016] [Indexed: 12/27/2022] Open
Abstract
Background/Aims Anti-tumor necrosis factor (TNF) therapy for active ulcerative colitis (UC) and Crohn's disease (CD) is associated with increased risks of tuberculosis (TB) infection. We analyzed the incidence and clinical features of Korean patients with inflammatory bowel disease (IBD) who developed active TB during anti-TNF therapy. Methods Ten cases of active TB developed in patients treated with infliximab (n=592) or adalimumab (n=229) for UC (n=160) or CD (n=661) were reviewed. We analyzed demographics, interval between start of anti-TNF therapy and active TB development, tests for latent TB infection (LTBI), concomitant medications, and the details of diagnosis and treatments for TB. Results The incidence of active TB was 1.2% (10/821): 1.5% (9/592) and 0.4% (1/229) in patients receiving infliximab and adalimumab, respectively. The median time to the development of active TB after initiation of anti-TNF therapy was three months (range: 2–36). Three patients had past histories of treatment for TB. Positive findings in a TB skin test (TST) and/or interferon gamma releasing assay (IGRA) were observed in three patients, and two of them received anti-TB prophylaxis. Two patients were negative by both TST and IGRA. The most common site of active TB was the lungs, and the active TB was cured in all patients. Conclusions Active TB can develop during anti-TNF therapy in IBD patients without LTBI, and even in those with histories of TB treatment or LTBI prophylaxis. Physicians should be aware of the potential for TB development during anti-TNF therapy, especially in countries with a high prevalence of TB.
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Affiliation(s)
- Jang Wook Lee
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Chang Hwan Choi
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Ji Hoon Park
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Jeong Wook Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Sang Bum Kang
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Daejeon, Korea
| | - Ja Seol Koo
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Young-Ho Kim
- Department of Internal Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - You Sun Kim
- Department of Internal Medicine, Inje University College of Medicine, Seoul, Korea
| | - Young Eun Joo
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Sae Kyung Chang
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
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Yi YX, Han JB, Zhao L, Fang Y, Zhang YF, Zhou GY. Tumor necrosis factor alpha gene polymorphism contributes to pulmonary tuberculosis susceptibility: evidence from a meta-analysis. Int J Clin Exp Med 2015; 8:20690-20700. [PMID: 26884992 PMCID: PMC4723837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2015] [Accepted: 11/02/2015] [Indexed: 06/05/2023]
Abstract
This study is to estimate the association between polymorphisms in the tumor necrosis factor alpha (TNF-α) gene and pulmonary tuberculosis susceptibility (pTB). Studies were identified by searching PubMed and ISI web of Knowledge. The strength of association between the TNF-α gene and pTB susceptibility was assessed by odds ratios. Totals of 18 studies including 2, 735 cases and 3, 177 controls were identified referring to four single-nucleotide polymorphisms: -308G>A, -863C>A, -857C>T and -238G>A. The significantly associations were found between -308G>A (Dominant model: OR 0.53, 95% CI 0.35-0.81, P=0.004; Homozygote model: OR 0.51, 95% CI 0.33-0.78, P=0.002), -238G>A (Dominant model: OR 0.33, 95% CI 0.18-0.57, P<0.001) and pTB susceptibility. The results showed that the variant genotype of TNF-α -308G>A was protective in pooled groups of patients with pTB in the dominant genetic model (OR 0.16, 95% CI 0.06-0.39, P<0.001), the homozygote comparison (OR 0.14, 95% CI 0.06-0.36, P<0.001) in African, while that was with -238G>A in the dominant genetic model (OR 0.31, 95% CI 0.18-0.56, P<0.001) in Asian. Our meta-analysis suggest TNF-α -308G>A and -238G>A polymorphisms increases the risk of pTB susceptibility regardless of ethnicity and HIV statue. In Asian population, the significantly association with pTB is TNF-α -238G>A, while TNF-α -308G>A is in African population.
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Affiliation(s)
- Yong-Xiang Yi
- Department of Hepatobiliary Surgery, The Second Hospital of Nanjing, Affiliated to Southeast UniversityNanjing 210003, China
| | - Jian-Bo Han
- Department of Hepatobiliary Surgery, The Second Hospital of Nanjing, Affiliated to Southeast UniversityNanjing 210003, China
| | - Liang Zhao
- Department of Hepatobiliary Surgery, The Second Hospital of Nanjing, Affiliated to Southeast UniversityNanjing 210003, China
| | - Yuan Fang
- Department of Immunotherapy, The Second Hospital of Nanjing, Affiliated to Southeast UniversityNanjing 210003, China
| | - Yu-Feng Zhang
- Department of Hepatobiliary Surgery, The Second Hospital of Nanjing, Affiliated to Southeast UniversityNanjing 210003, China
| | - Guang-Yao Zhou
- Department of Infectious Disease, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhou 325027, China
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