title: Different Risk of Tuberculosis and Efficacy of Isoniazid Prophylaxis in Rheumatoid Arthritis Patients with Biologic Therapy: A Nationwide Retrospective Cohort Study in Taiwan.
abstract: Increasing evidence indicates an increased risk of tuberculosis (TB) for rheumatoid arthritis (RA) patients receiving biologic therapy, and the effectiveness of isoniazid prophylaxis (INHP) in TB prevention. We aimed to examine 1) the incidence rate (IR) and risk factors for TB among RA patients receiving different therapies; 2) INHP effectiveness for TB prevention; 3) mortality rates after TB diagnosis in patients receiving different therapies. This retrospective study was conducted using a nationwide database: 168,720 non-RA subjects and a total of 42,180 RA patients including 36,162 csDMARDs-exposed, 3,577 etanercept-exposed, 1,678 adalimumab-exposed and 763 rituximab-exposed patients. TB risk was 2.7-fold higher in RA cohort compared with non-RA group, with an adjusted hazard ratio (aHR) of 2.58. Advanced age, male, the use of corticosteroids ≧ 5 mg/day, and the presence of diabetes mellitus (DM), chronic obstructive pulmonary disease and chronic kidney disease were risk factors for developing TB. Using csDMARDs-exposed group as reference, aHR of TB was the highest with adalimumab treatment (1.52), followed by etanercept (1.16), and the lowest with rituximab (0.08). INHP could effectively reduce TB risk in biologics-exposed patients. Mortality rates after TB diagnosis were higher in RA patients, particularly the elderly and those with DM, with lower rates in adalimumab-exposed patients compared with csDMARDs-exposed patients. In conclusion, TB risk was increased in patients receiving TNF-α inhibitors, but the risk associated with rituximab therapy was relatively low. With the effectiveness of INHP shown in the prevention of biologics-associated TB, stricter implementation of INHP should be beneficial. The mortality from biologics-associated TB may be efficiently reduced through increased awareness.
authors.affiliation: Department of Medical Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan.|Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Tsai-Ling
authors.initials: TL
authors.lastname: Liao
authors.affiliation: Department of Medical Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan.|Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan.
authors.forename: Ching-Heng
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Department of Medical Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan.|Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.|Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital and Faculty of Medicine, National Yang Ming University, Taipei, Taiwan.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Chen
authors.affiliation: Department of Medical Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Chia-Li
authors.initials: CL
authors.lastname: Chang
authors.affiliation: Department of Medical Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan.|Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital and Faculty of Medicine, National Yang Ming University, Taipei, Taiwan.
authors.forename: Hsin-Hua
authors.initials: HH
authors.lastname: Chen
authors.affiliation: Department of Medical Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan.|Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.|Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital and Faculty of Medicine, National Yang Ming University, Taipei, Taiwan.|Institute of Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Der-Yuan
authors.initials: DY
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000401:mortality; D001691:Biological Therapy / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015994:Incidence; D007538:Isoniazid / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000502:physiology; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D013624:Taiwan / Q000453:epidemiology; D014376:Tuberculosis / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D007538:Isoniazid