One-Year Tuberculosis Risk in Rheumatoid Arthritis Patients Starting Their First Tumor Necrosis Factor Inhibitor Therapy from 2008 to 2012 in Taiwan: A Nationwide Population-Based Cohort Study.
OBJECTIVE
To investigate the risk of tuberculosis (TB) among rheumatoid arthritis (RA) patients within 1 year after initiation of tumor necrosis factor inhibitor (TNFi) therapy from 2008 to 2012.


METHODS
We used the 2003-2013 Taiwanese National Health Insurance Research Database to identify RA patients who started any RA-related medical therapy from 2008 to 2012. Those who initiated etanercept or adalimumab therapy during 2008-2012 were selected as the TNFi group and those who never received biologic disease-modifying anti-rheumatic drug therapy were identified as the comparison group after excluding the patients who had a history of TB or human immunodeficiency virus infection/acquired immune deficiency syndrome. We used propensity score matching (1:6) for age, sex, and the year of the drug index date to re-select the TNFi group and the non-TNFi controls. After adjusting for potential confounders, hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to examine the 1-year TB risk in the TNFi group compared with the non-TNFi controls. Subgroup analyses according to the year of treatment initiation and specific TNFi therapy were conducted to assess the trend of 1-year TB risk in TNFi users from 2008 to 2012.


RESULTS
This study identified 5,349 TNFi-treated RA patients and 32,064 matched non-TNFi-treated controls. The 1-year incidence rates of TB were 1,513 per 105 years among the TNFi group and 235 per 105 years among the non-TNFi controls (incidence rate ratio, 6.44; 95% CI, 4.69-8.33). After adjusting for age, gender, disease duration, comoridities, history of TB, and concomitant medications, TNFi users had an increased 1-year TB risk (HR, 7.19; 95% CI, 4.18-12.34) compared with the non-TNFi-treated controls. The 1-year TB risk in TNFi users increased from 2008 to 2011 and deceased in 2012 when the Food and Drug Administration in Taiwan announced the Risk Management Plan for patients scheduled to receive TNFi therapy.


CONCLUSIONS
This study showed that the 1-year TB risk in RA patients starting TNFi therapy was significantly higher than that in non-TNFi controls in Taiwan from 2008 to 2012.
Rheumatology Unit, Department of Internal Medicine, Pulau Pinang General Hospital, Georgetown, Malaysia.|Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
Chong-Hong
CH
Lim
Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
Ching-Heng
CH
Lin
Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, Chung-Hsing University, Taichung, Taiwan.|School of Medicine, Chung-Shan Medical University, Taichung, Taiwan.|Department of Medical Education, Taichung Veterans General Hospital, Taichung, Taiwan.
Der-Yuan
DY
Chen
Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.|Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, Chung-Hsing University, Taichung, Taiwan.
Yi-Ming
YM
Chen
Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.|Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
Wen-Cheng
WC
Chao
Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.|Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, Chung-Hsing University, Taichung, Taiwan.
Tsai-Ling
TL
Liao
Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.|Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, Chung-Hsing University, Taichung, Taiwan.|School of Medicine, Chung-Shan Medical University, Taichung, Taiwan.|Institute of Public Health and Community Medicine Research Center, National Yang-Ming University, Taipei, Taiwan.
Hsin-Hua
http://orcid.org/0000-0002-7304-4587
HH
Chen
D000068879:Adalimumab / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000188:drug therapy*; D015331:Cohort Studies; D000068800:Etanercept / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D014376:Tuberculosis / Q000175:diagnosis / Q000209:etiology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab; D000068800:Etanercept