Increased risk of mycobacterial infections associated with anti-rheumatic medications.
BACKGROUND
Anti-tumour necrosis factor (TNF) agents and other anti-rheumatic medications increase the risk of TB in rheumatoid arthritis (RA). Whether they increase the risk of infections with nontuberculous mycobacteria (NTM) is uncertain.


OBJECTIVE
To determine the effect of anti-TNF therapy and other anti-rheumatic drugs on the risk of NTM disease and TB in older patients with RA.


METHODS
Population-based nested case-control study among Ontario seniors aged ≥67 years with RA who were prescribed at least one anti-rheumatic medication between 2001 and 2011. We identified cases of TB and NTM disease microbiologically and identified drug exposures using linked prescription drug claims. We estimated ORs using conditional logistic regression, controlling for several potential confounders.


RESULTS
Among 56 269 older adults with RA, we identified 37 cases of TB and 211 cases of NTM disease; each case was matched to up to 10 controls. Individuals with TB or NTM disease were both more likely to be using anti-TNF therapy (compared with non-use); adjusted ORs (95% CIs) were 5.04 (1.27 to 20.0) and 2.19 (1.10 to 4.37), respectively. Exposure to leflunomide and other anti-rheumatic drugs with high immunosuppressing potential also were associated with both TB and NTM disease, while oral corticosteroids and hydroxychloroquine were associated with NTM disease.


CONCLUSIONS
Anti-TNF use is associated with increased risk of both TB and NTM disease, but appears to be a relatively greater risk for TB. Several other anti-rheumatic drugs were also associated with mycobacterial infections.
Joint Division of Respirology, Department of Medicine, University Health Network and Mount Sinai Hospital, Toronto, Ontario, Canada West Park Healthcare Centre, Toronto, Ontario, Canada Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Sarah K
SK
Brode
Public Health Ontario, Toronto, Ontario, Canada Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Frances B
FB
Jamieson
Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.
Ryan
R
Ng
Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.
Michael A
MA
Campitelli
Public Health Ontario, Toronto, Ontario, Canada Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada Toronto Western Family Health Team, University Health Network, Toronto, Ontario, Canada.
Jeffrey C
JC
Kwong
Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada Department of Family Medicine, McMaster University, Hamilton, Ontario, Canada.
J Michael
JM
Paterson
Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.
Ping
P
Li
Public Health Ontario, Toronto, Ontario, Canada.
Alex
A
Marchand-Austin
Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada Toronto General Hospital Research Institute, Toronto, Ontario, Canada.
Claire
C
Bombardier
Joint Division of Respirology, Department of Medicine, University Health Network and Mount Sinai Hospital, Toronto, Ontario, Canada Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Theodore K
TK
Marras
D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology; D016022:Case-Control Studies; D016208:Databases, Factual; D004363:Drug Utilization / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D009165:Mycobacterium Infections, Nontuberculous / Q000139:chemically induced* / Q000150:complications / Q000453:epidemiology; D009864:Ontario / Q000453:epidemiology; D009894:Opportunistic Infections / Q000139:chemically induced* / Q000150:complications / Q000453:epidemiology; D018570:Risk Assessment / Q000379:methods; D014376:Tuberculosis / Q000139:chemically induced* / Q000150:complications / Q000453:epidemiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D018501:Antirheumatic Agents; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha
Respiratory Infection; Rheumatoid lung disease; Tuberculosis