Adverse events associated with common therapy regimens for moderate-to-severe Crohn's disease.
OBJECTIVE
We sought to determine whether treatment with steroids, immunosuppressives (ISs), and anti-tumor necrosis factor (TNF) agents is associated with an increased risk of adverse events in patients with Crohn's disease (CD).


METHODS
This study analyzed claims from patients with CD and controls without CD from the United States with private insurance (2002-2005). Patients were classified by treatment with steroids, ISs, anti-TNF agents, combinations of two or three, and none of these medications. Follow-up adverse events in patients with CD and controls were compared across different treatment categories and are presented as hazard ratios (HRs) and 95% confidence intervals (CIs). Within the CD patients, a subset analysis examined the relationship between therapies and outcomes.


RESULTS
A total of 22,310 patients with CD (8,581 longitudinal cohort cases) and 111,550 controls were identified. Compared with the controls, CD patients had higher rate ratios for all pre-specified events. Within the CD patient population subgroup, monotherapy with steroids, ISs, or anti-TNF agents was associated with an increased risk of tuberculosis (TB) (HR 2.7; 95% CI, 1.0-7.3), candidiasis (HR 2.7; 95% CI, 1.8-4.0), herpes zoster (HR 1.7; 95% CI, 1.0-2.7), sepsis (HR 1.3; 95% CI, 1.1-1.5), demyelinating conditions (HR 3.2; 95% CI, 1.5-6.9), and cervical dysplasia (HR 1.5; 95% CI, 1.2-2.0) as compared with patients not receiving these medications. The use of two or three of these medications further increased these risks: TB (HR 7.4; 95% CI, 2.1-26.3), candidiasis (HR 3.8; 95% CI, 2.0-7.6), herpes zoster (HR 3.7; 95% CI, 1.8-7.5), sepsis (HR 1.6; 95% CI, 1.2-2.1), and cervical dysplasia (HR 1.8; 95% CI, 1.1-3.0).


CONCLUSIONS
Treatment with steroids, ISs, or anti-TNF agents singly and in combination in patients with CD is associated with increased risks of infection, demyelinating disorders, and cervical dysplasia.
Marehbian
Josh
J
Health Benchmarks, Woodland Hills, California, USA.
Arrighi
H Michael
HM
Hass
Steve
S
Tian
Haijun
H
Sandborn
William J
WJ
D000068879:Adalimumab; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use; D019819:Budesonide / Q000009:adverse effects / Q000627:therapeutic use; D016022:Case-Control Studies; D015897:Comorbidity; D003424:Crohn Disease / Q000188:drug therapy* / Q000453:epidemiology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000069285:Infliximab; D008137:Longitudinal Studies; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects / Q000627:therapeutic use; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D015995:Prevalence; D016016:Proportional Hazards Models; D013256:Steroids / Q000009:adverse effects* / Q000627:therapeutic use; D014481:United States / Q000453:epidemiology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D013256:Steroids; D019819:Budesonide; D000069285:Infliximab; D015122:Mercaptopurine; D000068879:Adalimumab; D001379:Azathioprine; D011241:Prednisone; D008727:Methotrexate