Crohn's Disease Activity and Concomitant Immunosuppressants Affect the Risk of Serious and Opportunistic Infections in Patients Treated With Adalimumab.
Anti-tumor necrosis factor (TNF) drugs are commonly used to treat moderate-to-severe Crohn's disease (CD). Both the activity of CD and the concomitant immunosuppressants (corticosteroids and immunomodulators) used with anti-TNF drugs could increase the risk of infection. We determined the relative risk of serious and opportunistic infections associated with increasing disease activity and concomitant immunomodulators and corticosteroids in patients with CD treated with adalimumab.



This pooled analysis identified incident treatment-emergent serious and opportunistic infections among patients with CD in clinical trials of adalimumab. Disease activity was assessed with the Crohn's Disease Activity Index (CDAI).



The analysis included 2,266 patients treated with adalimumab with median age 35 years. Higher disease activity was associated with significantly increased risks of both serious and opportunistic infections at 1 year, with each 100-point increase in CDAI associated with a >30% increased risk of each type of infection. Concomitant use of immunomodulators was associated with a significant >3-fold decreased risk of serious infection (hazard ratio (HR) 0.29 (0.08-0.98), P=0.045) by 1 year. Concomitant use of corticosteroids was associated with a significantly increased risk of serious infection by day 120 (HR 2.40 (1.33-4.35), P=0.004). Concomitant use of either category of immmunosuppressant was associated with numerically higher rates of opportunistic infection, 40% of which were due to herpes zoster, compared with adalimumab monotherapy.



Higher disease activity in CD is associated with significantly increased risks of both serious and opportunistic infections. In addition to corticosteroid-sparing strategies, consideration should be given to expanding herpes zoster vaccination guidelines to include younger patients.
University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Mark T
MT
Osterman
Division of Gastroenterology, University of California San Diego, La Jolla, California, USA.
William J
WJ
Sandborn
Mount Sinai Medical Center, New York, USA.
Jean-Frederic
JF
Colombel
Inserm U954 and Department of Gastroenterology, Nancy University Hospital, Université de Lorraine, Vandoeuvre-les-Nancy, France.
Laurent
L
Peyrin-Biroulet
AbbVie Inc., North Chicago, Illinois, USA.
Anne M
AM
Robinson
AbbVie Inc., North Chicago, Illinois, USA.
Qian
Q
Zhou
University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
James D
JD
Lewis
D000068879:Adalimumab / Q000627:therapeutic use*; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003424:Crohn Disease / Q000188:drug therapy* / Q000503:physiopathology; D004359:Drug Therapy, Combination; D005260:Female; D006562:Herpes Zoster / Q000453:epidemiology*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D015999:Multivariate Analysis; D009894:Opportunistic Infections / Q000453:epidemiology*; D016016:Proportional Hazards Models; D012307:Risk Factors; D012720:Severity of Illness Index; D055815:Young Adult
D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D000068879:Adalimumab; D008727:Methotrexate
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