Crohn's Disease Activity and Concomitant Immunosuppressants Affect the Risk of Serious and Opportunistic Infections in Patients Treated With Adalimumab.

OBJECTIVES: 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.

METHODS: 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).

RESULTS: 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.

CONCLUSIONS: 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.