Danese et al evaluated patients with Crohn's disease who are no longer responding to anti-TNF-alpha therapy. The authors are form the IRCCS Istituto Clinico Humanitas Rozzano in Milan.


Factors that contribute to a loss of response to anti-TNF-alpha therapy:

(1) antibodies to anti-TNF-alpha

(2) autoantibodies (ANA, anti-DNA)

(3) drug interactions that increase metabolism and clearance

(4) augmented clearance from other causes

(5) high baseline WBC count


In addition, compliance may be an issue because of the cost of the therapy.


Options for managing a patient who is no longer responding to anti-TNF-alpha:

(1) make sure that the person is actually getting the anti-TNF-alpha therapy

(2) adjustment in other drugs that may be interfering with anti-TNF-alpha therapy

(3) correction of factors associated with enhanced drug clearance if possible

(4) increase dose (dose escalation) and/or increase dose frequency (reduced infusion interval)

(5) if the above steps fail then it may be necessary to switch to an alternative biologic agent


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