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In general, patients who develop severe infusion or injection reactions are rec-
ommended to change therapy to another agent [ 18 ]. The decision to rechallenge is
largely based on the severity of hypersensitivity reactions and potential clinical ben-
efit of further treatment. If no alternatives are available, Lichtenstein and colleagues
proposed pretreatment with antihistamine and corticosteroid (prednisone 50 mg
every 8 h for 24 h prior to the infusion) or desensitization using graded administra-
tion of the offending drug escalating to the target dose that is clinically tolerated
[ 18 ]. The sequential exposure to low-dose antigen could desensitize mast cells and
basophils to the offending drug [ 18 ]. Data on desensitization to infliximab is limited
to case reports and case series with breakthrough reaction rates of up to 29% similar
to the rate observed in those without desensitization, though breakthrough reactions
are generally milder allowing for the continuation of therapy [ 18 ].
Primary prophylaxis may be necessary in certain selected patient populations,
particularly those who have had prolonged drug-free intervals [ 3 , 11 , 22 ]. In a ret-
rospective single-center study, infliximab trough and anti-drug antibody levels were
collected from 128 IBD patients that reinitiated infliximab therapy after a median of
15 months (range 6–125 months) [ 8 ]. At the time when infliximab was restarted,
none of the patients in this study had a detectable ATI [ 8 ]. After reexposure to inf-
liximab, ATIs were detected in 40% at week 2 [ 8 ]. Ben-Horin et al. also demon-
strated that ATI declines to undetectable levels within 1 year after cessation of
infliximab therapy in the majority of patients (13/16, 81.3%) [ 23 ]. Therefore, in
patients who have had a drug-free interval of 12 months or greater, assessment of
anti-drug antibodies will not be helpful before reinitiating therapy; however, ATI
can be assessed before the next infusion to help predict which patients will develop
acute infusion reactions.
Strategies for primary prophylaxis are similar to secondary prophylaxis as
described, which include gradual increase of infusion rate, co-administration of an
immunomodulator, and premedication with acetaminophen, diphenhydramine, and
steroid [ 18 , 19 ]. Premedication with intravenous hydrocortisone can reduce ATI
[ 24 ]. In a randomized placebo-controlled trial consisting of 53 Crohn’s disease
(CD) patients receiving infliximab, only 26% of hydrocortisone-treated patients
developed ATI compared with 42% of placebo-treated patients (p = 0.06) [ 24 ].
Additionally, ATI levels were lower at week 16 among patients treated with hydro-
cortisone (1.6 vs. 3.4 μg/mL, p = 0.02) [ 24 ]. Patients treated with adalimumab
should first allow the drug to reach room temperature and ice the injection site
before administering the injection.
Psoriasiform and Eczematiform Lesions
Clinical Presentation
Development of psoriasiform or eczematiform lesions has been reported in patients
treated with anti-TNF therapy [ 25 – 28 ]. Although anti-TNF therapy is used to treat
psoriasis, IBD patients can paradoxically develop these immune-mediated
U. Wong and R.K. Cross