176
30.9% obtained records at the time of diagnosis, a time where there may be
opportunities and strategies available for catch-up vaccination prior to initiation
of high-dose immunosuppression [ 65 ].
Anti-TNF Therapy and Malignancy in Pediatric IBD
Side effects and risks of therapy, including hypersensitivity reactions, infectious
complications, and psoriasis, are similar in pediatric patients and are discussed
extensively elsewhere in this publication; however, special consideration should
be given to the risk of malignancy as this is often the risk that leads to hesitation
and indecision for parents and caretakers. Although malignancies, specifically
lymphomas, have been reported with anti-TNF agents, there is a growing evidence
that the increased risk may be due to combination therapy with thiopurines rather
than anti- TNF therapy alone. The most concerning malignancy is hepatosplenic
T-cell lymphoma (HSTCL), which has an aggressive course and is often refractory
to standard chemotherapy and stem cell transplant. Several cases were reported in
the pediatric literature from 2003 to 2006, and by October 2006, there were eight
cases of HSTCL in adolescent and young adults treated with anti-TNF reported to
the Food and Drug Administration Adverse Event Reporting System [ 66 ]. Initial
reports were in patients treated with infliximab, but with time and increased use,
additional cases were observed after treatment with adalimumab. A systematic
review of 36 IBD patients with HSTCL by Kotlyar et al. investigated clinical fac-
tors that may impact risk [ 67 ]. All 36 patients who developed HSTCL had received
thiopurines, and 20 patients (56%) had received concomitant anti-TNF therapy.
Risk factors identified included young age (age 10–35 years), male sex (86% of
cases where gender was known), and long-term treatment (>2 years) with thiopu-
rines. Although there may be some reporting bias, no cases of HSTCL have been
reported in IBD patients treated with anti-TNF monotherapy; however, HTSCL
has been reported in one patient with rheumatoid arthritis while receiving anti-
TNF therapy without concomitant thiopurines [ 68 ]. A more recent systematic
review evaluated the risk of lymphoma with anti-TNF for pediatric IBD [ 69 ].
Rates of lymphoma of pediatric patients treated with anti-TNF were compared to
nonexposed pediatric subjects and adult IBD patients exposed to anti-TNF agents.
Two patients treated with anti-TNF therapy developed lymphoma (absolute risk
2.1/10,000 patient-years of follow-up evaluation), which was comparable to the
expected rate of lymphoma in the general pediatric population. Although not sta-
tistically significant, the rate of lymphoma was lower than the rate in pediatric IBD
patients treated with thiopurines and adult IBD patients treated with anti-TNF
therapy. Finally, a recent analysis of the DEVELOP registry, a prospective long-
term registry of pediatric IBD patients (5766 patients; 24,543 patient-years of
follow-up), found no increased risk of malignancy or hemophagocytic lymphohis-
tiocytosis (HLH) in patients exposed to infliximab compared to those unexposed
to biologics [ 70 ]. However, a trend toward an increased risk of malignancy was
S. Patel and J. Strople