175studies have shown immunologic response to vaccines while on immunosuppres-
sive medications, including anti-TNF therapy, although the response may be
attenuated when on anti-TNF therapy alone or in combination therapy with an
immunomodulator. In one prospective cohort of 60 children with IBD and 53
healthy controls receiving influenza vaccine, the proportion of patient who
achieve serologic protection to influenza A was similar to controls, regardless of
whether treated with immunosuppressive therapy [ 59 ]. However, the response to
influenza B was decreased in the IBD population, and immunosuppression did
impact response, but 55% still had immunogenicity. Mamula et al. reported com-
parable findings in 51 pediatric IBD patients and 29 healthy controls; patients on
combination therapy with infliximab and immunomodulatory therapy were less
likely to respond to influenza A and B antigens, with serologic conversion rates
ranging from 90% for influenza A (H3) to 38% for influenza B [ 60 ]. Patients on
anti-TNF alone were not evaluated, and therefore, it is unclear if the response
would be different in this subgroup. Lu et al. reported a similar level of seropro-
tection in children and young adults with IBD against influenza A (H1N1, H3N2)
and B in immunosuppressed compared to nonimmunosuppressed patients,
including those patients receiving anti-TNF therapy. Influenza vaccine timing in
relation to infusion (at the time of infusion versus midway between infusions)
does not appear to affect immunologic response [ 61 ]. With regard to other inac-
tivated vaccines, there has been one study of hepatitis B vaccine status and
response of 100 pediatric IBD patients receiving infliximab [ 62 ]. Forty- four per-
cent of previously vaccinated children were not immune to hepatitis B at initia-
tion of therapy; of the 36 children who received a booster vaccination, 76% had
an anamnestic response indicating adequate immunity postvaccination, but chil-
dren who received infliximab at more frequent intervals were less likely to
respond. There is no specific pediatric data, but adult studies have shown a
decreased response to pneumococcal and tetanus/pertussis vaccination in IBD
patients receiving anti-TNF therapy alone or in combination therapy compared to
IBD patients not on immunosuppressive therapy and healthy controls, with the
combination therapy leading to significantly decreased immunogenicity to teta-
nus and pertussis; however, some patients do still have an appropriate response
[ 63 , 64 ]. Based on these combined results, if possible, pediatric IBD patients
should receive this vaccination prior to initiating any immunosuppressants; how-
ever, in the real world, this is not always feasible given the severity of disease. In
the studies that specifically evaluated safety, inactivated vaccines were generally
well tolerated, and therefore, despite the concern of decreased immunogenicity,
for patients receiving anti-TNF therapy, the benefits of vaccination outweigh the
risk. Clinicians need to monitor these patients closely and have a low index of
suspicion for evaluating for these infections and initiating appropriate treatment
when available regardless of vaccination status. Despite the recommendation for
vaccinating patients with IBD, there remains practice variation in the assessment
of immunization status in patients with pediatric IBD. In a survey of 178 pediat-
ric gastroenterologists participating in the ImproveCareNow quality improve-
ment network, only 51% of respondents inquired about immunization status, and
11 Biologic Therapy in Pediatric Inflammatory Bowel Disease