Immunotherapy Safety for the Primary Care ... - U.S. Coast Guard

J ALLERGY CLIN IMMUNOL
VOLUME 120, NUMBER 3
Cox et al S43
Measures of efficacy
Summary Statement 12: Clinical parameters, such as
symptoms and medication use, might be useful measures
of the efficacy of immunotherapy in a clinical setting;
however, repetitive skin testing of patients receiving
immunotherapy is not recommended. A
Whether immunotherapy is effective can be determined
by measuring objective and subjective parameters.
Objective measures, such as increase in allergen-specific
IgG levels and decreased skin test reactivity, as measured
by skin test titration, are changes generally associated with
effective immunotherapy but, at present, are not practical
for routine clinical use. 147 Nonquantitative skin testing or
in vitro IgE antibody testing of patients during immunotherapy
is not recommended because it has not been
demonstrated that skin test reactivity (to a single dilution)
or specific IgE antibody levels correlate closely with a
patient’s clinical response. For that reason, most allergists
rely on subjective assessments, such as a patient’s report
that he or she is feeling better during a season previously
causing symptoms. Although subjective assessments are
the most common means by which physicians judge the
result of immunotherapy, they are not very reliable given
the strong placebo-like effect (Hawthorne effect) associated
with any treatment. A more objective means for determining
efficacy as validated in controlled clinical studies
is the use of clinical symptom scores and the amount of
medication required to control symptoms and maintain
peak flow rates or pulmonary function tests within acceptable
limits. Successful immunotherapy often results in
a reduction in medication. Sequential measurement of
disease-specific quality of life also might be helpful.
SAFETY OF IMMUNOTHERAPY
Reaction rates
Summary Statement 13: Published studies indicate that
individual local reactions do not appear to be predictive of
subsequent systemic reactions. However, some patients
with greater frequency of large local reactions might be at
an increased risk for future systemic reactions. C
Large local reactions associated with allergen immunotherapy
are fairly common, with a frequency ranging from
26% to 86% of injections. 179 Two retrospective studies
compared the effect of not adjusting immunotherapy dose
based on large local reactions on the immunotherapy systemic
reaction rate with dose-adjustment protocols. 179,180
There was a total of 12,464 injections administered with
a dose-adjustment protocol in the 2 studies compared
with 9542 injections administered with a no-dose-adjustment
protocol. Both studies found no statistical difference
between the dose-adjustment and no-dose-adjustment protocols
in terms of immunotherapy-induced systemic reactions.
Both authors concluded that local reactions were
poor predictors for subsequent systemic reactions, and
dose reductions for most local reactions are unnecessary.
However, a retrospective review of a large, multicenter,
allergy practice group’s database comparing the frequency
of large local reactions, defined as 25 mm or larger, in
patients who had experienced systemic reactions with age-,
sex-, and allergen sensitivity–matched control subjects
who had not had allergen immunotherapy systemic reactions
found the rate of large local reactions was 4 times
higher among the 258 patients who had subsequently
experienced a systemic reaction compared with those who
had never experienced a systemic reaction. 181 Patients who
had experienced systemic reactions had 1573 large local
reactions in 4460 visits (ie, 35.2% of visits) and 8081 injections
(ie, 19.5% of injections) compared with the matched
control group without systemic reactions who had 1388
large local reactions in 15,540 visits (8.9% per visit) and
26,259 injections (5.3% per injection; difference between
groups, P