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

J ALLERGY CLIN IMMUNOL
VOLUME 120, NUMBER 3
Cox et al S59
as high as 73% of patients, with the risk of such reactions
reduced to 27% by premedication in one study. 272 Most
reactions to rush immunotherapy are not severe, and the
most common systemic reaction is usually flushing. 273
Systemic reactions with rush schedules have been
reported to occur up to 2 hours after the final injection.
For that reason, individuals receiving rush immunotherapy
should remain under physician supervision for a
longer waiting period than the usual 30 minutes recommended
for conventional schedules (eg, 1.5-3 hours on the
day of allergen immunotherapy extract administration).
Rush protocols for administration of Hymenoptera
venom have not been associated with a similarly high
incidence of systemic reactions. 274-276,278,279
Premedication and weekly immunotherapy
Summary Statement 50: Premedication can reduce the
frequency of systemic reactions caused by conventional
immunotherapy. A
There is concern that antihistamines taken before each
injection with conventional immunotherapy might mask a
minor reaction that would otherwise alert a physician to an
impending systemic reaction. However, one randomized
controlled study demonstrated that premedication reduced
the frequency of severe systemic reactions caused by
conventional immunotherapy and increased the proportion
of patients who achieved the target maintenance dose. 280
One study that compared terfenadine premedication with
placebo premedication during rush VIT demonstrated
greater clinical efficacy in the terfenadine-premedicated
group in terms of subsequent responses to field stings or
sting challenge. 281 There was also a significant difference
in the systemic reaction rate between the 2 groups: 6
patients in the placebo-premedicated group had systemic
reactions, whereas none of the patients in the terfenadinepremedicated
group had systemic reactions (P 5 .012).
Unfortunately, patients might still have life-threatening
anaphylaxis despite premedication treatment. Because
many patients might take an antihistamine as part of their
overall allergy management, it is important to determine
whether they have taken it on the day that they receive
an allergen immunotherapy extract injection. For consistency
in interpretation of reactions, it also might be
desirable that they consistently either take their antihistamine
or avoid it on days when they receive immunotherapy.
Other attempts to reduce the occurrence of
systemic reactions, such as the addition of epinephrine
to the allergen immunotherapy extract or use of concomitant
corticosteroids, are not justified and might delay the
onset of a systemic reaction beyond the waiting time when
the patient is in the physician’s office, thus increasing
the risk.
Premedication with cluster and rush
immunotherapy
Summary Statement 51: Premedication should be given
before cluster and rush immunotherapy with aeroallergens
to reduce the rate of systemic reactions. A
Premedication with a nonsedating antihistamine (loratadine)
2 hours before the first injection of each visit
reduced both the number and severity of systemic reactions
during cluster immunotherapy. 267 Premedication
with a 3-day course of prednisone, an H 1 histamine receptor
antagonist, and an H 2 histamine receptor antagonist before
rush immunotherapy with inhalant allergens reduced
the risk of a systemic reaction from approximately 73% to
27% of patients. 272 In one study designed to investigate
the effect of 12 weeks of premedication with a humanized
monoclonal anti-IgE antibody (omalizumab) on the safety
and efficacy of rush immunotherapy, there was a 5-fold
decrease in the risk of anaphylaxis in the group premedicated
with omalizumab compared with the placebo premedication
group. 282
There are anecdotal reports of reductions in systemic
reaction rates with the addition of a leukotriene receptor
antagonist, but there have been no published studies.
Because the risk of a systemic reaction from rush VIT is
relatively low, routine premedication before rush VIT is
usually unnecessary. 274,276,278,279 In a study evaluating
premedication with antihistamines and steroids for rush
immunotherapy with imported fire ant venom, there was
no statistically significant differences in the systemic reaction
rates between the premedication and placebo premedication
group (3.6% of the premedication group vs 6.7% of
the placebo group, P 5 .87). 157
Maintenance schedules
Summary Statement 52: Once a patient reaches a
maintenance dose, the interval between injections often
can be progressively increased as tolerated up to an
interval of up to 4 weeks for inhalant allergens and up to
8 weeks for venom. Some individuals might tolerate
longer intervals between maintenance dose injections. A
Once a patient who is receiving inhalant allergen
immunotherapy reaches a maintenance dose, an interval
of 2 to 4 weeks between injections is recommended,
provided clinical improvement is maintained. Some individuals
might tolerate longer intervals between maintenance
dose injections.
The interval between venom injections can be safely
increased up to 8 weeks in some patients without loss of
efficacy. In other patients, greater efficacy, fewer reactions,
or both might occur with shorter intervals between
injections. Therefore the interval between allergen immunotherapy
injections should be individualized to provide
the greatest efficacy and safety for each patient.
Continuing care
Time course of improvement. Summary Statement 53:
Clinical improvement can be demonstrated very shortly
after the patient reaches a maintenance dose. A
Clinical improvement can be demonstrated very shortly
after the patient reaches a maintenance dose. 24,134,143,277
Improvement might not be observed for a number of reasons,
including (1) failure to remove significant allergenic
exposures (eg, a cat), (2) exposure to high levels of