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

S66 Cox et al
J ALLERGY CLIN IMMUNOL
SEPTEMBER 2007
FIG 4. Sample set of color-coded vials of allergen vaccine.
There is currently no FDA-approved formulation for
sublingual immunotherapy in the United States at this
time, and this modality should be considered investigational.
Current investigation of sublingual immunotherapy
should not be confused with low-dose sublingual immunotherapy
based on provocation neutralization testing or
Rinkel-type skin testing.
Intranasal immunotherapy
Summary Statement 75: Intranasal immunotherapy is
undergoing evaluation in children and adults with allergic
rhinitis, but there is no FDA-approved formulation for this
modality in the United States. B
Based on controlled, well-designed studies, intranasal
immunotherapy has been shown to improve the nasal
symptoms of rhinitis. 330 Intranasal dry powder extract immunotherapy
has been studied in grass, 330 birch, 331 P judaica,
332-334 and house dust mite 335 allergy. Clinical
efficacy was noted in all of these studies. Nasal reactivity
to allergen challenge was reduced, and only minor side effects
were noted in 2 of the above studies. A 3-year study
with P judaica reported to provide persistent benefits for
up to 12 months after conclusion of allergen immunotherapy.
333 Local administration of nasal allergen in an aqueous
solution for immunotherapy might be limited by the
local side effects. Further studies in both pediatric and
adult groups are needed. In human studies the antigen
has been noted to appear in the serum within 15 to 30 minutes
of administration, with a peak level occurring within
2 to 3 hours. 315 Some allergens have been reported to be
retained in the nasal mucosa for up to 48 hours after administration.
Intranasal immunotherapy is not currently
available in the United States but has gained some acceptance
in other parts of the world.
Immunotherapy techniques that are not
recommended
Summary Statement 76: Low-dose immunotherapy,
enzyme-potentiated immunotherapy, and immunotherapy
(parenteral or sublingual) based on provocation-neutralization
testing are not recommended. D
Low-dose regimens, including coseasonal low-dose
immunotherapy for aeroallergens and the Rinkel lowdose
titration techniques, are not effective. 27,28 Immunotherapy
based on provocation–neutralization testing with
food and aeroallergens and enzyme-potentiated desensitization
is not effective. 336
FUTURE TRENDS IN IMMUNOTHERAPY
Therapy with aeroallergen extracts will become more
uniform (as is the current practice for insect venoms) as
greater numbers of biologically standardized allergen
extracts become available. The actual number of commercially
available allergen extracts will be reduced based on
consensus agreements about the regional prevalence of
aeroallergens, their cross-allergenicity, and the relevance of
their effect on human health in specific locales. Novel routes
for more effective, convenient, and safer allergen immunotherapy
are being investigated throughout the world.
For example, the sublingual route of administering
allergen immunotherapy has been studied extensively in
Europe. A meta-analysis confirmed its clinical effectiveness
in allergic rhinitis, 302 and it has been reported to be
effective in asthma as well. 337 Sublingual immunotherapy
appears to have a very low risk of serious life-threatening
systemic side effects, which might allow for home administration.
324,338 In some studies the clinical benefits of sublingual
immunotherapy were not significant until the
second year of treatment, 306,339 and comparisons suggest
that the magnitude of the clinical benefit of sublingual immunotherapy
might not be as great as that of subcutaneous
immunotherapy. 311
Trials with non–IgE-binding peptides containing T-cell
stimulating peptides have been reported. 340 Site-directed
mutagenesis has produced allergens with decreased
IgE-binding capacity without decreased T-cell
responses. 341,342
Immunostimulatory sequences mimicking bacterial
and viral DNA have been prepared that stimulate the
innate immune system to direct T-cell responses toward