Available via license: CC BY-NC 4.0
Content may be subject to copyright.
ORIGINAL ARTICLE
The efficacy assessment of a self-administered immunotherapy protocol
Frederick M. Schaffer, MD1,2 , Larry M. Garner, BA1, Myla Ebeling, RA3, Jeffrey M. Adelglass, MD4,
Thomas C. Hulsey, ScD3and Andrew R. Naples, BS1
Background: We previously reported the safety of a self-
administered subcutaneous immunotherapy (SCIT) proto-
col. Here we report the results of the retrospective efficacy
trial of the United Allergy Service (UAS) self-administered
SCIT protocol. We hypothesized that by utilizing a slow
SCIT buildup phase, designed to aain recommended aller-
gen concentrations on a cumulative basis, efficacious out-
comes and clinical relevance would be achieved.
Methods: We enrolled 60 SCIT patients and 56 control pa-
tients. The study contrasted baseline and treatment period
combined symptom plus medication scores (CSMS) as the
primary outcome measure and rhinoconjunctivitis quality
of life questionnaire (RQLQ) scores as the secondary study
outcome measure. Changes in pollen counts were also ex-
amined with regard to effects on these efficacy parame-
ters.
Results: The treatment group showed significantly im-
proved CSMS (standardized mean difference [SMD]: −1.57;
95% confidence interval [CI], −1.97 to −1.18; p<0.001)
and RQLQ (SMD: −0.91; 95% CI, −1.23 to −0.59; p<
0.001). These treatment group outcome measures were
respectively improved by 33% and 29% compared to
baseline and greater than 40% in comparison to the con-
trol group (p<0.0001). Significant results were also shown
when examining these outcome measures with regards to
either monotherapy or poly-allergen SCIT. Furthermore,
a comparison to recent meta-analyses of SCIT studies
showed equivalent efficacy and clinical relevance. Assess-
ment of pollen counts during the baseline and treatment
periods further corroborated the efficacy of the UAS SCIT
protocol.
Conclusion: These efficacy results, and our previous safety
results, show that a carefully designed and implemented
self-administered SCIT protocol is efficacious and safe. C
2015 The Authors International Forum of Allergy & Rhinology
published by Wiley Periodicals, Inc., on behalf of ARS-AAOA,
LLC.
This is an open access article under the terms of the Cre-
ative Commons Attribution NonCommercial License, which
permits use, distribution and reproduction in any medium,
provided the original work is properly cited and is not used
for commercial purposes.
Key Word s:
allergic rhinitis; allergy immunotherapy; allergy injections;
subcutaneous immunotherapy; aeroallergens
HowtoCitethisArticle:
Schaffer FM, Garner LM, Ebeling M, Adelglass JM, Hulsey
TC, Naples AR. The efficacy assessment of a self-
administered immunotherapy protocol. Int Forum Allergy
Rhinol. 2016;6:148–155.
In contrast to pharmacotherapy, allergen immunotherapy
(IT) is the only therapeutic modality that specifically ad-
1United Allergy Services (UAS), San Antonio, TX; 2Division of Pediatric
Pulmonary, Allergy and Immunology, Medical University of South
Carolina, Charleston, SC; 3Division of Pediatric Epidemiology, Medical
University of South Carolina, Charleston, SC; 4Allergy Testing and
Treatment Center, Plano, TX
Correspondence to: Frederick M. Schaffer, MD, United Allergy Services,
100 NE Loop 410, Suite 250, San Antonio, TX 78216; e-mail:
Fred.Schaffer@UnitedAllergy.com
Additional Supporting Information may be found in the online version of this
article.
Potential conflict of interest: F.M.S., A.R.N., and L.M.G. are employees of
UAS. T.C.H. and M.E. are paid by UAS for their statistical services.
Received: 5 April 2015; Revised: 26 June 2015; Accepted: 18 August 2015
DOI: 10.1002/alr.21653
View this article online at wileyonlinelibrary.com.
dresses the central pathophysiology of allergic rhinitis and
possibly diminishes the development of allergic asthma and
severity of other preexisting allergic comorbidities.1–11
Several studies, including a recent study by this
group, have showed safe outcomes for carefully designed
self-administered subcutaneous immunotherapy (SCIT)
protocols.12–17 A recent criticism hypothesized that 1 set
of these safety outcomes was achieved by utilizing subther-
apeutic allergen concentrations and thus, the attainment of
clinical efficacy was questioned.18 Therefore, the demon-
stration of clinical efficacy is a salient issue, particularly for
self-administered SCIT protocols.
The majority of SCIT prescribed in the United States uses
several allergen extracts to compliment the patient with
multiple sensitivities.19–21 Consistent with this commonly
prescribed therapeutic approach in the United States, we
report the findings of a SCIT protocol designed for patients
International Forum of Allergy & Rhinology, Vol. 6, No. 2, February 2016 148
Efficacy of self-administered immunotherapy
with multiallergen sensitivities. Specifically, we present and
discuss the results of a self-administered SCIT retrospective
efficacy study using the United Allergy Services (UAS) im-
munotherapy protocol.
Patients and methods
Patients
All subjects were diagnosed with seasonal or seasonal plus
perennial allergic rhinitis (AR) as described.22 Patients with
contraindications consistent with the current recommenda-
tions for allergy skin prick testing (SPT) and SCIT utiliza-
tion were excluded.2, 22 All patients underwent SPT utiliz-
ing relevant extracts consistent with standard practices.2, 22
Both male and female patients aged 18 to 65 years with
diagnosed AR were openly enrolled in the study. Patients
who were enrolled and opted for SCIT were deemed treat-
ment patients and those that declined SCIT were deemed
control patients.
Study design
To control for geographic differences, patients were pri-
marily recruited from clinics located in Dallas, TX, and
San Antonio, TX. Research personnel were blinded to pa-
tient identification, age, gender, and primary care clinic
affiliation. The study design, informed consent, and execu-
tion were approved by the Salus Independent Review Board
(IRB) (Austin, TX).
All study subjects were allowed to continue oral and top-
ical antihistamines and nasal steroids prescribed by their
physician. Study subjects using systemic steroids were ex-
cluded. Individuals enrolled in the study completed vali-
dated questionnaires as discussed below (see Assessment).
UAS immunotherapy protocol
Immunotherapy formulation guidelines were in accor-
dance with published recommendations.2, 22–27 Due to
the documented increased risk of systemic reactions (SR)
during the immunotherapy buildup phase (ie, escalation
phase),25–28 the UAS protocol was designed to complete the
buildup phase over a 6-month period. Also, based upon
the administration frequency and allergen concentrations
used, cumulative allergen dosing is equivalent to current
recommendations.2, 12 A more detailed description of the
UAS SCIT protocol has been recently published.12
Assessment
Enrolled subjects completed validated questionnaires
for rhinoconjunctivitis symptom scores (SS) in ac-
cord with both the U.S. Food and Drug Administra-
tion (FDA) and World Allergy Organization (WAO)
recommendations.29–31 The medication scores (MS) par-
alleled the methods of Stelmach et al.32 The aggregate
of the SS and the MS (CSMS) followed previously uti-
lized methods.32–36 The Rhinoconjunctivitis Quality of Life
Questionnaire (RQLQ) used consists of 28 queries divided
into 7 domains.37
These questionnaires were initially completed at the end
of the baseline year of therapy (2010 to 2011). During
this period, all study participants were undergoing pharma-
cotherapy and avoidance therapy only. After undergoing a
further 12 or more months of immunotherapy (2011 to
late 2012), the second set of surveys were completed. This
survey methodology is consistent with the format used in
several previous trials.38–41 (See the online Supporting In-
formation for the questionnaires.)
Statistical methods
For each study subject, their SS, MS, CSMS, and RQLQ
were averaged for both the baseline and the follow-up as-
sessments. The difference in mean scores between baseline
and follow-up was obtained and within group differences
were assessed by use of a paired Student ttest. Group dif-
ferences between mean scores at baseline and at follow-up
were assessed by use of the Student ttest. Standardized
mean differences (SMDs) were computed as the mean dif-
ference divided by the standard deviation of the mean dif-
ference. The SMD inclusion was so that the results from
this project could be compared to other published reports
which may have used modified assessments of symptom
and medication scores.
Adverse events, safety, and compliance
determination
Patients were required to report all suspected adverse events
to their primary care clinics as soon as possible and to cease
continued treatment until evaluated and provided guidance
by their physician.
To promote safety and compliance, all patients were only
given a single unit-dose vial set and a preprinted IT injec-
tion log book that enumerated all required doses to utilize.
Patients were instructed to maintain the injection log and to
record any pertinent events related to the injections. All pa-
tients were interviewed and their logs were reviewed when
they returned to the clinic to acquire their next unit-dose
vials.
Pollen count analyses
Atmospheric sampling for aeroallergens was performed
and reported by certified staff through the American
Academy of Allergy, Asthma and Immunology Aeroaller-
gen Network. Aeroallergen samplers used were approved
by the National Allergy Bureau (NAB) and identifica-
tion/measurements met NAB requirements.
The grass pollen seasons were determined by examining
pollen counts of greater than 15 grains/m3for 3 consecutive
days, which defined the season starting date. Whereas, grass
pollen counts that were less than 15 grains/m3for 3 consec-
utive days defined the season ending date.42–44 Weed-based
and tree-based pollen seasons were determined by exam-
ining the raw data for respective pollen counts of greater
than 20 grains/m3for 3 consecutive days, which defined
the season starting date, whereas respective pollen counts
149 International Forum of Allergy & Rhinology, Vol. 6, No. 2, February 2016
Schaffer et al.
TABLE 1. Characteristics of treatment and control patients
Treatment Control
Sex (n)
Male 24 5
Female 36 51
Race (n)
White 37 34
African American 12 7
Hispanic 2 7
Other 9 8
Age (years), mean ±SD 37.09 ±13.92
Duration of therapy (years),
mean ±SD
1.22 ±0.27
Administered SCIT-based
aeroallergen extracts
(n), mean ±SD
9.08 ±1.84 N/A
SCIT =subcutaneous immunotherapy; SD =standard deviation.
that were <20 grains/m3for 3 consecutive days defined the
season ending date. The delineation of pollen seasons by
these levels are consistent with NAB-defined “moderate”
pollen exposure.42–44
Results
Protocol compliance
One of the 60 individuals in the SCIT treatment group did
not comply with the specified treatment protocol and that
individual was excluded from the study. Another treatment
group participant was compliant for 75% of scheduled in-
jections and he was not excluded from study participation.
All other treatment and control group study participants
were fully compliant.
Adverse events and systemic disorders
One study subject in the SCIT treatment group reported
a WAO grade II SR.45 After medical assessment and
advisement, this patient’s SCIT protocol was appropri-
ately addressed.2His SCIT regimen subsequently continued
without further clinical incident. Three other participants
in the SCIT treatment group reported local reactions with-
out sequelae. There were no reported adverse events by
subjects in the control group.
Patient demographics
The patient demographics are shown in Table 1.
Identified allergies
The most common allergies manifested by both the treat-
ment and control groups are: cedar and oak tree pollens
(>60% of treatment group and 40% of controls); Bermuda
and Timothy grass pollen (>62% of treatment group and
58% of controls); ragweed pollen (57% of treatment group
and 45% of controls); and dust mites (>67% of treatment
group and 57% of controls). Also, allergies to oak tree
pollen, Timothy grass pollen, and dust mites are shared by
35% of the treatment group and 27% of the control group.
Rhinoconjunctivitis SS
Assessment showed that individuals in the treatment group
(ie, SCIT therapy) experienced a 35% SS improvement over
their baseline scores. The treatment group’s SS improve-
ment in comparison to that of the control group is con-
sistent with a >45% improvement (p<0.0001; data not
shown). Also, the control group experienced a significant
increase in SS in year 2 vs year 1 of this study (data not
shown; p=0.05).
MS
MS analyses showed that the treatment group had a 30%
decrease in medication use (data not shown, p<0.001).
Also, there is a significant decrease in the MS of the treat-
ment group in comparison to the control group’s scores
(p<0.001). In contrast, the control group experienced a
significant increased use of medications in the second vs
the initial study year (paired SMD of −1.57; p<0.0001,
Table 2). Furthermore, there was a 33% improvement for
the treatment group with respect to baseline results and a
>40% improvement in comparison to the control group
(p<0.001).
The treatment group’s RQLQ showed a 29% improve-
ment in comparison to baseline results and a 42% improve-
ment in comparison to the control group (p<0.0001). In
contrast, the control group results did not show a signifi-
cant RQLQ SMD score change during the intervals under
assessment (p=0.7, Table 2). A comparison of RQLQ
scores for each of the 7 domains further showed that the
treatment group attained significant improvement in 6 of
the 7 domains (data not shown).
From a multiallergen perspective, Table 2 depicts the
CSMS and RQLQ SMD differences for patient groups with
common allergies to oak trees, dust mites, and Timothy
grass. In a similar manner, Table 2 shows the results for
sizeable patient populations manifesting respective com-
mon allergies to ragweed and dust mites, respectively. The
CSMS results for the treatment groups with common al-
lergies to oak tree, dust mites, and Timothy grass, or the
individual allergens of ragweed or dust mites (all in Table
2) show significant improvement. In contrast, each respec-
tive control group showed significant increases (or wors-
ening) of their CSMS scores. With regard to other com-
binations of manifested allergies, either shared dual-pollen
or single-pollen allergies, similar results were evident (data
not shown).
The RQLQ SMD results (Table 2) show significant
improvement for subjects in the treatment group (mean
International Forum of Allergy & Rhinology, Vol. 6, No. 2, February 2016 150
Efficacy of self-administered immunotherapy
TABLE 2. Differences in CSMS and RQLQ for the treatment and control groups
nDiff: T2-T1 Paired SMD CI pa
Medication use in the second vs the initial study year
CSMS
Control 56 0.56 0.34 −0.06 to 0.73 0.01
Treatment 60 −1.84 −1.57 −1.97 to −1.18 <0.0001
RQLQ
Control 56 0.07 0.05 −0.32 to 0.41 0.7
Treatment 60 −1.24 −0.91 −1.23 to −0.59 <0.0001
Common allergies to oak, dust mite, and Timothy grass
CSMS
Control 48 0.62 0.39 −0.02 to 0.81 0.009
Treatment 56 −1.83 −1.54 −1.95 to −1.14 <0.0001
RQLQ
Control 48 0.19 0.13 −0.27 to 0.52 0.39
Treatment 56 −1.22 −0.87 −1.20 to −0.54 <0.0001
Common allergies to ragweed
CSMS
Control 22 0.73 0.49 0.08 to 1.06 0.03
Treatment 34 −1.86 −1.46 −2.02 to −0.91 <0.0001
RQLQ
Control 22 0.11 0.07 −0.54 to 0.69 0.7
Treatment 34 −1.20 −0.83 −1.27 to −0.39 <0.0001
Common allergies to dust mites
CSMS
Control 47 0.59 0.37 −0.05 to 0.79 0.01
Treatment 40 −1.86 −1.70 −2.21 to −1.20 <0.0001
RQLQ
Control 47 0.18 0.12 −0.29 to 0.52 0.4
Treatment 40 −1.16 −0.79 −1.16 to −0.41 <0.0001
aBold values are significant.
CI =95% confidence interval; CSMS =combined symptom plus medication scores; Diff: T2-T1 =difference in average CSMS and RQLQ scores from final patient
surveys in comparison to initial or baseline surveys; Paired SMD =standard mean difference calculated per patient from baseline survey to follow-up survey; RQLQ =
rhinoconjunctivitis quality of life questionnaire.
improvement of 28% over baseline and a >40% improve-
ment with respect to the control group). The control group
results showed no significant change in RQLQ scores dur-
ing the study period. With regard to other allergy combi-
nations, similar results were evident (data not shown).
Pollen count assessment
Figure 1A and B show respective total seasonal pollen
counts for both metropolitan locations in which the
participants reside. These figures display pollen counts
for the periods encompassing the baseline year (2010 to
2011) and the second year of study (2011 through 2012
inclusive).
An assessment of the pollen results available for the years
of 2011 through 2012 in comparison to 2010 to 2011 in
San Antonio show that total seasonal pollen counts were
relatively unchanged for mountain cedar tree and oak tree
(Fig. 1A), while in contrast, a significant decrease in to-
tal pollen counts for ragweed occurred. Furthermore, there
151 International Forum of Allergy & Rhinology, Vol. 6, No. 2, February 2016
Schaffer et al.
FIGURE 1. (A) Pollen counts in San Antonio for 2010 through 2012. (B)
Pollen counts in Dallas for 2010 through 2012. Bars represent total pollen
count for the specified pollen season. Total season pollen count is on a log10
scale.
was increased grass pollen counts documented (Fig. 1A).
Analysis of the Dallas pollen seasons reveals that during
this same time period, unchanged pollen counts for oak
tree and mountain cedar tree pollen were evident (Fig. 1B).
In contrast, significant increased total grass pollen and rag-
weed pollen counts were recorded.
Discussion
In this study we assayed the efficacy of the UAS poly-
allergen SCIT protocol by examining changes in the study
outcome measures of CSMS as the primary measure and
RQLQ results as the secondary outcome measure.
The total SS, MS, CSMS, and RQLQ scores were signif-
icantly improved for those undergoing SCIT (ie, treatment
group) when examined at a mean of 1.22 years of therapy
in comparison to baseline data and the control group scores
(Table 2). When analyses focused on the 6 most common
individual allergen sensitivities (cedar tree, oak tree, rag-
weed mix, Bermuda grass, Timothy grass, and dust mites,
in part shown in Table 2) or combinations shared by both
groups (in part shown in Table 2), similar significant im-
provement in the respective treatment group CSMS and
RQLQ results were shown in comparison to baseline and
control group results.
Because statistical significance may not equate to clinical
relevance, several means of evaluating clinical significance
or relevancy have historically been used.46–48 For non-
placebo controlled studies (eg, current study), Erekosima
et al.46 determined that a difference of ࣙ15% in the ef-
ficacy outcome measures in comparison to the control
group were considered clinically significant. Furthermore,
the WAO taskforce recommended that efficacy study out-
comes of 20% or more than placebo are consistent with
clinical significance.47 Thus, the current study changes in
the primary efficacy outcome measures are both statistically
significant and clinically relevant.
The RQLQ results showed a significant treatment group
improvement compared to its baseline results and in com-
parison to the control group results. In order to address
clinical significance, a change in RQLQ of greater than ±
0.5 surpasses the threshold of clinical relevance and is evi-
dent in the current study treatment group (with an RQLQ
SMD of −0.91).29, 49 It is understood that differences in
study design, methodology used, and scoring methods war-
rant careful consideration in contrasting study results. In a
review by Nelson,19 the majority of published SCIT effi-
cacy studies to date include only monotherapy trials. Thus,
in our comparisons several of the trials are monotherapy
studies. A comparison of the current study CSMS-SMD to
the majority of studies (ie, those with study populations
>20 subjects) referenced by Dretzke et al.10 and DiBona
et al.50 is illustrated in Figure 2A.51–58 Figure 2A shows
(study population) weighted CSMS-SMD with 95% confi-
dence intervals (CIs) for the 8 studies reported by Dretzke
et al.10 and DiBona et al.50 (where the mean of all studies is
depicted in red), and the CSMS-SMD for the current UAS
protocol study (depicted in blue).51–58 Evident in Figure 2A
is the statistical equivalency of our results with those re-
viewed by Dretzke et al.10 and DiBona et al.50–58 When
assessing the CSMS-SMD for the grouped or individual
allergens reviewed in this study, the same statistical equiv-
alency of our results is evident (data not shown).
For analysis of RQLQ, Figure 2B shows (study pop-
ulation) weighted RQLQ-SMD with 95% CIs for the 8
studies reported by Dretzke et al.10 and the UAS RQLQ-
SMD results.56–63 Evident in this figure is the statistical
equivalency of our results with those reviewed by Dretzke
et al.10, 56–63 When assessing the RQLQ-SMD for the
grouped or individual allergens reviewed in this study, the
same statistical equivalency of our results is also noted
(data not shown).
Therefore, the results of our primary and secondary out-
come measures show that the utilization of the UAS pro-
tocol has statistically equivalent efficacy and comparable
International Forum of Allergy & Rhinology, Vol. 6, No. 2, February 2016 152
Efficacy of self-administered immunotherapy
FIGURE 2. (A) CSMS results compared to previous published
results.10,50–58 (B) RQLQ results compared to previous published
results.10,56–63 Blue data point is the SMD for the UAS SCIT trial. The red
data point is the mean SMD for all studies enumerated in the graph. CI =
confidence interval; CSMS =combined symptom plus medication scores;
RQLQ =rhinoconjunctivitis quality of life questionnaire; SCIT =subcuta-
neous immunotherapy; SMD =standardized mean difference; UAS =United
Allergy Service.
clinical relevancy to recently conducted meta-analyses of
both American and European based SCIT studies.
A direct correlation has been reported between the level
of pollen counts and the corresponding SS and MS (the
components of the CSMS) among affected individuals.64
Because total pollen counts were either unchanged or in-
creased during the second year of the study in Dallas (Fig.
1B), depending on the individual’s allergen sensitivities,
their SS and CSMS scores would be expected to be sim-
ilar or worse during the second year in comparison to the
first year of the study. Specifically, each control group’s (eg,
Dallas and San Antonio) CSMS worsened from year 1 to
year 2 of the study while the treatment groups’ outcomes
(in both Dallas and San Antonio) significantly improved (as
shown for all study subjects; see Table 2). Thus, for the sub-
jects enrolled in Dallas only, the treatment group’s improve-
ment (eg, SS and CSMS), in contrast to the geographically
matched control group, further corroborates the efficacy
of the UAS SCIT protocol employed in this study. With
regard to the study participants in San Antonio, the find-
ings show that in an environment of increasing grass and
unchanged tree pollen counts, the improved study parame-
ters (eg, SS and CSMS) also corroborate the efficacy of the
UAS SCIT protocol. The lower total ragweed pollen count
in year 2 could have contributed to the improved SS and
CSMS exhibited by the San Antonio treatment group. How-
ever, without a parallel efficacy measurement improvement
showed by the control group, the treatment group’s efficacy
measurement improvement is more likely a consequence of
their clinical response to SCIT therapy. Furthermore, unlike
the respective control group, the San Antonio and Dallas
treatment groups’ medication utilization (ie, MS) signifi-
cantly decreased in conjunction with specific pollen-related
improved SS, which further corroborates the efficacy of the
immunotherapy protocol used.43
This corroboration of the efficacy of the UAS SCIT proto-
col holds under the assumption that exposure to perennial
allergens are not significantly changed throughout the study
period. Similar assumptions were considered in the analy-
ses of monotherapy grass and ragweed studies in which
78% to 90% of the study subjects were polysensitized to
other allergens.20, 21 As noted by those authors, the major-
ity of U.S. patients manifest poly-allergen sensitivities and
are treated with poly-allergen SCIT (as exemplified in the
present study).
In our recently published study of the largest population
of self-administered SCIT patients studied to date, safety
results were derived from the medical review of approx-
imately 24,000 patients who had self-administered over
2 million SCIT injections. The systemic reaction rate was
only 0.16% per individual and 0.002% per injection in
comparison to significantly higher office-based rates of ap-
proximately 4% to 14%.12 Consistent with these results,
several other reports have previously documented the safety
of self-administered or home-based SCIT.13–17 The authors
concluded that the low systemic reaction rates reported
showed that home-based immunotherapy was safe.13–17
The efficacy and safety of the UAS SCIT protocol are
hypothesized to be due to: a slower than traditional SCIT
buildup (ie, escalation) phase that attains recommended
allergen concentrations on a cumulative dosing basis, a
preselection of low-risk patients, and emphasis on pa-
tient education.12 The rate of allergen dose increase dur-
ing the buildup phase is considered a prominent factor in
immunotherapy-based systemic reactions.9, 65–67 Consistent
with these principles, the UAS protocol was designed to in-
corporate a slow buildup phase in order to diminish the
associated high frequency of systemic reactions.27
The cumulative administered allergen dose has been pos-
tulated to be the significant factor in SCIT efficacy.3, 4 Al-
though we hypothesize that the efficacy of the UAS SCIT
protocol is dependent upon cumulative allergen dosing as
exemplified by the results of previous IT reports, further
studies are warranted to substantiate this thesis.68–72
A weakness in this study, as evident in other retrospective
studies, is the potential occurrence of recall bias.73 In order
to minimize the effects of this potential bias, it has been rec-
ommended to use standardized well-structured surveys.73
Consistent with those recommendations, we have employed
well-structured questionnaires for assessment of the SS,
MS, CSMS, and the validated RQLQ questionnaire.37
153 International Forum of Allergy & Rhinology, Vol. 6, No. 2, February 2016
Schaffer et al.
Previously, several immunotherapy studies have encom-
passed similar retrospective periods of analysis, and other
studies have used significantly longer periods with valid
results despite possible recall bias.38–41
Conclusion
In conclusion, our results show significant improvement in
SS, MS, CSMS, RQLQ, and clinical relevancy associated
with the use of the UAS SCIT protocol. These efficacy
results, and our previously reported safety results,
show that a carefully designed and implemented self-
administered SCIT protocol is both efficacious and safe.
Acknowledgments
We thank Sylvana Research in San Antonio, TX, for sup-
plying the pollen counts for San Antonio, and the Allergy
Testing and Treatment Center in Dallas, TX, for supplying
the pollen counts for the Dallas/Fort Worth area.
References
1. Soyer OU, Akdis M, Akdis CA. Mechanisms of sub-
cutaneous allergen immunotherapy. Immunol Allergy
Clin North Am. 2011;31:175–190.
2. Cox L, Nelson H, Lockey R. Allergen immunother-
apy: a practice parameter third update. J Allergy Clin
Immunol. 2011;127(1 Suppl):S1-S55.
3. Eng PA, Borer-Reinhold M, Heijnen IAFM, et al.
Twelve-year follow-up after discontinuation of pre-
seasonal grass pollen immunotherapy in childhood.
Allergy. 2006;61:198–201.
4. Jacobsen L, Niggemann B, Dreborg S, et al. Specific
immunotherapy has long-term preventive effect of sea-
sonal and perennial asthma: 10-year follow-up on the
PAT study. Allergy. 2007;62: 943–948.
5. Durham SR, Walker SM, Varga EM, et al. Long-
term clinical efficacy of grass-pollen immunotherapy.
N Engl J Med. 1999;341:468–475.
6. Schneider L, Tilles S, Lio P, et al. Atopic dermatitis:
a practice parameter update 2012. J Allergy Clin Im-
munol. 2013;131:295–299.
7. Caraballo JMS, Villa RC. Clinical and im-
munological changes of immunotherapy in pa-
tients with atopic dermatitis: randomized controlled
trial. ISRN Allergy. 2012;2012:Article ID 183983.
doi:10.5402/2012/183983.
8. Panjo GB, Caminiti L, Vita D, et al. Sublin-
gual immunotherapy in mite-sensitized children
with atopic dermatitis: a randomized, double-blind,
placebo-controlled study. J Allergy Clin Immunol.
2007;120:164–170.
9. Lin MS, Tanner E, Lynn J, et al. Nonfatal systemic
allergic reactions induced by skin testing and im-
munotherapy. Ann Allergy. 1993;71:557–562.
10. Dretzke J, Meadows A, Novielli N, et al. Subcuta-
neous and sublingual immunotherapy for seasonal al-
lergic rhinitis: a systemic review and indirect compar-
ison. J Allergy Clin Immunol. 2013;131:1361–1366.
11. White P, Smith H, Baker N, et al. A symptom control
in patients with hay fever in UK general practice: how
well are we doing and is there a need for allergen im-
munotherapy? Clin Exp Allergy. 1998;28:266–270.
12. Schaffer FM, Naples AR, Ebeling M, Hulsey TC,
Garner LM. The safety of self-administered allergen
immunotherapy during the buildup and maintenance
phases. Int Forum Allergy Rhinol. 2015;5:149–156.
13. Cook PR, Bryant JL, Davis WE, et al. Systemic re-
actions to immunotherapy: the AAOA Morbidity
and Mortality Survey. Otolaryngol Head Neck Surg.
1994;110:487–493.
14. Wells JH. Home allergenic extract administration. J
Allergy Clin Immunol. 1995;95:1061–1063.
15. Falliers CJ. At-home administration of allergenic ex-
tracts. J Allergy Clin Immunol. 1995;95:1061–1063.
16. Filley WV. Safety of home immunotherapy. J Allergy
Clin Immunol. 2006;117:S159.
17. Hurst DS, Gordon BR, Fornadley JA, et al. Safety of
home-based and office allergy immunotherapy: a mul-
ticenter prospective study. Otolaryngol Head Neck
Surg. 1999;121:553–561.
18. Cox L, Aaronson D, Casale TB, et al. Allergy im-
munotherapy safety: location matters! J Allergy Clin
Immunol Pract. 2013;1:455–457.
19. Nelson HS. Multiallergen immunotherapy for aller-
gic rhinitis and asthma. J Allergy Clin Immunol.
2009;123:763–769.
20. Cox LS, Casale TB, Nayak AS, et al. Clinical effi-
cacy of 300IR 5-grass pollen sublingual tablet in a US
study: the importance of allergen-specific serum IgE. J
Allergy Clin Immunol. 2012;130:1327–1334.
21. Skoner D, Gentile D, Bush R, et al. Sublingual im-
munotherapy in patients with allergic rhinoconjunc-
tivitis caused by ragweed pollen. J Allergy Clin Im-
munol. 2010;125:660–666.
22. Bernstein LI, Li JT, Bernstein DI, et al. Allergy di-
agnostic testing: an updated practice parameter. Ann
Allergy Asthma Immunol. 2008;100:S1-S148.
23. Grier TJ, LeFevre DM, Duncan EA, et al. Stability of
standardized grass, dust mite, cat, and short ragweed
allergens after mixing with mold or cockroach ex-
tracts. Ann Allergy Asthma Immunol. 2007;99:151–
160.
24. Esch RE, Grier TJ. Allergen compatibilities in extract
mixtures. Immunol Clin North Am. 2011;31:227–
239.
25. Bernstein DI, Wanner M, Borish L, et al. Twelve-
year survey of fatal reactions to allergen injections
and skin testing: 1990–2001. J Allergy Clin Immunol.
2004;113:1129–1136.
26. Reid MJ, Lockey RF, Turkeltaub PC, et al. Survey of
fatalities from skin testing and immunotherapy 1985–
1989. J Allergy Clin Immunol. 1993;91:6–15.
27. Epstein TG, Liss GM, Murphy-Berendts K, et al.
Immediate and delayed-onset systemic reactions
after subcutaneous immunotherapy injections:
ACAAI/AAAAI surveillance study of subcuta-
neous immunotherapy–year 2. Ann Allergy Asthma
Immunol. 2011;107:426–431.
28. Cox L, Li JT, Nelson HS, et al. Allergen immunother-
apy: a practice parameter second update. J Allergy
Clin Immunol. 2007;120:S25-S85.
29. Pfaar O, Demoly P, Gerth van Wijk R, et al. Rec-
ommendations for the standardization of clinical out-
comes used in allergen immunotherapy trials for al-
lergic rhinoconjunctivitis: EAACI position paper. Al-
lergy. 2014;69:854–867.
30. U.S. Department of Health and Human Services,
Food and Drug Administration Center for Drug Eval-
uation and Research (CDER). Guidance for Industry
Allergic Rhinitis: Clinical Development Programs for
Drug Products. Draft Guidance, 2000. Rockville,
MD: U.S. Food and Drug Administration; 2000.
http://www.fda.gov/downloads/drugs/guidancecomp
lianceregulatoryinformation/guidances/ucm071293
.pdf. Accessed September 15, 2015.
31. European Medicine Agency. Committee for Medicinal
Products for Human Use (CHMP). Guideline on the
Clinical Development of Products for specific Im-
munotherapy for the Treatment of Allergic Diseases.
London, UK: European Medicine Agency; 2008.
http://www.ema.europa.eu/docs/en_GB/document
_library/Scientific_guideline/2009/09/WC500003605
.pdf. Accessed September 15, 2015.
32. Stelmach I, Kaluzinska-Parzyszek I, Jerzynska J, et al.
Comparative effect of pre-co-seasonal and continuous
grass sublingual immunotherapy in children. Allergy.
2012;67:312–320.
33. Nelson HS, Nolte H, Creticos P, et al. Efficacy and
safety of timothy grass allergy immunotherapy tablet
treatment in North America adults. J Allergy Clin Im-
munol. 2011;127:72–80.
34. Blaiss M, Maloney J, Nolte H, et al. Efficacy and safety
of timothy grass allergy immunotherapy tablet treat-
ment in North American children and adolescents. J
Allergy Clin Immunol. 2011;127:64–71.
35. Murphy K, Gawchik S, Bernstein D, et al. A phase 3
trial assessing the efficacy and safety of grass allergy
immunotherapy tablet in subjects with grass pollen-
induced allergic rhinitis with or without conjunctivi-
tis, with or without asthma. J Negat Results Biomed.
2013;12:10.
36. Bufe A, Eberle P, Franke-Beckmann E, et al. Safety and
efficacy in children of an SQ-standardized grass aller-
gen tablet for sublingual immunotherapy. J Allergy
Clin Immunol. 2009;123:167–173.e7.
37. Juniper EF, Thompson AK, Ferrie PJ, Roberts JN. Val-
idation of the standardized version of the Rhinocon-
junctivitis Quality of Life Questionnaire. J Allergy
Clin Immunol. 1999;104:364–369.
38. Petersen K, Gyrd-Hansen D, Kjaergarrd S, et al. Clin-
ical and patient based evaluation of immunother-
apy for grass pollen and mite allergy. Allergol Im-
munopathol (Madr). 2005;33:264–269.
39. Petersen KD, Kronborg C, Larsen JN, et al. Patient
related outcomes in a real life prospective follow up
study: allergen immunotherapy increases quality of
life and reduces sick days. World Allergy Organ J.
2013;6:15.
40. Han DH, Choi YS, Lee JE, et al. Clinical effi-
cacy of sublingual immunotherapy in pediatric pa-
tients with allergic rhinitis sensitized to house dust
mites: comparison to adult patients. Acta Otolaryn-
gol. 2012;132:S88-S93.
41. Lee JE, Choi YS, Kim MS, et al. Efficacy of sublin-
gual immunotherapy with house dust mite extract in
polyallergen sensitized patients with allergic rhinitis.
Ann Allergy Asthma Immunol. 2011;107:79–84.
42. Kiotseridis H, Cilio CM, Bjermer L, et al. Grass pollen
allergy in children and adolescents-symptoms, health
related quality of life and the value of pollen progno-
sis. Clin Transl Allergy. 2013;3:19.
43. Pfaar O, Kleine-Tebbe J, H ¨
ormann K, Klimek
L. Allergen-specific immunotherapy: which outcome
measures are useful in monitoring clinical trials? Im-
munol Allergy Clin North Am. 2011;31:289–309, x.
44. Esch RE, Bush RK. Aerobiology of outdoor allergens.
In: Adkinson NF, Bochner BS, Busse WW, et al., eds.
Middleton’s Allergy: Principles and Practice.7thed.
Philadelphia: Mosby Elsevier; 2003:510–512.
45. Cox L, Larenas-Linnemann D, Lockey RF, et al.
Speaking the same language: the World Allergy Or-
ganization subcutaneous immunotherapy systemic re-
action grading system. J Allergy Clin Immunol.
2010;125:569–574.
46. Erekosima N, Suarez-Cuervo C, Ramanthan M, et al.
Effectiveness of subcutaneous immunotherapy for al-
lergic rhinoconjunctivitis and asthma: a systemic re-
view. Laryngoscope. 2014;124:616–627.
47. Canonica GW, Baena-Cagnani CE, Bousquet J, et al.
Recommendations for standardization of clinical trials
with allergen specific immunotherapy for respiratory
allergy. A statement of a World Allergy Organization
(WAO) taskforce. Allergy. 2007;62:317–324.
48. Malling HJ. Immunotherapy as an effective tool in
allergy treatment. Allergy. 1998;53:461–472.
49. Calderon MA, Alves B, Jacobsen M, et al. Allergen in-
jection immunotherapy for seasonal allergic rhinitis.
Cochrane Database Syst Rev. 2007;1:CD001936.
50. Di Bona D, Plaia A, Leto-Barone SF, et al. Efficacy
of subcutaneous and sublingual immunotherapy with
grass allergens for seasonal allergic rhinitis: a meta-
analysis-based comparison. J Allergy Clin Immunol.
2012;130:1097–1107.
51. Balda BR, Wolf H, Baumgarten C, et al. Tree-
pollen allergy is efficiently treated by short-term
immunotherapy (STI) with seven preseasonal injec-
tions of molecular standardized allergens. Allergy.
1998;53:740–748.
52. Zenner HP, Baumgarten C, Rasp G, et al. Short term
immunotherapy: a prospective, randomized, double-
blind, placebo-controlled multicenter study of molec-
ular standardized grass and rye allergens in patients
International Forum of Allergy & Rhinology, Vol. 6, No. 2, February 2016 154
Efficacy of self-administered immunotherapy
with grass pollen-induced allergic rhinitis. J Allergy
Clin Immunol. 1997;100:23–29.
53. Drachenberg KJ, Wheeler AW, Stuebner P, Horak F.
A well-tolerated grass pollen specific allergy vaccine
containing a novel adjuvant, monophosphoryl lipid A,
reduces allergic symptoms after only four preseasonal
injections. Allergy. 2001;56:498–505.
54. Pastorello EA, Pravettoni V, Incorvaia C, et al. Clini-
cal and immunological effects of immunotherapy with
alum-absorbed grass allergoid in grass-pollen-induced
hay fever. Allergy. 1992;47:281–290.
55. Ortolani C, Pastorello EA, Incorvaia C, et al.
A double-blind, placebo-controlled study of im-
munotherapy with an alginate-conjugated extract of
Parietaria judaica in patients with Parietaria hay fever.
Allergy. 1994;49:13–21.
56. Jutel M, Jaeger L, Meyer H, et al. Allergen-specific im-
munotherapy with recombinant grass pollen allergens.
J Allergy Clin Immunol. 2005;116:608–613.
57. Ferrer M, Burches E, Pel ´
aez A, et al. Double-blind,
placebo-controlled study of immunotherapy with
Parietaria judaica: clinical efficacy and tolerance. JIn-
vestig Allergol Clin Immunol. 2005;15:283–292.
58. Corrigan CJ, Kettner J, Doemer C, et al. Efficacy and
safety of preseasonal-specific immunotherapy with an
aluminium-adsorbed six-grass pollen allergoid. Al-
lergy. 2005;60:801–807.
59. Col´
as C, Monz ´
on S, Venturini M, Lezaun A. Double-
blind, placebo-controlled study with a modified thera-
peutic vaccine of Salsola kali (Russian thistle) admin-
istered through use of a cluster schedule. J Allergy Clin
Immunol. 2006;117:810–816.
60. Creticos PS, Schroeder JT, Hamilton RG, et al. Im-
munotherapy with a ragweed-toll-like receptor 9 ag-
onist vaccine for allergic rhinitis. N Engl J Med.
2006;355:1445–1455.
61. Frew AJ, Powell RJ, Corrigan CJ, et al. Efficacy and
safety of specific immunotherapy with SQ allergen ex-
tract in treatment-resistant seasonal allergic rhinocon-
junctivitis. J Allergy Clin Immunol. 2006;117:319–
325.
62. Powell RJ, Frew AJ, Corrigan CJ, Durham SR. Effect
of grass pollen immunotherapy with Alutard SQ on
quality of life in seasonal allergic rhinoconjunctivitis.
Allergy. 2007;62:1335–1338.
63. Walker SM, Pajno GB, Lima MT, et al. Grass pollen
immunotherapy for seasonal rhinitis and asthma: a
randomized, controlled trial. J Allergy Clin Immunol.
2001;107:87–93.
64. Pfaar O, Robinson DS, Sager A, Emuzyte R. Im-
munotherapy with depigmented-polymerized mixed
tree pollen extract: a clinical trial and responder anal-
ysis. Allergy. 2010;65:1614–1621.
65. Davis WE, Cook PR, Mckinsey JP, et al. Anaphy-
laxis in immunotherapy. Otolaryng Head Neck Surg.
1992;107:78–83.
66. Tinkelman DG, Cole WQ 3rd, Tunno J. Immunother-
apy: a one-year prospective study to evaluate risk fac-
tors of systemic reactions. J Allergy Clin Immunol.
1995;95:8–14.
67. Iliopoulos O, Proud D, Atkinson F, et al. Effects of im-
munotherapy on the early, late, and rechallenge nasal
reaction to provocation with allergen: changes in in-
flammatory mediators and cells. J Allergy Clin Im-
munol. 1991;87:855–866.
68. Tworek D, Bochenska-Marciniak M, Kuprys-
Lipinska I, et al. Perennial is more effective than pre-
seasonal subcutaneous immunotherapy in the treat-
ment of seasonal allergic rhinoconjunctivitis. Am J
Rhinol Allergy. 2013;27:304–308.
69. Creticos PS, Marsh DG, Proud D, et al. Responses to
ragweed-pollen nasal challenge before and after im-
munotherapy. J Allergy Clin Immunol. 1989;84:197–
205.
70. Haugaard L, Dahl R, Jacobsen L. A controlled dose-
response study of immunotherapy with standardized,
partially purified extract of house dust mite: clini-
cal efficacy and side effects. J Allergy Clin Immunol.
1993;91:556–566.
71. Ewbank PA, Murray J, Sanders K, et al. A double-
blind, placebo-controlled immunotherapy does-
response study with standardized cat extract. J Allergy
Clin Immunol. 2003;111:155–161.
72. Lent A, Harbeck R, Strand M, et al. Immunological
response to administration of standardized dog aller-
gen extract at differing doses. J Allergy Clin Immunol.
2006;118:1249–1256.
73. Hassan E. Recall bias can be a threat to retrospec-
tive and prospective research designs. Internet J Epi-
demiol. 2005;3(2):1–6.
155 International Forum of Allergy & Rhinology, Vol. 6, No. 2, February 2016
