Subcutaneous and Sublingual

Immunotherapy To Treat Allergic

Rhinitis/Rhinoconjunctivitis and Asthma
Prepared for:
Agency for Healthcare Research and Quality (AHRQ)
www.ahrq.gov
Outline of Material
 Agency for Healthcare Research and Quality Comparative
Effectiveness Review (CER) Process
 Background
 Clinical Questions Addressed in the CER
 Summary of CER Results
 Conclusions
 Gaps in Knowledge
 Resources for Shared Decisionmaking
Agency for Healthcare Research and Quality (AHRQ)
Comparative Effectiveness Review (CER) Development
 Topics are nominated through a public process, which includes submissions
from health care professionals, professional organizations, the private
sector, policymakers, the public, and others.
 A systematic review of all relevant clinical studies is conducted by
independent researchers, funded by AHRQ, to synthesize the evidence in a
report summarizing what is known and not known about the select clinical
issue.
 The research questions and the results of the report are subject to expert
input, peer review, and public comment.
 The results of these reviews are summarized into a Clinician Research
Summary and a Consumer Research Summary for use in decisionmaking and
in discussions with patients.
 The Research Summaries and the full report are available at
www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.

Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111.
Available at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Rating the Strength of Evidence From the
Comparative Effectiveness Review
 The strength of evidence ratings are classified into four broad ratings:

AHRQ Methods Guide for Effectiveness and Comparative Effectiveness Reviews. Available at
http://www.effectivehealthcare.ahrq.gov/methodsguide.cfm.
Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Owens DK, Lohr KN, Atkins D, et al. J Clin Epidemiol. 2010 May;63(5):513-23. PMID: 19595577.
Background:
Allergic Rhinitis/Rhinoconjunctivitis and Asthma
 Allergic rhinitis is a common clinical problem affecting about 20
percent of the general population in North America.
 Allergens such as tree, grass, and weed pollens characteristically
cause seasonal rhinoconjunctivitis and/or asthma.
 Allergens such as cat dander, cockroach, or dust mite may induce
symptoms year-round and are associated with perennial rhinitis
and/or asthma.
 The prevalence of asthma in the general U.S. population is
approximately 9 percent, and approximately 62 percent of
individuals with asthma have evidence of atopy (i.e., the genetic
predisposition to produce elevated immunoglobulin E [IgE] in
response to environmental allergens).

Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available
at http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Min YG. Allergy Asthma Immunol Res. 2010 Apr;2(2):65-76. PMID: 20358020.
Background: Management of Allergy Symptoms
 The medical management of patients with allergic
rhinitis and allergic asthma includes:
 Allergen avoidance
 Pharmacotherapy
 Immunotherapy
 Daily use of pharmacotherapies for allergic asthma and
rhinitis symptoms raises issues related to adherence,
safety, and cost.
 Long-term use of inhaled steroids, long-acting
bronchodilators, and leukotriene antagonists for asthma
control can have adverse effects.
Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm
Background:
Subcutaneous Immunotherapy for Allergies
 Allergen-specific immunotherapy is typically used for:
 Patients whose allergic rhinoconjunctivitis and asthma symptoms
cannot be controlled by medication and environmental control
 Patients who cannot tolerate their medications
 Patients who do not comply with chronic medication regimens
 The U.S. Food and Drug Administration has approved the use
of allergen extracts for subcutaneous immunotherapy in
treating seasonal and perennial allergic rhinitis and allergic
asthma.
 In the United States, a patient with allergies undergoing
immunotherapy receives subcutaneous injections—in
increasing doses until a maintenance dose is found—of an
allergen-containing extract comprised of the relevant
allergens to which he or she is sensitive in an attempt to
suppress or eliminate allergy-related symptoms.
Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Background:
Sublingual Immunotherapy for Allergies
 There is considerable interest in using similar allergen extracts as
sublingual immunotherapy (SLIT) as an alternative to
subcutaneous immunotherapy.
 SLIT involves placing drops or tablets with the allergen extract
under the tongue for local absorption to desensitize the allergic
individual over a period of months to years and to diminish
allergic symptoms.
 In the United States, there currently are no sublingual forms of
immunotherapy approved by the U.S. Food and Drug
Administration.
 However, some U.S. physicians are using subcutaneous aqueous
extracts off-label for sublingual desensitization in the treatment
of allergic respiratory conditions.
Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Systematic Review: Objective and Key Questions
 Objective
 To evaluate the efficacy, effectiveness, and safety of
subcutaneous (SCIT) and sublingual (SLIT) immunotherapies
that are presently available for use by clinicians and patients
in the United States
 Key Questions
 For patients with allergic rhinoconjunctivitis and/or asthma:
 Efficacy and effectiveness of SCIT, SLIT, and SCIT versus SLIT
 Safety of SCIT, SLIT, and SCIT versus SLIT
 Safety and effectiveness of SCIT, SLIT, and SCIT versus SLIT in
the pediatric subpopulation

Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm
Outcomes of Interest
 Primary Outcomes  Adverse Effects
 Clinical endpoints:  Local reactions
 Symptom control  Skin, mouth, and throat (including
 Medication use irritation, itching, swelling, or
 Quality of life pain in the oral cavity)
 General symptoms (such as
 Disease evolution/remission
headache, fatigue, arthritis)
 New allergen sensitivities  Systemic reactions
 Overall health care utilization  Ocular
 Missed days of school/work  Rhinitis/nasal
 Secondary Outcomes  Cutaneous
 Functional tests (pulmonary  Rash
function test‒forced expiratory  Gastrointestinal
volume)
 Respiratory/asthma
 Provocational test
 Cardiovascular
 Adherence
 Anaphylaxis
 Convenience and compliance  Death
 Biomarkers
Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Overview of Studies Included in the
Systematic Review
 142 studies were included in the review with these populations: adults
only (52%), children only (24%), and adults and children (22%).
 Studies on SLIT mainly included patients with allergic rhinitis and/or mild
asthma.
 All included studies were randomized controlled trials.
 Efficacy and safety of SCIT: n = 74
 Efficacy and safety of SLIT*: n = 60
 Comparisons of SCIT versus SLIT: n = 8
 The types of scales/scoring systems used in the studies were not uniform.
 Followup varied and ranged from one pollen season to 6 years.
 Standard therapy varied across trials.
 Due to heterogeneity in reported outcomes, results often only reflect the
percentage of trials in which a significant effect was seen for the
immunotherapy arm versus controls and not the magnitude of effect.
*SLIT refers to allergen extracts that are administered sublingually in the form of drops. Studies on sublingual
tablets are not included here.
Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Included Studies by Type of Allergen for SCIT,
SLIT, and SCIT Versus SLIT
Allergen SCIT SLIT SCIT vs. SLIT
Dust mite 21 14 6
Grass 11 15 ‒
Weeds 9 7 ‒
Cat 5 2 ‒
Dog 1 ‒ ‒
Mold 6 2 ‒
Tree 6 13 2
Multiple allergens 15 7 ‒
SCIT = subcutaneous immunotherapy; SLIT = sublingual immunotherapy

Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Included Studies for Subcutaneous Immunotherapy
Versus Placebo or Standard Therapy
 74 articles were included with a total of 4,350 patients.
 The primary diagnoses were:
 Asthma in 19 studies
 Asthma with rhinitis in 18 studies
 Rhinoconjunctivitis in 14 studies
 Asthma with rhinoconjunctivitis in 14 studies
 Types of allergens evaluated:
 Seasonal allergens such as trees, grasses, weeds, and seasonal molds
in 59 percent of studies
 Perennial allergens in 38 percent of studies
 Seasonal and perennial allergens in 3 percent of studies
 The heterogeneity of the data on clinical outcomes precluded
pooling of the data for further analysis. Consequently, the results
often only reflect the percentage of trials in which a significant
effect was seen for the immunotherapy arm versus controls and not
the magnitude of effect.
Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Subcutaneous Immunotherapy Versus Placebo or
Standard Therapy: Asthma Outcomes
Primary No. of RCTs, Strength of
Outcome Results* No. of Patients (n) Evidence
Asthma 17‒84% greater
16 RCTs,
symptom score improvement vs. High
n = 1,178
controls
Use of asthma Decreased in
12 RCTs,
medications 42% of studies High
n = 1,062
vs. controls
Combined Significant
asthma symptom improvement in 6 RCTs,
Low
and medication 83% of studies n = 196
score vs. placebo
RCT = randomized controlled trial

Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
SCIT Versus Placebo or Standard Therapy:
Rhinitis/Rhinoconjunctivitis Outcomes (1 of 2)

No. of RCTs, Strength

Primary Outcome Results No. of Patients (n) of Evidence

Rhinitis/ Significant improvement

rhinoconjunctivitis in 73% of studies vs. 25 RCTs,
High
symptoms controls n = 1,734

Use of rhinitis/ Significantly decreased in

10 RCTs,
rhinoconjunctivitis 70% of studies vs. controls Moderate
n = 564
medications
Combined rhinitis/ Significant improvement
rhinoconjunctivitis in 83% of studies vs. 6 RCTs,
Low
symptom and controls n = 400
medication score
RCT = randomized controlled trial; SCIT = subcutaneous immunotherapy

Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
 SCIT Versus Placebo or Standard Therapy:
Rhinitis/Rhinoconjunctivitis Outcomes (2 of 2)
No. of RCTs, Strength
Primary Outcome Results No. of Patients (n) of Evidence
Conjunctivitis Significant
14 RCTs,
symptoms improvement in 43% of High
n = 1,104
studies vs. placebo
Combined symptoms Significant
(nasal, ocular, and improvement in 67% of 6 RCTs, High
bronchial) studies vs. placebo n = 591

Disease-specific quality Significant

of life in patients with improvement by RQLQ 6 RCTs,
High
rhinitis/ in 67% of studies vs. n = 889
rhinoconjunctivitis placebo
RCT = randomized controlled trial; RQLQ = Rhinoconjunctivitis Quality of Life Questionnaire;
SCIT = subcutaneous immunotherapy

Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
SCIT Versus Placebo or Standard Therapy:
Asthma Plus Rhinitis/Rhinoconjunctivitis Outcomes

No. of RCTs, Strength

Primary Outcome Results No. of Patients (n) of Evidence
Asthma plus rhinitis/ 21‒68% greater
rhinoconjunctivitis 5 RCTs,
improvement vs. Moderate
symptoms n = 175
controls
Use of asthma plus • 14–83% greater
rhinoconjunctivitis reduction in asthma- 5 RCTs,
medications based studies vs. n = 203
controls
• Significantly High
decreased in 91% of 11 RCTs,
rhinitis-based n = 768
studies vs. controls
RCT = randomized controlled trial; SCIT = subcutaneous immunotherapy

Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Included Studies for Sublingual Immunotherapy
Versus Placebo or Standard Therapy
 60 articles on sublingual immunotherapy (SLIT) that included 4,870 patients were
eligible for inclusion.
 Allergens evaluated included:
 Seasonal allergens (66%)
 Perennial allergens (31%)
 Both seasonal and perennial allergens (3%)
 Comparators included:
 Placebo (71%)
 Another sublingual intervention without a placebo group (15%)
 Conventional treatment without placebo (pharmacotherapy or rescue medications;
14%)
 Duration of treatment ranged from 3 months to 5 years.
 There was great heterogeneity in:
 Dosages of maintenance or cumulative treatments
 The units to report dosing
 Standard therapy used across trials
 Reported results often only reflect the percentage of trials in which a significant
effect was seen for the immunotherapy arm versus controls and not the
magnitude of effect.
Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Sublingual Immunotherapy Versus Placebo or
Standard Therapy: Asthma Outcomes

No. of RCTs, Strength of

Primary Outcome Results No. of Patients (n) Evidence
Asthma symptom Significant
score improvement 13 RCTs,
High
across all studies n = 625
vs. controls
RCT = randomized controlled trial

Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
SLIT Versus Placebo or Standard Therapy:
Rhinitis/Rhinoconjunctivitis Outcomes
No. of RCTs, Strength
Primary Outcome Results No. of Patients (n) of Evidence
Rhinitis/ Significant improvement
36 RCTs,
rhinoconjunctivitis in 56% of studies vs. Moderate
n = 2,658
symptoms controls
Conjunctivitis Significant improvement
13 RCTs,
symptoms in 46% of studies vs. Moderate
n = 1,074
placebo
Disease-specific Significant improvement
quality of life in patients by RQLQ in 75% of 8 RCTs,
Moderate
with rhinitis/ studies vs. controls n = 819
rhinoconjunctivitis

RCT = randomized controlled trial; RQLQ = Rhinoconjunctivitis Quality of Life Questionnaire

Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
SLIT Versus Placebo or Standard Therapy:
Asthma Plus Rhinitis/Rhinoconjunctivitis Outcomes
No. of RCTs, Strength
Primary Outcome Results No. of Patients (n) of Evidence
Asthma plus rhinitis/ Significantly
rhinoconjunctivitis improved in 80% 5 RCTs,
Moderate
symptoms of studies vs. n = 308
controls
Use of asthma plus Significant
rhinoconjunctivitis improvement in 38 RCTs,
Moderate
medications 47% of studies vs. n = 2,724
controls
Asthma plus rhinitis/ Significant
rhinoconjunctivitis improvement in 19 RCTs,
Moderate
symptom and medication 68% of studies vs. n = 1,462
score controls
RCT = randomized controlled trial

Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
 Subcutaneous Versus Sublingual Immunotherapy:
All Outcomes
No. of RCTs, Strength of
Primary Outcome Results No. of Patients (n) Evidence
Improves asthma symptom SCIT may improve asthma
4 RCTs,
score symptoms more effectively Low
n = 171
than SLIT
Improves rhinitis/ SCIT is superior to SLIT
6 RCTs,
rhinoconjunctivitis for improving allergic Moderate
n = 412
symptoms nasal and/or eye symptoms
Decreases use of asthma There are no consistent
5 RCTs,
plus rhinoconjunctivitis differences between SCIT Low
n = 219
medications and SLIT
Improves asthma plus SCIT is favored in 1 of 2
rhinitis/rhinoconjunctivitis studies 2 RCTs,
Low
symptom and medication n = 65
score
RCT = randomized controlled trial; SCIT = subcutaneous immunotherapy; SLIT = sublingual
immunotherapy
Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Included Studies for SCIT Versus Placebo or
Standard Therapy in the Pediatric Population
 Thirteen studies on subcutaneous immunotherapy included 920
pediatric patients.
 The pediatric population ranged in age from 3 to 18 years.
 Primary diagnoses included:
 Asthma in 7 studies
 Asthma with rhinitis in 3 studies
 Asthma with rhinoconjunctivitis in 2 studies
 Rhinoconjunctivitis in 1 study
 All studies allowed either conventional pharmacotherapy or
rescue allergy medications during the study.
 Standard therapy varied across studies.
 Due to heterogeneity in reported clinical outcomes, results often
only reflect the percentage of trials in which a significant effect
was seen for the immunotherapy arm versus controls and not the
magnitude of effect.
Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Pediatric Patients—SCIT Versus Placebo or
Standard Therapy: Asthma Outcomes

Primary No. of RCTs, Strength of

Outcome Results No. of Patients (n) Evidence
Asthma Significant
symptom score improvement in 6 RCTs,
Moderate
50% of studies n = 550
vs. controls
Use of asthma Significant
4 RCTs,
medications reduction in 50% Low
n = 470
of studies
RCT = randomized controlled trial; SCIT = subcutaneous immunotherapy

Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Pediatric Patients—SCIT Versus Placebo or Standard
Therapy: Rhinitis/Rhinoconjunctivitis Outcomes
No. of RCTs, Strength of
Primary Outcome Results No. of Patients (n) Evidence
Rhinitis/ Significant
rhinoconjunctivitis improvement in 67% 3 RCTs, Moderate
symptoms of studies vs. placebo n = 285
Conjunctivitis Significant
symptoms improvement in 67% 3 RCTs, Low
of studies vs. placebo n = 285
Disease-specific Significant
quality of life in improvement in both
patients with studies vs. controls 2 RCTs,
Low
rhinitis/ n = 350
rhinoconjunctivitis

RCT = randomized controlled trial ; SCIT = subcutaneous immunotherapy

Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Pediatric Patients—SCIT Versus Placebo or Standard
Therapy: Asthma Plus Rhinitis/Rhinoconjunctivitis Outcomes

No. of RCTs, Strength

Primary Outcome Results No. of Patients (n) of Evidence
Use of asthma plus Decreased in
rhinoconjunctivitis both studies vs. 2 RCTs,
Low
medications controls n = 80

Improves combined Significant

asthma or asthma improvement in
plus rhinitis/ both studies vs. 2 RCTs,
Low
rhinoconjunctivitis placebo n = 85
symptom and
medication score
RCT = randomized controlled trial; SCIT = subcutaneous immunotherapy

Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Included Studies for SLIT Versus Placebo or
Standard Therapy in the Pediatric Population
 18 studies including 1,583 pediatric patients (≤ 18 years of age)
 Primary diagnoses:
 Asthma (n = 3 studies)
 Rhinitis (n = 2 studies)
 Rhinoconjunctivitis (n = 4 studies)
 Asthma and rhinitis (n = 4 studies)
 Asthma with rhinoconjunctivitis (n = 5 studies)
 Perennial and/or seasonal allergies were included
 Comparator groups included:
 Placebo (n = 15 studies)
 Sublingual immunotherapy (SLIT) comparator group (n = 3 studies)
 Pharmacotherapy/symptomatic therapy (n = 2 studies)
 Due to heterogeneity in reported clinical outcomes, results often only
reflect the percentage of trials in which a significant effect was seen for
the immunotherapy arm versus controls and not the magnitude of
effect.
Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Pediatric Patients—SLIT Versus Placebo or
Standard Therapy: Asthma Outcomes

Primary No. of RCTs, Strength of

Outcome Results No. of Patients (n) Evidence
Asthma Significant
symptom score improvement 9 RCTs,
in all studies High
n = 471
vs. controls
RCT = randomized controlled trial; SLIT = sublingual immunotherapy

Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Pediatric Patients—SLIT Versus Placebo or Standard
Therapy: Rhinitis/Rhinoconjunctivitis Outcomes

No. of RCTs, Strength of

Primary Outcome Results No. of Patients (n) Evidence
Rhinitis/ Significant
rhinoconjunctivitis improvement in 12 RCTs,
symptoms 42% of studies vs. n = 1,065 Moderate
controls
Conjunctivitis Significant
symptoms improvement in 5 RCTs,
40% of studies vs. n = 513 Moderate
placebo

RCT = randomized controlled trial; SLIT = sublingual immunotherapy

Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Pediatric Patients—SLIT Versus Placebo or Standard
Therapy: Asthma Plus Rhinitis/Rhinoconjunctivitis Outcomes

No. of RCTs, Strength

Primary Outcome Results No. of Patients (n) of Evidence

Asthma plus rhinitis/ Significant

rhinoconjunctivitis improvement with 1 RCT,
symptoms Moderate
high- and low-dose n = 98
SLIT vs. placebo
Use of asthma plus Significantly
rhinoconjunctivitis 13 RCTs,
reduced in 42% of Moderate
medications n = 1,078
studies vs. controls
Asthma plus rhinitis/ Significant
rhinoconjunctivitis improvement in 50% 2 RCTs,
symptom and Low
of studies vs. n = 329
medication score controls

RCT = randomized controlled trial; SLIT = sublingual immunotherapy

Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
 Pediatric Patients—SCIT Versus SLIT:
All Outcomes
No. of RCTs, Strength of
Primary Outcome Results No. of Patients (n) Evidence

Improves asthma SCIT is favored in 67% 3 RCTs,

Low
symptom score of studies vs. SLIT n = 135
Improves asthma plus SCIT may be favored
rhinitis/ over SLIT for reducing 3 RCTs,
rhinoconjunctivitis nasal and/or eye Low
n = 135
symptoms symptoms
Decreases use of asthma SLIT may decrease
plus rhinoconjunctivitis medication use more 3 RCTs,
Low
medications than SCIT, but results n = 135
are inconsistent
RCT = randomized controlled trial; SCIT = subcutaneous immunotherapy; SLIT = sublingual
immunotherapy

Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Adverse Effects:
Subcutaneous Immunotherapy in Adults
 Local reactions (such as redness, swelling, pruritus, or
induration at the injection site) were usually mild and
occurred in 5 to 58 percent of patients and 0.6 to 54 percent
of injections and were more common than systemic reactions.
 The most common systemic reactions were respiratory
reactions, occurring in up to 46 percent of patients and in up
to 3 percent of injections.
 General symptoms (such as headache, fatigue, and arthritis)
occurred in up to 44 percent of patients and were usually mild
or unspecified.
 Gastrointestinal reactions were reported in only one study.
 Thirteen anaphylactic reactions were reported in four trials.
 No deaths were reported in the included studies.
Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Adverse Effects:
Sublingual Immunotherapy in Adults
 Local reactions (such as irritation, itching, swelling, or pain
in the oral cavity) were common and usually mild and
occurred in 0.2 to 97 percent of patients receiving
sublingual immunotherapy (SLIT).
 Systemic reactions occurred more frequently in the SLIT
arm versus controls and included ocular, rhinitis/nasal,
respiratory/asthma, cutaneous, gastrointestinal, and
cardiovascular adverse effects.
 No life-threatening reactions, anaphylaxis, or deaths were
reported in the included trials.
 SLIT studies mainly include patients with allergic rhinitis
and/or mild asthma. Safety outcomes should not be
extrapolated to more severely affected patients.
Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Adverse Effects: Subcutaneous Versus Sublingual
Immunotherapy in Adults
 The recording and reporting of the adverse events was
neither uniform nor comparable across studies.
 Local reactions were common and were all of mild or
moderate severity.
 There was one report of anaphylaxis with subcutaneous
immunotherapy.
 There were no reported deaths in the included studies.

Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Adverse Effects: Subcutaneous Immunotherapy
in Pediatric Patients
 Local reactions were the most common adverse reactions
in the pediatric population receiving subcutaneous
immunotherapy.
 There were no reports of anaphylaxis or deaths.

Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Adverse Effects: Sublingual Immunotherapy in
Pediatric Patients
 Local reactions (such as irritation, itching, swelling, or
pain in the oral cavity) were common but mild.
 No life-threatening reactions, anaphylaxis, or deaths
were reported in these trials.
 The strength of evidence for all other adverse effects is
insufficient.

Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Adverse Effects: Subcutaneous Versus Sublingual
Immunotherapy in Pediatric Patients
 Local reactions were reported in both patient groups.
 No systemic reactions were reported in patients
receiving sublingual immunotherapy.
 In the pediatric population taking subcutaneous
immunotherapy, one anaphylaxis event and three
respiratory systemic reactions were reported.

Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Overview of Conclusions (1 of 2)
 There is sufficient evidence to support the overall
effectiveness and safety of both subcutaneous
immunotherapy (SCIT) and sublingual immunotherapy
(SLIT) for treating allergic rhinoconjunctivitis and
asthma.
 However, there is not enough evidence to determine if
either SCIT or SLIT is superior.
 SCIT and SLIT are usually safe, although local reactions
are commonly reported regardless of the mode of
delivery.

Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Overview of Conclusions (2 of 2)
 Serious, life-threatening reactions are rare, although they can
occur.
 Studies of sublingual immunotherapy (SLIT) mainly include
patients with allergic rhinitis and/or mild asthma.
 Safety outcomes should not be extrapolated to more severely
affected patients.
 Most of the studies in the review used a single allergen for
immunotherapy, and it may be difficult to extrapolate these
results to the use of multiple-allergen regimens, which are
commonly used in clinical practice in the United States.
 Due to the wide variety of reported regimens, the target SLIT
maintenance dose and duration of therapy are unclear.

Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Gaps in Knowledge
 Additional studies are needed on:
 The efficacy and safety of multiple-allergen subcutaneous (SCIT) and
sublingual (SLIT) immunotherapy
 The effectiveness of single-allergen versus multiple-allergen SCIT
and SLIT for desensitization
 The efficacy and safety of SCIT and SLIT in specific subpopulations
(pregnant women, monosensitized vs. polysensitized patients,
patients with severe asthma, and urban vs. rural patients)
 Whether or not SCIT and SLIT can prevent or modify the atopic
march in pediatric patients at high risk for allergic rhinitis and
asthma, as well as the optimal age to initiate therapy
 Determining the target maintenance dose, dosing strategies, and the
necessary durations of treatment for SCIT and SLIT
 Direct comparisons of SCIT to SLIT in pediatric and adult patients
 Optimizing allergen standardization for subcutaneous and sublingual
regimens

Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Shared Decisionmaking:
What To Discuss With Your Patients
 The benefits and adverse effects of subcutaneous (SCIT) or
sublingual (SLIT) immunotherapy for them or their child
 Any comorbid conditions that they or their child may have
that would affect their ability to take SCIT or SLIT
 Other prescription or over-the-counter medications they
are taking during SCIT or SLIT treatment
 What adverse effects to look for and when to call their
doctor
 How often they should be taking SCIT or SLIT
 How long they can expect to take SCIT or SLIT
 The costs of SCIT and SLIT
Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.
Resource for Patients
 Allergy Shots and Allergy Drops
for Adults and Children, A Review
of the Research is a free resource
that can help patients talk with
their health care professionals
about treatment options.
It provides information about:
 Allergies in general
 How allergies are treated
 Allergy shots and allergy drops
 The benefits of allergy shots and
allergy drops for adults and
children
 Possible side effects of allergy
shots and allergy drops for adults
and children
 Questions to discuss with their
doctor
 Lin SY, Erekosima N, Suarez-Cuervo C, et al. AHRQ Comparative Effectiveness Review No. 111. Available at
http://www.effectivehealthcare.ahrq.gov/allergy-asthma-immunotherapy.cfm.