1. Immunotherapy SCIT/SLIT
John Oppenheimer MD
Rutgers Univ. School of Med

2. Learning Objectives The participant will be able to:
use current guidelines to improve the safety and effectiveness of SCIT and SLIT

3. Potential Conflicts Consultant/Clinical Research:
AZ/BI/Glaxo/Merck/Novartis/Genetech/Meda
Associate Editor: Annals of Allergy, Allergy Watch, Current Allergy and Asthma Reports
Board of Directors: ABAI

4. Practice Parameters for IT
Initially published in Ann Allergy 2003;90(1)
Defined extracts as diagnostic
Defined “maintence concentrate” as a vaccine
Estimated effective doses
Standardized labeling
Second Update in JACI. 2007; 120(3)
Instead of vaccines now called immunotherapy extracts
Effective doses further defined
Cross-reactivity patterns refined
Compatibility refined
Patient vials rather than off the board
Standardized forms for skin testing, IT prescriptions and delivery

5. Practice Parameters for IT Third update
Update published in 2011
New requirements for extract preparation
USP 797
New indications for immunotherapy
Further defined responses to reactions to immunotherapy
Medications and immunotherapy reviewed
Expanded discussion of SLIT

6. General Rule for Success
Ideally use patient-specific vials
Individualized to each patient with identifiers
Avoid
Multi-patient vials
Off the board
Include an effective dose of each component
Avoid inclusion of cross-reacting antigens
Avoid mixing incompatible extracts
protease
Esch JACI 2008;122:

7. It works!

8. 18
ANTIGEN E
Placebo
Aqueous Extract
Pollen Count
3500 16
3000 14
2500 12 10
2000
Symptom Index
Pollen Count 8
1500 6
1000 4
500 2 15 20 25 30 1 4 5 14 19 24 29
AUGUST
SEPTEMBER
1964
Norman J. A. 1968;42:93

9. 3833 16 14 12 10 8 6 4 2
3000
2500
2000
1500
1000
500
AUGUST
SEPTEMBER
1965
Symptom Index
Pollen Count
OCTOBER 18 22 26 30 1 20 24 28
ANTIGEN E
Placebo
Aqueous Extract
Pollen Count

10. Journal of Allergy and Clinical Immunology5
SYMPTOM INDEX 15 14 12 10 8 6 4 2
500
1000
1500
2000
2500
3000
AUGUST
SEPTEMBER
OCTOBER
POLLEN COUNT
1967
Antigen E
Placebo
Aqueous Extract
Pollen Count 15 20 25 30 1 5 10 15 20 25 30 8

11. 16 14
ANTIGEN E
Placebo
Aqueous Extract
Pollen Count
2500 12 10
2000 8
Symptom Index
1500 6
Pollen Count
1000 4 2
500 16 20 24 28 2 6 10 14 18 22 26 30 4 8
AUGUST
SEPTEMBER
OCTOBER
Norman JACI 1971;47:273
1968

12. Usefulness of Immunotherapy in Patients with Severe Summer Hay Fever Uncontrolled by Anti-allergic Drugs
40 adults with severe grass pollen allergy uncontrolled by standard anti-allergic drugs.
Two month immunotherapy build-up during April and May, then monthly maintenance.
Alum adsorbed extract
Varney VA, Gaga M, Frew AJ, Aber VR, Kay AB, Durham SR. BMJ 1991;302:265

13. Reduction in Rhinitis Symptoms and Medication Use from Immunotherapy
100
Grass Pollen Count 80
Symptoms
150
Drugs
IT Treatment
IT Treatment 70
Placebo 80
120
Placebo 60
Counts/m 60 50
Median Score 90
Median Score 40 40 60 30 20 20 30 10 24
April
May
June
July
August
September
Varney et al. BMJ. 1991;302:

14. Immunotherapy (immunomodulatory)
Immunoglobulins
Specific IgE decreases
Specific IgG increases
Cells
TH2 to TH1 phenotype switch
Mediators
IL4 and IL-5 to IL-2 and IFN gamma
Local changes
Target organ reactivity decreases

15. Intracellular Expression of IL-10 by CD4+CD25+ Lymphocytes After Immunotherapy
PBMCs from IT patients stimulated with P. pratense
CD4+CD25+ expression by allergen-stimulated cells
Francis JN, et al. J. Allergy Clin. Immunol. 2003;111:

16. Pick the correct dose!

17. AJ Frew et al. J Allergy Clin Immunol 2006;117:319-25
Efficacy and Safety of Specific Immunotherapy with SQ Allergen Extract in Treatment-resistant Seasonal allergic Rhinoconjunctivitis
347 adults with grass-pollen induced SAR inadequately controlled in previous year by antihistamines, topical steroids and eye drops
Randomized to pre-seasonal immunotherapy with timothy grass extract high dose (20 mcg Phl p 5), low dose (2 mcg Phl p 5) or placebo
AJ Frew et al. J Allergy Clin Immunol 2006;117:319-25

18. Efficacy and Safety of Specific Immunotherapy with SQ Allergen Extract in Treatment-resistant Seasonal allergic Rhinoconjunctivitis (Results compared to placebo during peak pollen period)
Symptoms Medication High-dose timothy - 32% (p < .0001) - 41% (p < .0001) Low-dose timothy - 19% (p = .014) - 14% (p = .16 NS)
Systemic reactions Early (urt or asthma) late (urt, AE, or asthma) (< 1 hour) (1-24 hours) High-dose timothy 9 (4.4%) 39 (16%) Low-dose timothy (4%) Placebo (2%)
AJ Frew et al. J Allergy Clin Immunol 2006;117:319-25

19. AJ Frew et al. J Allergy Clin Immunol 2006;117:319-25

20. AJ Frew et al. J Allergy Clin Immunol 2006;117:319-25

21. Potency of currently available manufacturer’s extracts
Extract Potency
Cat hair and pelt and 10,000 BAU/mL
Dust mite 3000, 5000, 10,000, and 30,000 AU/mL
Bermuda grass 10,000 AU/mL
Short ragweed 1:10-1:20 wt/vol or 100,000 AU/mL
Other grasses* 10,000 and 100,000 BAU/mL
Other pollen 1:10 to 1:40 (wt/vol) or 10,000 PNU/mL
Molds 1:10 to 1:40 (wt/vol) or 20,000 to 100,000 PNU/mL
AU, Allergy unit; BAU, bioequivalent allergy unit; PNU, protein nitrogen unit.
*Perennial rye, Kentucky blue/June, timothy, sweet vernal, redtop, orchard, and meadow.

22. Probable effective dose range for allergen extracts: US units
Antigen Labeled potency or concentration Probable effective dose range
Dust mites: (D farinae and D pteronyssinus) 3000, 5000, 10,000, and 30,000 AU/mL AU
Cat ,000 BAU/mL BAU
Grass, standardized 10, ,000 BAU/mL BAU
Short ragweed 1:10 to 1:20 wt/vol 100,000 AU/mL mg of Amb a 1
(Concentration of Amb a 1 is on the label of wt/vol extracts) AU
Nonstandardized extracts
Dog 1:10 to 1:100 wt/vol 15 mcg of Can f 1
Other extracts 1:10 to 1:40 wt/vol or 2.5 to 10mg
10,000-40,000 PNU/mL Highest tolerated dose 22

23. Median Dosing Recommendations by Board Certified Allergists for Immunotherapy
Allergen Mean % Effective Timothy 18.6 mcg mcg 15.0 mcg Ragweed 26.8 mcg mcg 12.0 mcg Dp mcg mcg mcg Df mcg mcg 10.0 mcg Cat 1.6 mcg mcg 11.0 mcg
Nelson, HS. JACI 2000;106:41

24. Prolonged protection!

25. Subcutaneous Immunotherapy: Effect on Serum Specific IgE
Initiation of
immunotherapy 70 60
August 50
November
Anti - ragweed
IgE
(ng/ml) 40 30 20 10
baseline
year 1
year 2
year 6
year 7
year 8
Peng et al. J Allergy Clin Immunol 1992;89:519

26. Long-Term Clinical Efficacy of Grass-Pollen Immunotherapy
Methods:
Randomized, double-blind, placebo-controlled trial of the discontinuation of immunotherapy for grass-pollen allergy in patients in whom three to four years of this treatment had previously been shown to be effective.
921 continued immunotherapy
504 discontinued immunotherapy
During the three years of this trial, primary outcome measures were scores for seasonal symptoms and the use of rescue medication.
Objective measures included the immediate conjunctival response and the immediate and late skin responses to allergen challenge.
A matched group of patients with hay fever who had not received immunotherapy was followed as a control for the natural course of the disease.
Durham et al. N Eng J Med 1999;341:468

27. Long-Term Efficacy of Subcutaneous Immunotherapy80
Immunotherapy continued 60 40 20
May
June
July
Aug.
1993
Symptom score
1994
1995
Placebo
Immunotherapy 80 60 40 20
May
June
July
Aug.
Symptom score
1989
Immunotherapy discontinued
Durham et al. N Eng J Med 1999;341:468

28. Long-term benefits of SCIT
6-yr follow-up study of grass pollen IT
Symptoms and medication use remained lower in the SCIT group
23% in active IT v. 70% in control group experienced asthma sxs
Skin test reactivity remained lower
61% in active IT v. 100% in control developed new sensitizations
6-yr follow-up of tree pollen IT
Sxs remained improved at “the same level” in 86% of AR patients
Skin test reactivity remained unchanged as at the end of IT
Specific IgE remained at the same level as at the end of IT
Jacobsen L et al. Allergy 1997; 52:
Eng PA et al. Allergy 2012;57:306-12

29. Break Even Point For Cost Effectiveness of SCIT v
Break Even Point For Cost Effectiveness of SCIT v. Nasal Corticosteroids
Design:
To determine the timing at which initiation of specific IT becomes more cost-effective than continued nasal steroid therapy in the treatment of allergic rhinitis using a decision- making model.
Results:
For patients with seasonal allergic rhinitis requiring NS 3 months and 4 months per year, the age at which initiation of IT provides long- term direct cost advantage is less than 41 years and 50 years, respectively.
For patients with perennial rhinitis symptoms requiring year-round NS, the cut-off age for IT raises to 65 years.
*Kennedy, J, L Borish, D Robinson, J Christophel, and S Payne S Annals of Allergy, Asthma & Immunology 2011;107:A35.

30. Could IT Prevent New Sensitization or Prevent Asthma?

31. Prevention of New Sensitizations in Asthmatic Children Monosenstized to HDM by Specific IT. A Six year F/U
Methods
134 children (5-8 yo) with intermittent asthma +/- AR monosensitized to HDM
Parents of 75 children accepted IT
Parents of 63 declined IT
IT x 3yrs with f/u for 3 further yrs
Maintenance dose was ½ usual adult dose
Pajno GB Clin Exp All 2001;31:1392-7

32. Prevention of New Sensitizations in Asthmatic Children Monosenstized to HDM by Specific IT. A Six year F/U
Results
At the end of 6 yrs, new sensitizations occurred in:
IT 17/69 (24.5%)
No IT 36/54 (66.7%)
Pajno GB Clin Exp All 2001;31:1392-7

33. Back to our rules for Success

34. Significant Cross-Allergenicity Among Trees
Birch family: birch, elder, hazelnut, hornbeam
Olive family: European olive, ash, privet, Russian olive (botanically unrelated)
Conifer family: cedar, cypress, juniper, arbor vitae.
Fagaceae family: beech, oak
Carya genus: pecan, hickory
Populus genus: poplar, cottonwood, aspen Use major local species for each group

35. Botonical Relationships Among the Grasses
Festucoideae: Northern pasture grasses
(timothy, orchard, June, red top, rye, etc)
Eragrostoideae: Bermuda, grama, and several Western prairie grasses.
Pancoideae: Bahia and Johnson grass Use timothy +/- other NPGs (but reduce amount of each. Use Bermuda/Bahia/Johnson if locally important

36. Botanical Relationships Among the Weeds
AMBROSIA: ragweeds,cocklebur, burweed marsh elder
ARTEMESIA: sages, wormwood, mugworts
AMARANTHS: pigweed, western water hemp, Palmer’s amaranth
Use locally important species
CHENOPHODS: Russian thistle, kochia, lambs quarters, atriplex species Treat both RT and Kochia if locally important

37. Protease Content of Various Extracts
Trypsin Equivalent Pollens < 1 g Cat & dog dander < 1g House dust mites (US) < 5 g Alternaria alternata 29 g American cockroach 168 g Aspergillus fumigatus 212 g Penicillium notatum 242 g
Robert Esch PhD, Greer Laboratories

38. Fig 1. Combinations producing low (X), moderate or risky (Ø), and favorable (+) compatibilities when allergenic extracts are mixed with protease-containing insect, fungal, and mite extracts are shown.
Esch JACI 2008;122: 38

39. IT and Asthma Cochrane Analysis 75 trials involving 3,506 subjects
3188 with asthma
Conclusions:
IT:
significantly reduces SX
significantly reduces Rx required
No consistent effect on lung function
Less likely to develop BHR
Modest improvement in nonspecific BHR
Significantly reduces allergen specific BHR
Abramson MJ Cochrane Database 2006

40. Allergen IT versus placebo, Asthma symptom scores
Abramson MJ Cochrane Database 2006

41. Injection allergen immunotherapy for asthma.
Objectives
The objective of this review was to assess the effects of allergen specific immunotherapy for asthma.
Search methods
The authors searched the Cochrane Airways Group Trials Register up to 2005, Dissertation Abstracts and Current Contents.
Selection criteria
Randomized controlled trials using various forms of allergen specific immunotherapy to treat asthma and reporting at least one clinical outcome.
Data collection and analysis
Three authors independently assessed eligibility of studies for inclusion.
Two authors independently performed quality assessment of studies.
Abramson Cochrane Database of Systematic Reviews
2010, Issue 8. Art. No.: CD

42. Injection allergen immunotherapy for asthma.
Main results
Eighty-eight trials were included.
There were
42 trials of immunotherapy for house mite allergy;
27 pollen allergy trials;
10 animal dander allergy trials;
two Cladosporium mold allergy,
two latex
six trials looking at multiple allergens.
Concealment of allocation was assessed as clearly adequate in only 16 of these trials.
Significant heterogeneity was present in a number of comparisons.
Abramson Cochrane Database of Systematic Reviews
2010, Issue 8. Art. No.: CD

43. Injection allergen immunotherapy for asthma.
Main results
Overall, there was a significant reduction in asthma symptoms and medication, and improvement in bronchial hyper-reactivity following immunotherapy.
There was a significant improvement in asthma symptom scores (standardized mean difference -0.59, 95% confidence interval to -0.35) and it would have been necessary to treat three patients (95% CI 3 to 5) with immunotherapy to avoid one deterioration in asthma symptoms.
Allergen immunotherapy significantly reduced allergen specific BHR, with some reduction in non-specific BHR as well.
There was no consistent effect on lung function.
If 16 patients were treated with immunotherapy, one would be expected to develop a local adverse reaction.
If nine patients were treated with immunotherapy, one would be expected to develop a systemic reaction (of any severity).
Abramson Cochrane Database of Systematic Reviews
2010, Issue 8. Art. No.: CD

44. Injection allergen immunotherapy for asthma.
Authors’ conclusions
Immunotherapy reduces asthma symptoms and use of asthma medications and improves bronchial hyper-reactivity.
One trial found that the size of the benefit is possibly comparable to inhaled steroids.
The possibility of local or systemic adverse effects (such as anaphylaxis) must be considered.
Abramson Cochrane Database of Systematic Reviews
2010, Issue 8. Art. No.: CD

45. Safety of Immunotherapy
Fatalities occur at a rate of 1 per 2.5 million injections (3.4/yr in the US/Canada)
Vast majority occur in asthmatics
Fatalities associated with:
Poorly controlled asthma
Delayed administration of epinephrine / resuscitation efforts
SCIT must be administered in a setting where prompt recognition and treatment of anaphylaxis is assured
Epi cc 1:1000 IM
Patients must remain in the physician’s office at least 20 mins (AR) - 30 mins (asthmatics) after an injection
Bernstein DI et al. J Allergy Clin Immunol 2004;113:

46. SLIT

47. SLIT Approved Doses PI Oralair
ORALAIR® (Sweet Vernal, Orchard, Perennial Rye, Timothy, and Kentucky BlueGrass Mixed Pollens Allergen Extract)
PI Oralair

48. SLIT Approved Doses
Grastek=Timothy grass 2800BAUs SL tablet yrs 1 Tab QD
Ragwitek=Short RW 12 Amb a 1 unit SL tab yrs 1 Tab QD
Medical Letter 2014;56:47

49. Clinical efficacy of 300IR 5-grass pollen sublingual tablet in a US study: The importance of allergen-specific serum IgE
Objectives:
We sought to evaluate the efficacy and safety of 300 index of reactivity (IR) 5- grass pollen sublingual tablet in US adults.
Methods:
Adults with grass pollen allergy and Rhinoconjunctivitis Total Symptom Scores of 12 or greater(scale,0-18) during the previous grass pollen season were randomized in a double-blind, placebo-controlled study to receive 300IR 5- grass pollen sublingual tablet or placebo starting 4 months before and continuing through the pollen season.
The primary efficacy end point was the daily Combined Score (CS; scale, 0-3), which integrates symptoms and rescue medication use.
Cox JACI 2012;130:

50. Clinical efficacy of 300IR 5-grass pollen sublingual tablet in a US study: The importance of allergen-specific serum IgE
Results:
Four hundred seventy-three participants were randomized.
The mean daily CS over the pollen period was significantly lower in the active treatment group versus the placebo group (least-squares mean difference: ; 95% CI, to -0.06; P=.0003; relative reduction: 28.2%; 95% CI, 13.0% to 43.4%).
In placebo-treated participants, the daily CS least-squares mean was 0.32 in the subgroup with baseline timothy grass–specific serum IgE of less than 0.1 kU/L (n=23) and 0.46 in those with baseline timothy grass–specific serum IgE of 0.1 kU/L or greater (n=204).
The most frequent reported adverse events were oral pruritus, throat irritation, and nasopharyngitis.
There were no reports of anaphylaxis, and no actively treated participant received epinephrine
Cox JACI 2012;130:

51. Fig 3. Mean daily CS and pollen count
Overall Δ P=0.0003
Cox JACI 2012;130:

52. FIG 4. RQLQ scores: change from baseline to the expected middle of the grass pollen period (FAS). Vertical bars are 95% CIs.
Overall P=.0042
Cox JACI 2012;130:

53. Randomized controlled trial of ragweed allergy immunotherapy tablet efficacy and safety in North American adults
Methods
Adults with ragweed pollen–induced AR/C were randomized 1:1:1 to daily ragweed AIT (6 or 12 Amb a 1 units) or placebo before, throughout, and after ragweed season
Patients could use predefined allergy rescue medications in season.
Efficacy end points included peak and entire season total combined score (TCS) and its components daily symptom score (DSS), and daily medication score (DMS).
Safety assessments included adverse events.

54. Randomized controlled trial of ragweed allergy immunotherapy tablet efficacy and safety in North American adults
Results
A total of 565 patients were randomized.
During peak season, the 6– and 12–Amb a 1 unit ragweed AIT doses showed 21% (−1.76 score) and 27% (−2.24 score) improvement in TCS vs placebo ( P < .05).
The 6– and 12–Amb a 1 unit AIT doses significantly improved DSS and DMS vs placebo ( P < .05).
Peak and entire season efficacy were comparable. The 12–Amb a 1 unit AIT dose reduced peak-season TCS vs placebo by 21% and 25% in subgroups with and without local application-site reactions, respectively.
Most treatment-related adverse events were mild, oral reactions; no systemic allergic reactions were reported.
One patient in the 6–Amb a 1 unit group received epinephrine at an emergency facility for sensation of localized pharyngeal edema.

55. Ragweed Slit in North American Adults
Total combined score plotted against pollen count
Nolte, H., et al. Annals Allergy, Asthma, Immunol. 2013;110:450-8

56. Ragweed Slit in North American Adults
Total combined score during the peak and entire ragweed season (RS)
% of patients reporting rescue medication use during peak ragweed season
*RS=ragweed season
Nolte, H., et al. Annals Allergy, Asthma, Immunol. 2013;110:450-8

57. Safety and tolerability of a short ragweed sublingual immunotherapy tablet
Methods:
Data from 4 randomized, double-blinded, placebo-controlled trials of MK-3641 (2 28-day and 2 52-week trials) were evaluated. Pooled analyses examined short-term safety over 28 days from all 4 trials and long-term safety from the 52-week trials.
Results:
Across studies,757,198,454,and1,058subjects were randomized to placebo or 1.5,6,or12Amba1-U ofMK-3641,respectively.
Treatment-related adverse events were more frequent in the 6-and12-Amba1-UMK-3641 groups than in the placebo group and were primarily local application-site reactions occurring in the first few days of treatment.
There was no treatment-associated loss of asthma control or worsening of asthma associated with treatment.
No swellings led to airway obstruction or respiratory compromise.
No treatment-related anaphylactic shock, life-threatening, or serious treatment-related adverse events were reported for any MK dose.
Of the 1,707 MK-3641-treated subjects,1 systemic (anaphylactic) reaction was reported (0.06%).
The 52-week long-term assessment was generally similar to the safety profile based on the 28-day assessment
Nolte Ann Allergy Asthma Immunol 2014;113:93-100

58. Table 4: Adverse event summary (all treated subjects) for pooled analyses
Nolte Ann Allergy Asthma Immunol 2014;113:93-100

59. Table 5 All treatment-related AE occurring in at least 5% of subjects in any treatment group in the pooled analyses
Nolte Ann Allergy Asthma Immunol 2014;113:93-100

60. Long-lasting effects of sublingual immunotherapy according to its duration: A 15-year prospective study
Methods:
In this prospective open controlled study we followed up patients with respiratory allergy who were monosensitized to mites for 15 years.
The subjects were divided in 4 groups receiving drug therapy alone or SLIT for 3, 4, or 5 years.
Clinical scores, skin sensitizations, methacholine reactivity, and nasal eosinophil counts were evaluated every year during the winter months.
The clinical effect was considered to persist until clinical scores remained at less than 50% of the baseline value, and then patients underwent another course of SLIT.
Marogna JACI 2010;126:969-75

61. Long-lasting effects of sublingual immunotherapy according to its duration: A 15-year prospective study
Results:
Seventy-eight patients were enrolled, and 59 completed the study.
In the 12 control subjects no relevant change in clinical scores was seen throughout the study.
In the patients receiving SLIT for 3 years, the clinical benefit persisted for 7 years.
In those receiving immunotherapy for 4 or 5 years, the clinical benefit persisted for 8 years.
New sensitizations occurred in all the control subjects over 15 years and in less than a quarter of the patients receiving SLIT (21%, 12%, and 11%, respectively).
The second course of vaccination induced a benefit more rapidly than the first course.
Marogna JACI 2010;126:969-75

62. FIG 2. Mean monthly SMSs (means and SDs) throughout the 15 years of the study in patients in the SLIT3 (A), SLIT4 (B), and SLIT5 (C) groups.
Marogna JACI 2010;126:969-75

63. FIG 4. Percentage of patients with at least 1 new skin sensitization in the SLIT3 (blue line), SLIT4 (red line), SLIT5 (green line), and control (black line) groups. The asterisk indicates the significant difference versus the control group.
Marogna JACI 2010;126:969-75

64. Anaphylaxis to SLIT Allergen Build-Up or Maintenance Symptoms
Reference
Multiple
Build-Up
Pruritus, wheezing, dizziness
Allergy 2006;61:1235
Maintenance
Urticaria, asthma, “anaphylactic shock”
Allergy 2007;62:567
HDM
Maintenance (3 yrs)
Urticaria, wheezing, hypotension, syncope
Allergy 2008;63:374
Grass (2)
1st Dose
Hypotension
Allergy 2009;64:963-4
No fatal or near-fatal reactions have been reported
FDA requires epipen

65. Lin et al.
AHRQ

66. Relative to a control group:
Evidence for the Efficacy and Effectiveness of Subcutaneous Immunotherapy in the Treatment of Rhinitis and Rhinoconjunctivitis
Key Points
Relative to a control group:
High grade evidence supports that subcutaneous immunotherapy improves rhinoconjunctivitis symptoms, based on 26 randomized controlled trials with subjects.
High grade evidence supports that subcutaneous immunotherapy improves conjunctivitis symptoms, based on 14 randomized controlled trials with subjects.
High grade evidence supports that subcutaneous immunotherapy improves control of combined nasal, ocular, and bronchial symptoms, based on six randomized controlled trials with 591 subjects.
Lin et al.
AHRQ

67. Evidence for the Efficacy and Effectiveness of Subcutaneous Immunotherapy in the Treatment of Rhinitis and Rhinoconjunctivitis
Key Points.
Moderate grade evidence supports that subcutaneous immunotherapy decreases rhinoconjunctivitis medication use, based on ten randomized controlled trials with 564 subjects
High grade evidence supports that subcutaneous immunotherapy decreases combined medication use (rhinitis/rhinoconjunctivitis plus asthma medication use), based on 11 randomized controlled trials with 768 subjects.
Low grade evidence supports that subcutaneous immunotherapy improves rhinoconjunctivitis (with or without asthma) combined symptom-medication scores, based on six randomized controlled trials with 400 subjects.
High grade evidence supports that subcutaneous immunotherapy improves disease specific quality of life, based on six randomized controlled trials with 889 subjects.
Lin et al.
AHRQ

68. Effectiveness of sublingual immunotherapy in the treatment of allergic rhinitis/rhinoconjunctivitis and/or asthma
Key Points • High grade evidence supports that sublingual immunotherapy improves asthma symptoms based on 13 randomized controlled trials with 625 subjects. • Moderate grade evidence supports that sublingual immunotherapy improves asthma or rhinitis/rhinoconjunctivitis (asthma combined scores) symptom control based on 5 randomized controlled trials with 308 subjects. • Moderate grade evidence supports that sublingual immunotherapy improves rhinitis/rhinoconjunctivitis symptoms based on 35 randomized controlled trials with 2658 subjects.

69. Effectiveness of sublingual immunotherapy in the treatment of allergic rhinitis/rhinoconjunctivitis and/or asthma
Key Points Moderate grade evidence supports that sublingual immunotherapy improves control of conjunctivitis symptoms based on 13 randomized controlled trials with 1074 subjects. • Moderate grade evidence supports that sublingual immunotherapy decreases medication use based on 38 randomized controlled trials with 2724 subjects. • Moderate grade evidence supports that sublingual immunotherapy improves allergy symptoms or decreases medication use based on 19 randomized controlled trials with 1462 subjects. • Moderate grade evidence supports that sublingual immunotherapy improves disease specific quality of life based on eight randomized controlled trials with 819 subjects.

70. Evidence for the safety of sublingual immunotherapy in patients with allergic rhinitis/rhinoconjunctivitis and/or asthma
Key Points • Local reactions (occurring at the site of allergen administration) were common across trials • Systemic reactions were uncommon • No life threatening systemic reactions or anaphylaxis were reported in these trials • No deaths were reported
Lin et al.
AHRQ

71. Real-life compliance and persistence among users of subcutaneous and sublingual allergen immunotherapy
Objective:
To assess levels and predictors of compliance and persistence among grass pollen, tree pollen, and house dust mite immunotherapy users in real life and to estimate the costs of premature discontinuation.
Methods:
performed a retrospective analysis of a community pharmacy database from The Netherlands containing data from 6486 patients starting immunotherapy for1 or more of the allergens of interest between 1994 and 2009.
Two thousand seven hundred ninety-six patients received SCIT,and 3690 received SLIT.
Time to treatment discontinuation was analyzed and included Cox proportional hazard models with time-dependent covariates, where appropriate.
Kiel JACI 2013;132:353-60

72. Real-life compliance and persistence among users of subcutaneous and sublingual allergen immunotherapy
Results:
Overall, only 18% of users reached the minimally required duration of treatment of 3 years (SCIT, 23%; SLIT, 7%).
Median durations for SCIT and SLIT users were 1.7 and 0.6 years, respectively (P < .001).
Other independent predictors of premature discontinuation were prescriber, with patients of general practitioners demonstrating longer persistence than those of allergologists and other medical specialists; single allergen immunotherapy, lower socioeconomic status; and younger age.
Of the persistent patients, 56% were never late in picking up their medication from the pharmacy.
Direct medication costs per non-persistent patient discontinuing in the third year of treatment were €3800, an amount that was largely misspent.
Kiel JACI 2013;132:353-60

73. Fig 2: Kaplan-Meier curse of time to treatment discontinuation by route of administration of allergen
Kiel JACI 2013;132:353-60

74. Studies Directly Comparing SLIT and SCIT Adherencea

75. Improved Adherence = Communicate and Educate
When the physician’s goal for AIT does not match the patient’s goal, adherence is likely to be poor
Differences in goals and patient expectations must be discussed and resolved before the treatment plan is finalized
Shared decision-making is a communication strategy to increase concordance about treatment choices and goals and leads to higher adherence in patients with asthma
Bender B, Oppenheimer J, J Allergy Clin: In Practice 2014;2:152-5.

76. Questions that still remain
Efficacy of SCIT vs. SLIT
Long term safety studies in SLIT
Will we need to prescribe AIE in the future
Multiple allergen sensitivity and SLIT
Other forms of IT
Intralymphatic IT