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Allergen
Immunotherapy:
An Update for
Primary-care Physicians
Faculty/Presenter Disclosure
Faculty/Presenter: [Dr. Shavinder Gill]
Relationships with commercial interests:
Grants/resea...
Declaration of conflict of interest as
per Canada Health.
• I do not directly owe shares of any of the
pharmaceutical comp...
Learning Objectives
After completing this program,
participants will be able to:
• Discuss the epidemiology and pathophysi...
Lessons learned at recent ACAAI
meeting.
• What is Epigenetics?
• What is beef-pork syndrome?
• What is cat-pork syndrome?...
Immunotherapy (IT) Overview
• Introduction to Allergic Rhinitis (AR)
• Subcutaneous Immunotherapy (SCIT)
• Sublingual Immu...
What are the two epidemics of last
few decades.?
• ?
What are the two epidemics of last
few decades?
• Allergic diseases. There was a 10 fold increase
i.e. 1000% increase in a...
What is the prevalence?
Epidemiology of
Allergic Rhinitis (AR)
• Affects 10-20% of population
• Often associated with asthma, atopic dermatitis,
f...
Pathophysiology of Allergic
Inflammation: Clinical Disease
Early-phase Reaction
Max. at 10-30 Minutes
American Academy of ...
Allergic Rhinitis (AR)
Seasonal Allergic Rhinitis (SAR)
• Tree, grass and ragweed
pollens
• Triggered by pollen in spring
...
AR Guidelines
LTRAs: leukotriene receptor antagonsists
*Step up if there is no response or incomplete response to treatmen...
Immunotherapy (IT) Overview
• Introduction to Allergic Rhinitis (AR)
• Subcutaneous Immunotherapy (SCIT)
• Sublingual Immu...
Which of the following is true?
• Immuno-therapy is affective in reducing the
incidence of asthma i.e prevent new asthma.
...
Which of the following is true?
• All of the above are true.
Which of the following is true?
• Immuno-therapy is affective in reducing the
incidence of asthma i.e prevent new asthma.
...
Subcutaneous Immunotherapy
• Immunotherapy has been used for 100 years
• Immune mechanisms of immunotherapy now
better def...
Long-term Clinical Efficacy of
Grass-pollen IT
• RCT of discontinuation of grass-pollen immunotherapy
(vs. continuation an...
Long-Term Clinical Efficacy of
Grass-Pollen Immunotherapy
Initial Placebo Trial Current Trial
PollenCount
(grains/m3)
Symp...
Long-term Clinical Efficacy of
Grass-pollen IT: Conclusions
• Immunotherapy for grass-pollen allergy for 3-4 years induces...
IT With a Standardized
D. pteronyssinus Extract
Specific IT prevents the onset of new sensitizations
in children(< 6 years...
Effects of Specific Immunotherapy in
AR Patients With Bronchial
Hyper-responsiveness
Grembiale RD, et al. Am J Respir Crit...
Children With and Without Asthma 7 Years
After Termination of Specific Immunotherapy
Jacobsen L, et al. Allergy 2007; 62(8...
(Abramson et al. AARD
1995;151)
Meta-Analysis of Immunotherapy for
Asthma
• Mites
– Smith (n=22)
– Maunsell (n=34)
– Werne...
Administering Subcutaneous IT (1)
Administering Subcutaneous IT (2)
Vial #0
1:1000
Vial #1
1:100
Vial #2
1:10
Vial #3
1:1
Dose mL Dose mL Dose mL Dose mL
1 0.10 6 0.10 11 0.05 17 0.05
2 0.20...
Time to Onset of Systemic Reactions
with Allergen Immunotherapy
Greineder DK. J Allergy Clin Immunol 1996; 98:S330-S334. [...
Immunotherapy Overview
• Introduction to Allergic Rhinitis (AR)
• Subcutaneous Immunotherapy (SCIT)
• Sublingual Immunothe...
Sublingual Immunotherapy
Tablet (SLIT-T)
• Novel treatment for AR in Canada
• Available to treat grass allergy
• Effective...
Rationale for Treatment with
Grass SLIT-T
Treatment of Allergic Rhinoconjunctivitis:
✓Reduction of symptoms in first polle...
Grass Sublingual
Immunotherapy Tablets
• Grastek (Merck-ALK)
– Phleum pratense (timothy grass pollen) 75,000
SQ-T (equival...
SLIT-T With Once-daily
Grass Allergen Tablets
• Multi-center randomized controlled trial (RCT)
• 855 subjects aged 18-65 y...
Immunologic Changes After Treatment
With Placebo or Grass Pollen Tablets
Before start
of treatment
Relativeunits(RU)
0.06
...
Efficacy and Safety of SLIT-T
With Grass Allergen Tablets
• 51 centers
• 634 patients with AR from grass for at least two
...
Mean Entire-season Rhinoconjunctivitis
Symptom Scores and Medication Scores
Dahl R, et al. J Allergy Clin Immunol 2006; 11...
Global Evaluation of
Treatment Effect
Treatment group
Grass allergen tablet
N (%)
Placebo
N (%)
No. of subjects 316 318
Ov...
Treatment-emergent Adverse Events
Reported by ≥ 5% of Subjects
Treatment group
Grass allergen tablet
N (%)
Placebo
N (%)
N...
Pollen Counts and Mean
Rhinoconjunctivitis Total Symptom
Scores (RTSS) by Study Arm
Didier A, et al. J Allergy Clin Immuno...
Is Grass SLIT-T Disease-modifying?
GT-08 Study
• Male and female subjects aged 18-65 years
• Clinical history ≥ 2 years of...
Sustained Effects of Grass Pollen
SLIT-T: GT-08 Study Design
Follow Up
Follow Up
Grass SLIT-T Treatment
2005 2007 2008 200...
Year 1
32%
Year 5
31%
Year 4
31%
Year 3
37%
Year 2
44%
Grass Pollen Tablet Long-term Efficacy
Effect sustained 2 years aft...
Prior to the First Dose
• Physician must be present with appropriate
resuscitation equipment
• Patients should be counsele...
Dose Administration
• Tablet should be placed under the tongue,
where it dissolves
• Instruct the patient not to swallow f...
Dose Administration (cont’d)
The first dose will be administered in the office with
a 30-minute observation period
• Obser...
SCIT vs. SLIT-T: Efficacy
SCIT SLIT-T
Efficacy shown in RCTs +++ +++
Mechanism of action identified +++ ++
Standardized do...
SCIT vs. SLIT-T: Safety
SCIT SLIT-T
Administration at home - +++
Risk anaphylaxis +++ +
Local side effects + ++
Use in ped...
Duration of Expected
Adverse Effects
Adverse Effect
Grass SLIT-T
(minutes)
Throat irritation 15-85
Oral pruritus 3-30
Ear ...
Immunotherapy Overview
• Introduction to Allergic Rhinitis (AR)
• Subcutaneous Immunotherapy (SCIT)
• Sublingual Immunothe...
When to Refer AR to an Allergist
• Symptoms of AR that are not adequately
responding to medical therapy
• Patient or refer...
AR Guidelines
LTRAs: leukotriene receptor antagonsists
*Step up if there is no response or incomplete response to treatmen...
Simplified AR Treatment Algorithm
Small and Kim. AACI Nov 2011.
Treatments can be used individually or in any combination
...
Questions to ask patient for AR
• Do you have nasal congestion, runniness and/or
sneezing?
• Do you have itchy, red and/or...
Approach to AR in your Office
• History should suggest AR
• Look for associated issues such as atopic
dermatitis, asthma, ...
AR: Key Messages
• AR is linked with asthma and conjunctivitis
• Allergen skin tests are the best diagnostic test to confi...
Immunotherapy Conclusions
• AR is common
• SCIT is effective in the treatment of AR
• SLIT-T is a new, effective treatment...
Case Study 1: Patient Presentation
• 45-year-old female works in office as VP of
software company
• SAR for 12 years from ...
Case Study 1: Discussion
• Consider referral to allergist
• Patient likely has grass as her major allergen
• If SLIT-T is ...
Case Study 2: Patient Presentation
• 27-year-old male
• Allergies to grass and dust mites
• Last injection one week ago
• ...
Case Study 2: Discussion
• Management of anaphylaxis in family practice
• After a reaction to immunotherapy, should
immuno...
Case Study 3: Patient Presentation
• 12-year-old boy
• Two-year history of severe rhinitis and
conjunctivitis from May to ...
Case Study 3: Discussion
• If a patient presents to you during the time of
severe symptoms, what are some treatment
option...
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DR Gill allergen immunotherapy apr 2nd, 2014

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  • This slide must be visually presented to the audience AND verbalized by the speaker.
  • This slide lists the Learning Objectives that were taken into account in the development of this program.
  • This presentation begins with an introduction to allergic rhinitis (AR) itself before discussing in detail subcutaneous immunotherapy (SCIT) and the sublingual immunotherapy tablet (SLIT-T). Finally, the presentation reviews some practical issues and considerations with SLIT-T related to the approach in family practice.
  • AR is a common problem with a wide ranging impact on sufferers. Patients with AR typically report disturbances in terms of overall quality of life, sleep, and school/work. Reference:Small P, Kim H. AACI, November 2011.
  • This slide depicts a simplified schematic representation of the natural history of AR. Specifically, the slide shows phase 2 (clinical disease); not shown is phase 1 (sensitization).The early response is dominated by activation of mast cells and release of mediators. After early response, most patients have cellular infiltration of the nasal mucosa that causes late inflammatory events including spontaneous recurrence of release of mediators (late-phase reaction), hyper-responsiveness to irritants, and increased responsiveness to allergen (priming). The inflammation can resolve spontaneously, cause a complication, or potentially lead to an irreversible form of chronic rhinitis.Reference:Naclerio RM. Allergic rhinitis. N Engl J Med 1991; 325(12):860-9.
  • Seasonal allergic rhinitis (SAR) occurs mainly during pollen seasons, often involving reactions to tree, grass and ragweed pollens. Perennial allergic rhinitis (PAR) occurs year-round and often involves reactions to house dust mites, cockroaches, molds and animal dander.Grass typically is at highest levels in mid summer in most of Canada.SAR and PAR often co-exist, and many people with PAR have seasonal triggers/flares.
  • Recent Canadian guidelines provide a useful algorithm for management of AR. In this diagram, recommended treatment approaches are presented starting at the bottom and moving up. Regardless of the severity of the AR, treatment should be stepped up if there is no response or an incomplete response with a particular approach.So, for example, the first step recommended for treatment of class I AR is allergen and irritant avoidance. If this is insufficient to provide symptom control, a non-sedating oral antihistamine may be used.The next recommendation after failure or inadequacy of antihistamine therapy is an intranasal corticosteroid. Leukotriene receptor antagonists are the next step up the treatment hierarchy. If these fail, oral steroids may be considered, but there is limited evidence to support their use. Patients who fail to respond to all these approaches may be candidates for immunotherapy. There is limited evidence to support antileukotrienes in class III and IV AR or to support oral steroids in class II AR, and none to support oral steroids in class III AR.If immunotherapy is unsuccessful, surgery may be an option.Reference:Small P, Frenkiel S, Becker A, et al. Rhinitis: A practical and comprehensive approach to assessment and therapy. J Otolaryngol 2007; 36(suppl 1):S5-S27.
  • The next part of this presentation provides details about subcutaneous immunotherapy (SCIT).
  • Immunotherapy has been used in medicine for about a century, while the mechanisms of this therapy have become better defined. Subcutaneous immunotherapy is now known to be effective in AR, asthma and atopic dermatitis, and to have disease-modifying benefits. However, it is also associated with major time commitment and with a significant risk of anaphylaxis.
  • When this study was conducted, pollen immunotherapy had been proven effective in selected patients with IgE-mediated seasonal AR, but it was not clear whether there was long-term benefit after the discontinuation of treatment.These investigators conducted a 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. 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. Scores for seasonal symptoms and the use of rescue anti-allergic medication, which included short courses of prednisolone, remained low after the discontinuation of immunotherapy, and there was no significant difference between patients who continued immunotherapy and those who discontinued it. Although there was a tendency for immediate sensitivity to allergen to return late after discontinuation, there was a sustained reduction in the late skin response and associated CD3+ T-cell infiltration and interleukin-4 messenger RNA expression.The investigators concluded that immunotherapy for grass-pollen allergy for three to four years induces prolonged clinical remission accompanied by a persistent alteration in immunologic reactivity.Reference:Durham SR, Walker SM, Varga EM, et al. Long-term clinical efficacy of grass-pollen immunotherapy. N Engl J Med 1999; 341(7):468-75.
  • These investigators concluded that immunotherapy for grass-pollen allergy for three to four years induces prolonged clinical remission accompanied by a persistent alteration in immunologic reactivity. Reference:Durham SR, Walker SM, Varga EM, et al. Long-term clinical efficacy of grass-pollen immunotherapy. N Engl J Med 1999; 341(7):468-75.
  • This prospective, nonrandomized study was carried out in a population of asthmatic children younger than 6 years of age whose only allergic sensitivity was to house dust mites (HDM), to determine whether specific immunotherapy (SIT) with standardized allergen extracts could prevent the development of new sensitizations over a three-year follow-up survey.The study involved 22 children mono-sensitized to HDM who were receiving SIT with standardized allergen extracts, and 22 age-matched controls who were mono-sensitized to HDM.Ten of 22 children mono-sensitized to HDM who were receiving SIT did not have new sensitivities, compared with none of the 22 children in the control group (p = 0.001, chi square test).The investigators concluded that their results suggest that SIT in children mono-sensitized to HDM alters the natural course of allergy in preventing the development of new sensitizations. Reference:Des Roches A, Paradis L, Menardo JL, et al. Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. VI. Specific immunotherapy prevents the onset of new sensitizations in children. J Allergy Clin Immunol 1997; 99(4):450-3.
  • This study showed that SCIT for house dust mites improves bronchial hyper-responsiveness and asthma in young adults receiving SCIT.The aim of the study was to evaluate the ability of specific immunotherapy to reduce the progression of AR to asthma and prevent the associated increase in bronchial hyper-responsiveness. A total of 44 subjects mono-sensitized to Dermatophagoides pteronyssinus, with perennial AR and bronchial hyper-responsiveness to methacholine, were randomly assigned to receive specific immunotherapy or placebo in a double-blind study conducted over a period of two years. After one year of treatment, a 2.88-fold increase in the provocative dose of methacholine producing a 20% decrease in FEV1 (PD20FEV1) was recorded in the specific immunotherapy group (95% CI 3.98-2.09; p &lt; 0.001), with a further increase to four-fold at the end of two years (95% CI 2.9-5.7; p &lt; 0.001). At the end of the study, the methacholine PD20FEV1 was within the normal range in 50% of treated subjects (p &lt; 0.0001), and was significantly higher in this group than in the group receiving placebo (p &lt; 0.0001). In contrast, no changes in methacholine PD20FEV1 were found in the placebo group throughout the study. Although 9% of subjects given placebo developed asthma, none of those treated with specific immunotherapy did. This study’s results suggested that specific immunotherapy, when administered to carefully selected, mono-sensitized patients with perennial AR, reduces airway responsiveness in subjects with rhinitis, and may be an appropriate prophylactic treatment for rhinitic patients with hyperreactive airways.Reference:Grembialie RD, Camporota L, Naty S, et al. Effects of specific immunotherapy in allergic rhinitic individuals with bronchial hyperresponsiveness. Am J Respir Crit Care Med 2000; 162(6):2048-52.
  • This study showed that treatment with SCIT in patients with AR resulted in less frequent asthma after long-term follow up.The investigators evaluated the long-term clinical effect and the preventive effect of developing asthma seven years after termination of subcutaneous specific immunotherapy. A cohort of 147 subjects, aged 16-25 years with grass and/or birch pollen allergy was investigated 10 years after initiation of a three-year course of specific immunotherapy with standardized allergen extracts of grass and/or birch or no specific immunotherapy. Conjunctival provocations were performed outside the season and methacholine bronchial provocations were performed during the season and winter. Asthma was assessed by clinical evaluation.Significant improvements in rhinoconjunctivitis and conjunctival sensitivity persisted at the 10-year follow-up. Significantly fewer actively treated subjects had developed asthma at 10-year follow-up as evaluated by clinical symptoms (OR 2.5; 1.1-5.9). Among controls, 24/53 subjects developed asthma, while in the specific immunotherapy group 16/64 subjects developed asthma. Reference:Jacobsen L, Niggermann B, Dreborg S, et al. Allergy 2007; 62(8):943-8.
  • Subcutaneous immunotherapy involves the injection of commercial allergen extracts via small hypodermic syringes.
  • Injections are typically administered into the loose tissue over the back of the upper arm, mid-way between the shoulder and elbow.
  • Subcutaneous specific immunotherapy is started at very low doses which are gradually increased on a regular (often weekly) basis until a (usually monthly) maintenance dose is reached. This slide presents a sample dose chart.
  • As reviewed by Greineder in 1996, the major risk of allergen immunotherapy is the development of systemic anaphylactic reactions. The reported frequency of systemic reactions after allergen immunotherapy varies from &lt; 1% in patients receiving conventional immunotherapy to &gt; 36% in patients receiving “rush” immunotherapy. Fatal and systemic reactions to allergen immunotherapy have similar characteristics. As shown in this graph, the onset of systemic reaction occurs within 30 minutes after injection in approximately 70% of patients. Precautions during allergen immunotherapy have been recommended, and interventions such as pre-medication with antihistamines or corticosteroids, measurement of peak flow before injection, and access to an antihistamine or injectable epinephrine after an allergen injection have been suggested as measures to prevent reactions to and improve the safety of allergen immunotherapy.Reference:Greineder DK. Risk management in allergen immunotherapy. J Allergy Clin Immunol 1996; 98(6 Pt 3):S330-S334. [Data from Matloff SM, Bailit IW, Parks P, et al. Systemic reactions to immunotherapy. Allergy Proc 1993; 14(5):347-50.]
  • The next part of this presentation provides details about sublingual immunotherapy via sublingual immunotherapy tablet (SLIT-T).
  • The sublingual immunotherapy tablet (SLIT-T) represents a novel treatment choice in Canada for AR, available for the treatment of grass allergy.As will be discussed, SLIT-T has been shown to be effective in children and adults, and to have disease-modifying effects. This therapy can be taken by patients at home (following the first dose in the clinic with an observation period), and associated with minimal risk of anaphylaxis.
  • For patients with grass allergy, there are several factors supporting the role for specific immunotherapy via SLIT-T. Specifically in terms of treating allergic rhinoconjunctivitis, grass SLIT-T can reduce symptoms in the first pollen season and the need for pharmacologic treatment, and is safe for self-administration. Furthermore, grass SLIT-T provides sustained efficacy during treatment as well as disease-modifying effect and prevention of disease progression following treatment.
  • The two grass SLIT-T products being made available in Canada are listed here.
  • In this multinational, multicenter, randomized, placebo-controlled trial conducted during 2002-2003, the efficacy and safety of sublingual grass allergen tablets in seasonal allergic rhinoconjunctivitis were examined.A total of 855 participants (from 55 centers in eight countries), aged 18-65 years, gave a history of grass pollen-induced allergic rhinoconjunctivitis and had a positive skin prick test and elevated serum allergen-specific IgE to Phleum pratense. Participants were randomized to 2,500, 25,000, or 75,000 SQ-T grass allergen tablets or placebo for sublingual administration once daily. Mean duration of treatment was 18 weeks.Average rhinoconjunctivitis scores during the season showed moderate reductions of symptoms (16%) and medication use (28%) for the grass allergen tablet 75,000 SQ-T (p = 0.0710 and p = 0.0470, respectively) compared with placebo. Significantly better rhinoconjunctivitis quality of life scores (p = 0.006) and an increased number of well days (p = 0.041) were also observed. Efficacy was increased in the subgroup of patients who completed the recommended pre-seasonal treatment of at least 8 weeks before the grass pollen season (symptoms 21%, p = 0.0020; and medication use 29%, p = 0.0120). No safety concerns were observed.Reference:Durham SR, Yang WH, Pedersen MR, et al. Sublingual immunotherapy with once-daily grass allergen tablets: a randomized controlled trial in seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 2006; 117(4):802-9.
  • In the 75,000 SQ-T group, specific IgG to P. pratense was increased after 8 weeks of treatment and reached a 3-fold increase at the post-treatment visit (panel A). For specific IgE, an initial increase was observed and then no further change at the post-treatment visit (panel B). In the placebo group, the expected seasonal increase in IgE was also observed.Reference:Durham SR, Yang WH, Pedersen MR, et al. Sublingual immunotherapy with once-daily grass allergen tablets: a randomized controlled trial in seasonal allergic rhinoconjunctivitis. J Allergy ClinImmunol 2006; 117(4):802-9.
  • This longitudinal, double-blind, placebo-controlled, parallel-group study was aimed at confirming the efficacy of a rapidly dissolving grass allergen tablet compared with placebo in patients with seasonal rhinoconjunctivitis.The study included 634 subjects from 51 centers in eight countries. Subjects were randomized (1:1) to receive a grass allergen tablet or placebo once daily. Each had a history of grass pollen-induced rhinoconjunctivitis for at least two years and confirmation of IgE sensitivity (positive skin prick test and serum-specific IgE). Subjects commenced treatment at least 16 weeks before the grass pollen season, and treatment was continued throughout the entire season.The primary efficacy analysis showed a reduction of 30% in rhinoconjunctivitis symptom score (p &lt; 0.0001) and a reduction of 38% in rhinoconjunctivitis medication score (p &lt; 0.0001) compared with placebo. Side effects mainly comprised mild itching and swelling in the mouth that was generally well tolerated and led to treatment withdrawal in less than 4% of participants. There were no serious local side effects and no severe systemic AEs.Reference:Dahl R, Kapp A, Colombo G, et al. Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 2006; 118(2):434-40.
  • A total of 634 subjects were randomized, and 546 (86%) completed the first treatment year. In total, 88 subjects (14%) withdrew, 24 (4%) because of AEs. The pattern of withdrawal was similar between groups, but with nominally more withdrawals due to AEs in the grass-allergen-tablet group. Reference:Dahl R, Kapp A, Colombo G, et al. Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 2006; 118(2):434-40.
  • The study population was made up of 59% male subjects and 41% female subjects. A total of 44% of subjects had moderate grass pollen allergy and 56% had severe grass pollen allergy. The average history of grass pollen allergy was 16 years, the average subject was 34.2 years of age, and overall subject characteristics were similar between groups.Reference:Dahl R, Kapp A, Colombo G, et al. Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis. J Allergy ClinImmunol 2006; 118(2):434-40.
  • These graphs show mean symptom scores and medication scores for the entire grass pollen season. As mentioned, rhinoconjunctivitis symptom score and medication score were significantly reduced in the SLIT-T group compared to the placebo group.Reference:Dahl R, Kapp A, Colombo G, et al. Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 2006; 118(2):434-40.
  • At the end of the 2005 grass pollen season, subjects were asked, “Compared to your rhinoconjunctivitis symptoms in previous grass pollen seasons, how have you felt overall in this grass pollen season?”This table summarizes the responses. Data were pooled into the binary endpoint of “improved” or “not improved.” As shown, 82% of subjects who received active treatment indicated improvement, compared to 55% of placebo subjects (an overall improvement in the response rate of 49%; p &lt; 0.0001).Reference:Dahl R, Kapp A, Colombo G, et al. Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 2006; 118(2):434-40.
  • No serious AEs with possible or probable relation to the study drug were reported. As shown here, the majority of the most frequently reported AEs were application-site-related, indicating drug relationship. Other common AEs such as headache, nasopharyngitis and influenza were equally reported in both groups. Reference:Dahl R, Kapp A, Colombo G, et al. Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 2006; 118(2):434-40.
  • The 300-index of reactivity (IR) and 500-IR doses significantly reduced mean Rhinoconjunctivitis Total Symptom Score (3.58 ± 3.0, p = 0.0001; and 3.74 ± 3.1, p = 0.0006, respectively) compared with placebo (4.93 +/- 3.2) in the intent-to-treat and per-protocol analyses. The 100-IR group (4.70 +/- 3.1) score was not significantly different from placebo. Reference:Didier A, Malling HJ, Worm M, et al. Optimal dose, efficacy and safety of once-daily sublingual immunotherapy with a 5-grass pollen tablet for seasonal allergic rhinitis. J Allergy Clin Immunol 2007; 120(6):1338-45.
  • These investigators aimed to determine sustained efficacy one year after a three-year period of daily treatment with the SQ-standardized grass allergy immunotherapy tablet (Phleum pratense 75,000 SQ-T/2,800 BAU).A randomized, double-blind, placebo-controlled, phase III trial including adults with a history of moderate-to-severe grass pollen induced rhinoconjunctivitis inadequately controlled by symptomatic medications. The analysis set comprised 257 subjects at the follow-up. Efficacy endpoints were rhinoconjunctivitis symptom and medication scores, quality of life, and percentages of symptom and medication free days. Immunologic end points included grass pollen-specific serum IgG4 and IgE-blocking factor. Safety was assessed based on AEs.Reference:Durham SR, Emminger W, Kapp A, et al. Long-term clinical efficacy in grass pollen-induced rhinoconjunctivitis after treatment with SQ-standardized grass allergy immunotherapy tablet. J Allergy Clin Immunol 2010; 125(1):131-8.
  • This slide shows the study’s subject disposition.From originally one year of treatment, the trial was extended to cover three years of treatment and two years of follow-up to investigate long-term and sustained efficacy. Reference:Durham SR, Emminger W, Kapp A, et al. Long-term clinical efficacy in grass pollen-induced rhinoconjunctivitis after treatment with SQ-standardized grass allergy immunotherapy tablet. J Allergy Clin Immunol 2010; 125(1):131-8.
  • Persistent clinical efficacy was accompanied by prolonged increases in allergen-specific IgG(4) antibodies and IgE-blocking factor, confirming clinical and immunological tolerance for at least two years after the treatment completion. No safety issues were identified during follow-up.Reference:Durham SR, et al. Sustained effects of grass pollen AIT. Allergy 2011; 66 (Suppl 95):50-52.
  • Data from the fifth year of the GT-08 study documented that the positive clinical effect of treatment with the grass SLIT-T was sustained even after two years following completion of treatment. In the second follow-up year following end of treatment (study year 5), symptoms were significantly reduced by a median of 31% compared to placebo. These positive findings were obtained despite subjects requiring a lower use of symptomatic medications compared with the placebo group. There was a 21% reduction compared to placebo in terms of symptomatic medication use in the grass SLIT-T group; actual use of symptomatic medications was very low during the 2009 study season for both groups. Consequently, no significant difference was found.Reference:Durham SR, Emminger W, Kapp A, et al. Long-term clinical efficacy in grass pollen-induced rhinoconjunctivitis after treatment with SQ-standardized grass allergy immunotherapy tablet. J Allergy Clin Immunol 2010; 125(1):131-8.
  • Several steps can help to ensure that the initiation of SLIT-T goes smoothly and is well tolerated by patients. Preparing patients by explaining to them the symptoms they might experience is an important part of this process. This will make patients less anxious in advance of the initial dose, and less apprehensive about symptoms they experience during the initial and subsequent doses.Expected reactions should be reviewed again during follow-up phone calls, and if possible the timing of these calls should occur around the timing of the dosing.
  • Regarding administration of SLIT-T, the tablet should be placed under the patient’s tongue, where it will dissolve. Patients should be instructed to avoid swallowing for one minute, and to avoid eating and drinking for 10 minutes after placing the tablet under their tongue. The SLIT-T should be administered at approximately the same time each day.
  • The first SLIT-T dose will be administered in the office/clinic, with a 30-minute observation period. This observation period should be extended if the patient experiences a significant adverse reaction, and if further attention is required for treatment of such a reaction which cannot be provided at the office/clinic the patient should be transferred to an appropriate facility.
  • Efficacy with SCIT and SLIT-T have been shown equally in respective randomized controlled trials. The mechanism of action of SCIT has been slightly more fully identified, while standardized dosing in randomized trials has been somewhat better established for SLIT-T. Both forms of specific immunotherapy have demonstrated disease-modifying properties.
  • In terms of safety, it is important to note that SLIT-T (but not SCIT) can be administered by patients at home (following the initial dose), and that SLIT-T is associated with lower risk of anaphylactic reaction. SLIT-T may have slightly more local side effects, but is also slightly safer for use in pediatric patients.
  • These expected adverse reactions to grass SLIT-T typically occur with the first several doses and then diminish over time as the regimen continues. This table shows the usual duration of these reactions when they do occur.
  • The final section of this presentation discusses some of the practical issues and considerations regarding the use of SLIT-T, related to the approach in family practice.
  • Referral of patients with AR to an allergist may be warranted when symptoms are not completely responding to medical therapy, when the patient or referring physician would like to identify specific allergic triggers (and the patient can avoid identified triggers), and/or when immunotherapy is being considered.
  • Recent Canadian guidelines provide a useful algorithm for management of AR. In this diagram, recommended treatment approaches are presented starting at the bottom and moving up. Regardless of the severity of the AR, treatment should be stepped up if there is no response or an incomplete response with a particular approach.So, for example, the first step recommended for treatment of class I AR is allergen and irritant avoidance. If this is insufficient to provide symptom control, a non-sedating oral antihistamine may be used.The next recommendation after failure or inadequacy of antihistamine therapy is an intranasal corticosteroid. Leukotriene receptor antagonists are the next step up the treatment hierarchy. If these fail, oral steroids may be considered, but there is limited evidence to support their use. Patients who fail to respond to all these approaches may be candidates for immunotherapy. There is limited evidence to support antileukotrienes in class III and IV AR or to support oral steroids in class II AR, and none to support oral steroids in class III AR.If immunotherapy is unsuccessful, surgery may be an option.Reference:Small P, Frenkiel S, Becker A, et al. Rhinitis: A practical and comprehensive approach to assessment and therapy. J Otolaryngol 2007; 36(suppl 1):S5-S27.
  • This slide presents a simplified algorithm for AR treatment, highlighting a central role of intranasal corticosteroids since these are the mainstay of therapy for a majority of patients who present to physicians with AR. The algorithm depicts that these treatments can be used individually or in any combination with each other.Reference:Small P, Kim H. AACI, November 2011.
  • In consulting with patients with AR in whom immunotherapy is being considered or might be an option, the answers to these questions can be useful in helping to guide the next step in their treatment.
  • Patient history plays an important role in assessing suspected AR in primary care. After assessing for the presence of associated issues as listed here, and perhaps after a trial of non-sedating antihistamines or intranasal corticosteroids, referral should be made when deemed appropriate.
  • It is important to remember that AR is linked strongly with asthma and with conjunctivitis, and that allergen skin testing is the best diagnostic tool to confirm AR. The step-up treatment approach to AR begins with allergen/irritant avoidance, but intranasal corticosteroids are the mainstay of treatment for most patients who present to physicians with AR. Allergen immunotherapy can play an important role if pharmacologic therapy for AR is not effective or is not tolerated. Reference:Small P, Kim H. AACI, November 2011.
  • In summary, AR is a common problem with an important impact on the quality of life of sufferers. SLIT-T represents a good option for many patients with AR, as it has been shown to be safe and effective, is suitable for pediatric use, and can be administered at home.
  • This example represents a typical patient who might be seen in family practice.
  • In this patient, referral to an allergist should be considered. Her major allergen is most likely grass, and if SLIT-T is to be considered she should be seen by an allergist in December or earlier to arrange for timely initiation before the next grass pollen season.
  • This is another example of a situation which might arise in family practice.
  • Questions to consider in this case include whether immunotherapy should be continued after a patient has had a reaction, and how to manage a patient who wants to discontinue subcutaneous immunotherapy.
  • This is another example of a type of patient that might be seen in family practice.
  • Questions to consider in this case include the treatment options during severe symptoms, options for further testing, and the role/timing of referral.
  • Transcript of "DR Gill allergen immunotherapy apr 2nd, 2014"

    1. 1. Allergen Immunotherapy: An Update for Primary-care Physicians
    2. 2. Faculty/Presenter Disclosure Faculty/Presenter: [Dr. Shavinder Gill] Relationships with commercial interests: Grants/research support: [None] Speaker’s bureau/honoraria: Merck, Pfizer, Takeda, Novartis] Consulting fees: [None] Other: [None]
    3. 3. Declaration of conflict of interest as per Canada Health. • I do not directly owe shares of any of the pharmaceutical company. • I have given lectures/talks for pharmaceutical companies in the last several years but have donated that money to non-profitable organizations.
    4. 4. Learning Objectives After completing this program, participants will be able to: • Discuss the epidemiology and pathophysiology of allergic rhinitis. • Understand practice guidelines for the treatment of allergic rhinitis including the role of immunotherapy. • Compare subcutaneous and sublingual immunotherapy for allergic rhinitis. • Describe the process for initiation and administration of immunotherapy in patients with allergic rhinitis.
    5. 5. Lessons learned at recent ACAAI meeting. • What is Epigenetics? • What is beef-pork syndrome? • What is cat-pork syndrome? • What is pollen food allergy syndrome? • What is allergic eosinophillic oesophagitis?
    6. 6. Immunotherapy (IT) Overview • Introduction to Allergic Rhinitis (AR) • Subcutaneous Immunotherapy (SCIT) • Sublingual Immunotherapy Tablet (SLIT-T) • Approach in Family Practice
    7. 7. What are the two epidemics of last few decades.? • ?
    8. 8. What are the two epidemics of last few decades? • Allergic diseases. There was a 10 fold increase i.e. 1000% increase in allergic diseases in 1960’s and 1970’s. • Metabolic syndrome.
    9. 9. What is the prevalence?
    10. 10. Epidemiology of Allergic Rhinitis (AR) • Affects 10-20% of population • Often associated with asthma, atopic dermatitis, food allergy • Impacts quality of life, sleep, work • National and international guidelines available Small and Kim. AACI Nov 2011.
    11. 11. Pathophysiology of Allergic Inflammation: Clinical Disease Early-phase Reaction Max. at 10-30 Minutes American Academy of Otolaryngology, 2006. Adapted from: Naclerio RM. N Engl J Med 1991; 325(12):860-9. Late-phase Reaction Max. at 10-12 Hours Allergens Sneezing Rhinorrhea Congestion Mast cell IgE antibodies Mediator release Blood vessels Nerves Glands Cellular infiltration Eosinophils Basophils Monocytes Lymphocytes Resolution Complications Irreversible disease (?) Late-phase reaction Priming Hyper- responsiveness
    12. 12. Allergic Rhinitis (AR) Seasonal Allergic Rhinitis (SAR) • Tree, grass and ragweed pollens • Triggered by pollen in spring through fall seasons Perennial Allergic Rhinitis (PAR) • Dust mites, cockroaches, molds and animal dander • Chronic condition
    13. 13. AR Guidelines LTRAs: leukotriene receptor antagonsists *Step up if there is no response or incomplete response to treatment, regardless of class †LTRAs may be used in class III and IV, but there is less supporting evidence **Oral steroids may be considered for class II (severe intermittent), but there is little supporting evidence * Class I Class II Class III Class IV Allergen / irritant avoidance Oral H1 antihistamines Intranasal corticosteroids LRTAs† Oral steroids Immunotherapy Surgery Adapted from: Small P, et al. J Otolaryngol 2007; 36 (Suppl 1):S5-S27.
    14. 14. Immunotherapy (IT) Overview • Introduction to Allergic Rhinitis (AR) • Subcutaneous Immunotherapy (SCIT) • Sublingual Immunotherapy Tablet (SLIT-T) • Approach in Family Practice
    15. 15. Which of the following is true? • Immuno-therapy is affective in reducing the incidence of asthma i.e prevent new asthma. • It prevents new sensitization. • It is more economical than medication. • It does not work for food allergy. • It has long term efficacy after discontinuing the treatment.
    16. 16. Which of the following is true? • All of the above are true.
    17. 17. Which of the following is true? • Immuno-therapy is affective in reducing the incidence of asthma i.e prevent new asthma. True. It reduces the risk by 50%. • It prevents new sensitization. True • It is more economical than medication. True • It does not work for food allergy. True. Except for Oral allergy syndrome. • It has long term efficacy after discontinuing the treatment. True. Efficacy remains several years after stopping the vaccine.
    18. 18. Subcutaneous Immunotherapy • Immunotherapy has been used for 100 years • Immune mechanisms of immunotherapy now better defined • Effective in AR, asthma, atopic dermatitis and possibly Oral allergy syndrome/Pollen food allergy syndrome. • Has disease-modifying benefits • Drawbacks: time commitment and very small but significant risk of anaphylaxis.
    19. 19. Long-term Clinical Efficacy of Grass-pollen IT • RCT of discontinuation of grass-pollen immunotherapy (vs. continuation and vs. controls) in patients with history of severe seasonal AR • Conclusion: SCIT for 3-4 years for grass-pollen allergy induces prolonged clinical remission accompanied by a persistent alteration in immunologic reactivity Durham SR, et al. N Engl J Med 1999; 341:468-75.
    20. 20. Long-Term Clinical Efficacy of Grass-Pollen Immunotherapy Initial Placebo Trial Current Trial PollenCount (grains/m3) Symptom Score May June July Aug . May June July Aug . May June July Aug . May June July Aug .1989 1993 1994 1995 Study group Immunotherapy Placebo Immunotherapy Maintenance Discontinuation None (control)
    21. 21. Long-term Clinical Efficacy of Grass-pollen IT: Conclusions • Immunotherapy for grass-pollen allergy for 3-4 years induces prolonged clinical remission accompanied by a persistent alteration in immunologic reactivity Durham SR, et al. N Engl J Med 1999; 341:468-75.
    22. 22. IT With a Standardized D. pteronyssinus Extract Specific IT prevents the onset of new sensitizations in children(< 6 years old, asthma) Des Roches A, et al. J Allergy Clin Immunol 1997; 99(4):450-3. New Sensitivities Initial sensitivity Number of patients None Cat Dog Alt Grass SIT 22 10 6 4 2 1 Control 22 0 12 8 6 6
    23. 23. Effects of Specific Immunotherapy in AR Patients With Bronchial Hyper-responsiveness Grembiale RD, et al. Am J Respir Crit Care Med 2000; 162(6):2048-52. PD20FEV1(µmolofmethacholine) 1 0.1 10 Baseline 1st year 2nd year SIT p = 0.0008 p = 0.0001 PD20FEV1(µmolofmethacholine) 1 0.1 10 Baseline 1st year 2nd year Placebo p = NS p = NS
    24. 24. Children With and Without Asthma 7 Years After Termination of Specific Immunotherapy Jacobsen L, et al. Allergy 2007; 62(8):943-8. Based on patients without asthma before treatment (n = 119), absolute numbers of children shown above bars Mean age 21 years at 10-year follow-up Percentofpatients 90 0 80 70 60 50 100 40 30 20 10 SIT No asthma Asthma Odds-ratio = 2.5 (1.1 – 5.9) n = 48 n = 16 25% Control n = 29 n = 24 45%
    25. 25. (Abramson et al. AARD 1995;151) Meta-Analysis of Immunotherapy for Asthma • Mites – Smith (n=22) – Maunsell (n=34) – Werner (n=51) – D’Souza (n=91) – Pauli (n=18) – Newton (n=14) – BTA (n=56)  Other Allergens – Frankland (n=57) – Ohman (n=17) – Sundin (n=39) – Valovirta (n=27) • Mites Combined (n=286)  Other Allergens (n=140)  All Studies (n=426)0.1 1 10 100 1000
    26. 26. Administering Subcutaneous IT (1)
    27. 27. Administering Subcutaneous IT (2)
    28. 28. Vial #0 1:1000 Vial #1 1:100 Vial #2 1:10 Vial #3 1:1 Dose mL Dose mL Dose mL Dose mL 1 0.10 6 0.10 11 0.05 17 0.05 2 0.20 7 0.20 12 0.10 18 0.07 3 0.30 8 0.30 13 0.20 19 0.10 4 0.40 9 0.40 14 0.30 20 0.15 5 0.50 10 0.50 15 0.40 21 0.20 16 0.50 22 0.25 ***Hollister-Stier Extract*** Note: Record all injections in the treatment record. Note: This dosage chart is offered as a suggested schedule. However, the degree of sensitivity varies in many individuals. In these cases, the size of the dose and intervals between doses may have to be adjusted and should be regulated by the patient’s tolerance and reaction. Treatment is normally started with the weakest dilution in the set. Beginning with dose #1 as listed in the schedule. Doses should be administered at weekly or twice-weekly (at least two days apart) intervals while working up. The maintenance level is […] 23 0.30 24 0.35 25 0.40 26 0.45 27 0.50 Gradually increase intervals to monthly maintenance. *Please read text to left* Subcutaneous IT: Sample Dose Chart Dr.: Patient: Content: Lot No.: Expiry Date: This is a suggested dose chart only. Please read the instructions before commencing desensitization. Observe patients for 30 minutes after each injection. Check extract dilution and dose: Check the patient for local or systemic reaction(s) to previous injection.
    29. 29. Time to Onset of Systemic Reactions with Allergen Immunotherapy Greineder DK. J Allergy Clin Immunol 1996; 98:S330-S334. [Data from Matloff et al. Allergy Proc 1993; 14:347-50.] Time not recorded 10% 2-24 hours 8% 60-120 minutes minimum 2% 0-30 minutes 72% 30-60 minutes 8% Note: based on this, patients should be advised that they must wait 30 minutes in the clinic after receiving subcutaneous immunotherapy
    30. 30. Immunotherapy Overview • Introduction to Allergic Rhinitis (AR) • Subcutaneous Immunotherapy (SCIT) • Sublingual Immunotherapy Tablet (SLIT-T) • Approach in Family Practice
    31. 31. Sublingual Immunotherapy Tablet (SLIT-T) • Novel treatment for AR in Canada • Available to treat grass allergy • Effective in children and adults • Has disease-modifying effects • At-home therapy with minimal risk of anaphylaxis
    32. 32. Rationale for Treatment with Grass SLIT-T Treatment of Allergic Rhinoconjunctivitis: ✓Reduction of symptoms in first pollen season ✓Reduction of need for pharmacologic treatment ✓Safe for self-administration Sustained Efficacy During Treatment: ✓Maintenance of treatment effect during IT Long-term Efficacy: ✓Disease-modifying effect post-treatment ✓Prevention of disease progression (e.g., asthma)1 Novembre E, et al. J Allergy Clin Immunol 2004; 114(4):851-7.
    33. 33. Grass Sublingual Immunotherapy Tablets • Grastek (Merck-ALK) – Phleum pratense (timothy grass pollen) 75,000 SQ-T (equivalent to 2,800 BAU) for the treatment of Timothy and cross-reactive Rye, Meadow Fescue, Bluegrass,Cocksfoot and Sweet Vernal grasses. • Oralair (Stallergenes SA) – contains 5 grass pollens
    34. 34. SLIT-T With Once-daily Grass Allergen Tablets • Multi-center randomized controlled trial (RCT) • 855 subjects aged 18-65 years • Grass SLIT-T doses: 2,500, 25,000, 75,000 SQ-T • 18 weeks mean duration of treatment • AR score 18% better and medication use 28% better in the 75,000 SQ-T group (vs. placebo) • If > 8 weeks before grass season, symptoms 21% better and medication use 29% better (vs. placebo) Durham SR, et al. J Allergy Clin Immunol 2006; 117:802-9.
    35. 35. Immunologic Changes After Treatment With Placebo or Grass Pollen Tablets Before start of treatment Relativeunits(RU) 0.06 0 0.05 0.04 0.03 0.07 Placebo 2,500 SQ-T 0.02 0.01 A) Mean IgG Post-treatmentAfter approximately 8 weeks of treatment 25,000 SQ-T 75,000 SQ-T Before start of treatment kU/L 100 0 80 60 40 120 20 B) Mean IgE Post-treatmentAfter approximately 8 weeks of treatment Durham SR, et al. J Allergy Clin Immunol 2006; 117:802-9.
    36. 36. Efficacy and Safety of SLIT-T With Grass Allergen Tablets • 51 centers • 634 patients with AR from grass for at least two years • Treatment: SLIT-T 75,000 SQ-T at least 16 weeks pre-season and during season • Primary endpoint: 30% reduction symptoms and 38% reduction medications • Side effects generally mild • Treatment withdrawal 4% Dahl R, et al. J Allergy Clin Immunol 2006; 118(2):434-40.
    37. 37. Mean Entire-season Rhinoconjunctivitis Symptom Scores and Medication Scores Dahl R, et al. J Allergy Clin Immunol 2006; 118(2):434-40. Placebo Grass allergen tablet Meanscore 2.5 2.0 1.5 0 3.5 3.0 Entire-season Rhinoconjunctivitis Symptom Score 1.0 0.5 4.0 30% reduction p < 0.00013.4 2.4 Placebo Grass allergen tablet Meanscore 2.5 2.0 1.5 0 3.5 3.0 Entire-season Rhinoconjunctivitis Medication Score 1.0 0.5 4.0 38% reduction p < 0.0001 2.4 1.5
    38. 38. Global Evaluation of Treatment Effect Treatment group Grass allergen tablet N (%) Placebo N (%) No. of subjects 316 318 Overall assessment of 2005 compared with previous seasons N 278 275 Much better 96 (35) 45 (16) Better 132 (47) 106 (39) The same 41 (15) 89 (32) Worse 7 (3) 25 (9) Much worse 2(1) 10 (4) Improved 228 (82) 151 (55) Not improved 50 (18) 124 (45) Dahl R, et al. J Allergy Clin Immunol 2006; 118(2):434-40.
    39. 39. Treatment-emergent Adverse Events Reported by ≥ 5% of Subjects Treatment group Grass allergen tablet N (%) Placebo N (%) No. of subjects 316 318 Oral pruritus 145 (46) 13 (4) Nasopharyngitis 47 (15) 60 (19) Edema mouth 58 (18) 2 (1) Influenza 23 (7) 24 (8) Ear pruritus 38 (12) 3 (1) Throat irritation 30 (9) 3 (1) Headache 9 (3) 19 (6) Dahl R, et al. J Allergy Clin Immunol 2006; 118(2):434-40.
    40. 40. Pollen Counts and Mean Rhinoconjunctivitis Total Symptom Scores (RTSS) by Study Arm Didier A, et al. J Allergy Clin Immunol 2007; 120(6):1338-45. Days (0 = first day of main pollen period) MeanRTSS 4 3 0 5 2 1 6 Pollencounts/m3/24h 100 90 80 70 60 50 40 30 20 10 0 50454035302520152050-5-10-15-20-25 Placebo 100-IR 300-IR 500-IR Pollen count Daily mean symptom scores are plotted as one curve by treatment group with the corresponding scale on the left vertical axis. Daily mean grass pollen counts are plotted as shaded area and the corresponding scale is on the right vertical axis.
    41. 41. Is Grass SLIT-T Disease-modifying? GT-08 Study • Male and female subjects aged 18-65 years • Clinical history ≥ 2 years of grass-pollen-induced rhinoconjunctivitis • Clinical history of moderate to severe rhinoconjunctivitis symptoms (interfering with usual daily activities or sleep), despite treatment with symptomatic medications during the grass pollen season • Positive Phleum pratense SPT (wheal ≥ 3mm) and specific IgE (≥ class 2) • FEV1 ≥ 70% predicted • No symptomatic seasonal allergic rhinoconjunctivitis due to tree/weed pollen adjacent or overlapping the grass pollen season or active perennial allergic rhinoconjunctivitis (note that approximately 80% of subjects were multi-sensitized) Durham SR, et al. J Allergy Clin Immunol 2010; 125(1):131-8.
    42. 42. Sustained Effects of Grass Pollen SLIT-T: GT-08 Study Design Follow Up Follow Up Grass SLIT-T Treatment 2005 2007 2008 20092006 Placebo Treatment End of treatment Durham SR, et al. Allergy 2011; 66 (Suppl 95):50-52.
    43. 43. Year 1 32% Year 5 31% Year 4 31% Year 3 37% Year 2 44% Grass Pollen Tablet Long-term Efficacy Effect sustained 2 years after treatment Durham SR, et al. J Allergy Clin Immunol 2010; 125:231-8. Total daily rhinoconjunctivitis symptom score (median values) Symptomscore(median) 4 0 3 2 1 5 Placebo Grass SLIT-T End of treatment
    44. 44. Prior to the First Dose • Physician must be present with appropriate resuscitation equipment • Patients should be counseled that they may feel itching in the mouth or throat, swelling in and around the mouth, itching in the ears – these sensations typically self-resolve over 30 minutes – over time, the sensations occur less frequently • Proper oral examination should be completed – SLIT-T may be contraindicated in patients with severe inflammatory conditions in the oral cavity
    45. 45. Dose Administration • Tablet should be placed under the tongue, where it dissolves • Instruct the patient not to swallow for 1 minute • Instruct the patient to avoid eating and drinking for 10 minutes • Should be administered daily at approximately the same time each day
    46. 46. Dose Administration (cont’d) The first dose will be administered in the office with a 30-minute observation period • Observation period should be extended if significant AEs occur • If further attention is required for the treatment of an AE and such treatment cannot be provided at the office/clinic, the patient should be transferred to an appropriate facility
    47. 47. SCIT vs. SLIT-T: Efficacy SCIT SLIT-T Efficacy shown in RCTs +++ +++ Mechanism of action identified +++ ++ Standardized dosing in RCTs ++ +++ Disease-modifying ++ ++
    48. 48. SCIT vs. SLIT-T: Safety SCIT SLIT-T Administration at home - +++ Risk anaphylaxis +++ + Local side effects + ++ Use in pediatrics + ++
    49. 49. Duration of Expected Adverse Effects Adverse Effect Grass SLIT-T (minutes) Throat irritation 15-85 Oral pruritus 3-30 Ear pruritus 15-30 Mouth edema 15-75 Onset typically occurs with the first several doses of treatment. Events typically diminish over time.
    50. 50. Immunotherapy Overview • Introduction to Allergic Rhinitis (AR) • Subcutaneous Immunotherapy (SCIT) • Sublingual Immunotherapy Tablet (SLIT-T) • Approach in Family Practice
    51. 51. When to Refer AR to an Allergist • Symptoms of AR that are not adequately responding to medical therapy • Patient or referring physician would like to identify allergic triggers for proper allergen avoidance • Patient is having side effects to medical therapy or does not wish to take medical therapy • Consideration by the patient and/or family physician of immunotherapy to treat AR
    52. 52. AR Guidelines LTRAs: leukotriene receptor antagonsists *Step up if there is no response or incomplete response to treatment, regardless of class †LTRAs may be used in class III and IV, but there is less supporting evidence **Oral steroids may be considered for class II (severe intermittent), but there is little supporting evidence * Class I Class II Class III Class IV Allergen / irritant avoidance Oral H1 antihistamines Intranasal corticosteroids LRTAs† Oral steroids Immunotherapy Surgery Adapted from: Small P, et al. J Otolaryngol 2007; 36 (Suppl 1):S5-S27.
    53. 53. Simplified AR Treatment Algorithm Small and Kim. AACI Nov 2011. Treatments can be used individually or in any combination Allergen avoidance Allergen immunotherapy Oral antihistamines Leukotriene receptor antagonists Intranasal corticosteroids
    54. 54. Questions to ask patient for AR • Do you have nasal congestion, runniness and/or sneezing? • Do you have itchy, red and/or watery eyes? • Are your symptoms impacting your daily activities or sleep? • Do your symptoms change over the year and are they seasonal? • Have antihistamines and/or prescription nasal sprays been effective? Have they been used consistently and had an adequate trial?
    55. 55. Approach to AR in your Office • History should suggest AR • Look for associated issues such as atopic dermatitis, asthma, family history • Consider trial of non-sedating antihistamines, intranasal corticosteroids • Specific allergen-avoidance suggestions should be based on proper allergy-testing results • Consider referral
    56. 56. AR: Key Messages • AR is linked with asthma and conjunctivitis • Allergen skin tests are the best diagnostic test to confirm AR • Intranasal corticosteroids are the mainstay of treatment for most patients that present to physicians with AR • Allergen immunotherapy is an effective immune-modulating treatment that should be recommended if pharmacologic therapy for AR is not effective or is not tolerated Small and Kim. AACI Nov 2011.
    57. 57. Immunotherapy Conclusions • AR is common • SCIT is effective in the treatment of AR • SLIT-T is a new, effective treatment option in AR – demonstrated safety – suitable for pediatric use – administered at home
    58. 58. Case Study 1: Patient Presentation • 45-year-old female works in office as VP of software company • SAR for 12 years from spring to fall – symptoms are most bothersome in June now • She has some benefit with INS and antihistamines • No current medical problems or medications • She would like to try immunotherapy
    59. 59. Case Study 1: Discussion • Consider referral to allergist • Patient likely has grass as her major allergen • If SLIT-T is being considered, patient should be seen by allergist in December or earlier to arrange SLIT-T therapy for January preceding the next grass pollen season
    60. 60. Case Study 2: Patient Presentation • 27-year-old male • Allergies to grass and dust mites • Last injection one week ago • Regular build-up dose today (third injection into the final vial of pollen immunotherapy) • Within minutes, felt unwell, chest pain, groggy • Treated in clinic for anaphylaxis
    61. 61. Case Study 2: Discussion • Management of anaphylaxis in family practice • After a reaction to immunotherapy, should immunotherapy be continued? • How would this patient be managed if he wants to stop SCIT? • How would this patient be managed if he wants to continue SCIT?
    62. 62. Case Study 3: Patient Presentation • 12-year-old boy • Two-year history of severe rhinitis and conjunctivitis from May to July • Missed 10 days of school • Not better with INS or antihistamines • Skin test positive to grass • Parents would like to start immunotherapy
    63. 63. Case Study 3: Discussion • If a patient presents to you during the time of severe symptoms, what are some treatment options? • What are the options for further testing? • When would you refer this patient?
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