May 2009
1) Dosing practical issues: build-up schedule, dose, dosing frequency and duration
a) What is the effective SLIT dosing range?
In a comprehensive review of SLIT studies published through October 2006, it was concluded that a consistent relationship between allergen dose and outcome had not been established.1 In this review, efficacy was demonstrated over a wide range of doses: ranging from 10 nanograms of Fel d 12 to 314 micrograms of Amb a 13, with the effective cumulative monthly SLIT dose being as high as 300 times the usual monthly subcutaneous (SCIT) maintenance dose. However, many of these same studies failed to demonstrate efficacy during the first year of treatment.
In contrast, many controlled SCIT studies using different allergens (dust mite4, ragweed5, cat6, 7, dog8, and timothy grass9) have demonstrated that the effective doses for SCIT are in the range of 5 to 20 micrograms of the major allergen.
Evidence of a SLIT dose-response relationship was suggested in one review that compared the relationship between SLIT dose, clinical efficacy, immunologic changes and improvement in provocation tests by pooling the results of studies published through October 2005 into four dosing categories.10 A clear relationship was found between higher relative dose, clinical efficacy and immunological changes (specific-IgG) but not with skin prick test or bronchial provocation.
Until recently, most of sublingual immunotherapy (SLIT) studies have involved relatively small numbers of subjects. In a review of published SLIT studies through January 2009 40 of the 58 double-blind, placebo-controlled studies had less than 100 subjects per study. Furthermore, 38/58 of these studies were of less than 12 months in duration.
In the past 3 years, several clinical trials investigating the efficacy of grass- pollen tablets have been conducted in large adult and pediatric populations. The trials demonstrated efficacy with the daily administration of grass pollen tablets from one of two different manufacturers (ALK-Abelló and Stallergenes) when using doses of 15 and 25 mcg of the group 5 major grass allergen, 11-14 For the Timothy grass tablet (Grazax®, ALK-Abelló, Denmark), three different doses (0.5 mcg, 5 mcg and 15 mcg of Phl p 5) were studied during one grass season. A clear dose-response relationship was demonstrated in symptom, rhinitis quality of life, and medication scores compared with placebo in the group that received the highest dose and at least 8 weeks of preseasonal treatment.13 A dose- response was also seen in the immunological markers studied (allergen specific-IgG & allergen specific-IgE "blocking antibody’) Subsequent studies demonstrated continued improvement in the second and third year.15 Another large dose-response study compared 3 doses of a 5-grass tablet (Oralair, Stallergènes, France), and found that 25mcg daily (300 IR) was the optimum dose in terms of safety and efficacy with the lower dose (100 IR) being no more effective than placebo.16 The higher dose (500 IR) was associated with more adverse effects and provided no greater clinical efficacy than the 300 IR group.
The demonstrated effective monthly maintenance dose of timothy grass administered subcutaneously is between 15 – 20 mcg Phl p 5.9, 17 Therefore, the demonstrated effective daily SLIT dose for timothy grass tablets is around the same dose given for SCIT monthly.
One tree pollen dose-response study in children with allergic rhinitis ± asthma who were randomized to receive either placebo or one of two cumulative weekly doses of major allergen, 30 mcg or 3.6 mcg, demonstrated a greater improvement in symptom and medication scores in the higher dose group.18 There was also a lower incidence of reported asthma symptoms in the higher dose group compared with the lower dose and placebo groups on a 2-year post-treatment telephone survey. Reported asthma symptoms at the 2-year follow-up correlated with the level of IL-5 mRNA expression at the end of treatment, with lower levels of IL-5 found in those that did not have signs of asthma.
For house dust mite and cat, the published data is conflicting, with high daily dosing being effective in some studies,19, 20 but not in others.21 In contrast, in some studies even very low doses seemed to be effective, e.g., 0.05 mcg of Fel d 1 daily with a cumulative yearly dose of 17 mcg, which is equivalent to a single SCIT maintenance dose.22
b) What is the dosing regimen used and how can these higher doses be achieved with SLIT?
The allergen extracts used in many of the SLIT studies were the same as the SCIT extracts (glycerol-saline solutions). Higher doses were achieved by using a concentrated solution or tablets and by administering the allergen extract more frequently. Many of the recent SLIT studies have used a daily maintenance-dosing regimen. There have been few studies that have compared SLIT dosing frequency regimens in humans. None of the studies compared the same dose administered at different dosing frequencies. All of the dosing-regimen studies compared more than one variable, which was usually dose and dosing frequency. One four-year study found daily dosing did better than 3 times a week.23 Another study comparing different dosing regimens showed conflicting results with better outcomes in the group that received treatment 3 times a week.21 However, this trial had several variables, different doses, dosing frequency, and timing of treatment in terms of the season (i.e. pre and co seasonal or co seasonal), which makes interpretation difficult. In both of these studies, the lowest cumulative dose was the most effective. One study compared three schedules, i.e. one drop given once, twice or three times a daily dosing. They found a significant reduction in medication use and skin test reactivity, compared with control group, only in the three times a day dosing group, which also received the higher dose.22
The SLIT up-dosing (build-up) regimens vary greatly. Many of the earlier studies utilized up-dosing regimens that ranged from 2 to 4 weeks. The dose would be increased by increasing the number of drops and the concentration of the allergen.
In the recent large trial using grass tablets, discussed earlier, no up-dosing or 2 day up-dosing schedules were used. There have also been several studies that utilized rush and “ultra-rush” (20 minute) protocols. Unlike SCIT, there does not appear to be a relationship with the type of induction schedule and frequency or severity of adverse reactions.
2) How does the efficacy of sublingual immunotherapy compare to injection Immunotherapy?
In a review of SLIT studies published before November 2005, 15/39 (38%) double-blind, placebo-controlled (DBPC) or randomized controlled (RC) studies that provided symptoms and mediation score for the primary disease studied demonstrated no efficacy in either parameter in the first treatment year.1 In the same review, 8 of the DBPC or RC studies, which had not demonstrated efficacy the first year, did demonstrate some efficacy in either symptoms, medication scores or both in the second or third year of treatment. In contrast, clinical improvement with SCIT, the standard to which SLIT is compared, may be demonstrated very shortly after the patient reaches the maintenance dose 9, 24-27 and the Allergen Immunotherapy: A Practice Parameter Second Update recommends considering discontinuing SCIT if clinical improvement is not apparent after one year of maintenance therapy.28
One double-blind, double-dummy, placebo-controlled study of SLIT vs. SCIT in birch allergic rhinitis patients found a greater magnitude of improvement in the SCIT group compared with the SLIT group; SLIT diminished the median symptom scores to one-half and SCIT to one-third when compared with placebo treatment.29 The difference between active treatment groups was not statistically significant, possibly due to the small number of patients completing the study i.e.1 4/23 SLIT, 19/24, SCIT, and 15/24 placebo. The small number of patients at completion may increase the risk of a type II statistical error, which is the failure to detect a treatment effect when one is actually present.
A comparison of two Cochrane meta-analysis of SLIT30 and SCIT31 for allergic rhinitis also found that the magnitude of improvement with SCIT may be greater than SLIT: 1) increased symptom reduction with SCIT [ standardized mean difference (SMD) of -0.73 (CI -0.97,-0.50)] compared with SLIT [SMD of -0.42 (CI -0.69, -0.15)] and 2) reduced use of medications with SCIT [SMD of -0.57 (CI -0.82,-0.33)] compared with SLIT [SMD of -0.43 (CI-0.63, -0.23)]
In a subsequent meta-analysis of 39 SLIT studies, the duration of SLIT in relation to its efficacy was evaluated.32 For studies with less than 1 year’s duration, the magnitude of effect of the treatment was low to moderate (SMD -0.31 for symptoms and -0.36 for medication score reduction). For studies with more than twelve months of treatment, the magnitude of effect was moderate to high (SMD -0.70 for symptoms and -0.44 for medication score reduction).
3) Can SLIT be used to treat polysensitized patients?
With the exception of one study33, there have been no SLIT studies that have specifically studied the efficacy of treating with more than one non-cross reacting allergen. This open-label, controlled study investigated the efficacy of combined birch and grass SLIT in comparison to single allergen SLIT or medications only in patients allergic to both allergens. Efficacy was seen during both the birch and grass season in patients who received both allergens. There was also improvement in clinical scores and nasal eosinophil counts scores in the patients treated with a single allergen compared with baseline and the untreated control group in both seasons (i.e., the target and unrelated pollen season). Proven efficacy of multi- allergen SLIT is important because most of the allergic US patients are sensitive to more than one allergen. In one US population-based survey (NHANES III) that involved skin testing of 10,863 people, the median number of positive skin test skin test was three.34 The number of positive skin test reactions is greater in the allergic rhinitis/asthma population. A recent study utilized data obtained from the Asthma Clinical Research Network to determine the relationship of aeroallergen sensitization to age, sex, ethnicity, and markers of inflammation and airways function. Percutaneous skin testing to 14 common aeroallergens was performed in 1338 subjects with objectively diagnosed mild-to-moderate asthma.35 Ninety-five percent of the subjects had at least 1 positive skin test response and 81% had positive reactions to 3 or more allergens.
Of note, many of the patients in the large SLIT clinical trials were polysensitized, which suggests that being sensitive to more than one allergen does not prevent a beneficial response to single allergen SLIT.36
4) How does the safety of SLIT compare to injection Immunotherapy?
One of the purported advantages of SLIT over SCIT is greater safety, which would allow for home administration. Adverse reactions do occur with oral-pharyngeal symptoms (pruritus, lip swelling, etc.) being relatively common during the build-up phase. In the double-blind, double-dummy study comparing SCIT with SLIT discussed in talking point 2, systemic reactions occurred in all three treatment groups. Using the 1993 EAACI classification the SLIT group had 15 grade 2 reactions and the SCIT group had 14 grade 2, 5 grade 3, and 1 grade 4 reactions.28
No fatalities have been reported with SLIT, but there have been several cases of anaphylaxis. Published studies include two cases (#1 & 2 below) which were associated with multi-allergen extracts, one case (# 3 below) associated with a latex rush protocol one case (#4 below) associated with a dose 6 times the usual maintenance after a 3 week gap in treatment, and. two additional cases (#5 & 6) described following the first dose of a grass tablet,
· 1) One occurred on the 3rd day of build-up with a multi-allergen SLIT extract in a 31 year old woman with allergic rhinitis and asthma37
· 2) One occurred with a mixed pollen at the height of pollen season one month after beginning maintenance in a 11 year old girl with allergic rhinitis and asthma after receiving 38
· 3) One occurred on the 4th day of a latex rush protocol; reaction described as “anaphylactic shock” 39
· 4) One occurred after a 3 week gap in maintenance treatment after taking a dose 6 times higher than prescribed dust mite SLIT (60 drops of 100 IR instead of 10 drops) in a 16-year-old girl with allergic rhinitis and asthma. She had 2 previous episodes of wheezing related to SLIT within the first 3 months of maintenance. This reaction resulted in loss of consciousness and admission to the intensive care unit.40
· 5 & 6) There have been two case reports of anaphylaxis with the first grass tablet dose in individuals who had to discontinue SCIT due to systemic reaction. 41 Both of these individuals had previously discontinued grass-pollen SCIT because of systemic reactions. One reaction was urticaria in a 13- year –old boy with allergic rhinitis, who developed periorbital angioedema and urticaria within 15 minutes of administering the grass tablet. The other case involved a 27-year-old woman with allergic rhinitis and asthma, who began to experience asthma symptoms, generalized itching, faintness and abdominal cramps immediately after the first grass tablet dose. She was wheezing and hypotensive (blood pressure 90/50) when she arrived in her general practitioner’s office, where she was treated with subcutaneous epinephrine.
One study has evaluated the systemic reaction rate in 43 patients who received 26 weeks of SLIT in a clinical practice.42 Five patients (11%) experienced 7 systemic reactions in 23,154 doses. All reactions were associated with wheezing or worsening of nasal symptoms. In addition, 1 patient had angioedema and urticaria. Six of the 43 patients had a history of a systemic reaction (SR) with previous SCIT treatment and 3 of these SCIT SR patients also had a SLIT SR. Due to the small population size, the authors could not determine if previous SCIT SR represented a significant risk factor for SLIT SR. The calculated systemic reaction rate was 11.6% of patients, and all were classified as grade 2 or 3 (the EAACI grading system).
Further studies in larger samples of patients are needed to determine if there are specific risk factors for SLIT. There have been no studies of SLIT to date in high-risk patients (e.g., severe asthma or patients who have had multiple severe systemic reactions with SCIT).
5) What about patient compliance with SLIT?
There have been a few studies specifically designed to assess patient compliance with SLIT using either unscheduled telephone requests to count remaining tablets or measuring remaining extract on clinic visits. They reported high compliance, which was defined as taking medications greater than 80 or 90 % of the time, in 70% to 97% of patients. 43-45
One study prospectively investigated compliance with three immunotherapy methods, SLIT, SCIT and nasal immunotherapy, in 2774 children by determining the number of patients who withdrew before completing 3 years of treatment.46 The highest noncompliance rate was seen in the nasal immunotherapy group (73.2% of patients) followed by SLIT (21.5% of patients) while SCIT (10.9 % of patients) had the lowest noncompliance rate.
6) Is it permissible to use the US licensed extracts for subcutaneous immunotherapy for SLIT, i.e. ‘off-label’ use?
The off-label use of products is not illegal. You are responsible for knowing the indications (on or off label) as well as the risks and benefits of any product you use in treatment of a patient. While pharmaceutical companies are prohibited by law from advertising off-label use of any of their products, physicians may use any FDA approved products for any indication she/he thinks appropriate. There should be published literature substantiating the off-label use indication. Use of approved medications off-label should also include a thorough risk/benefit/alternative discussion with the patient and documentation of the discussion and mutual decision to pursue treatment.
7) Do I need Informed Consent from a patient and/or their family, if I am providing off-label use of a medication? If so, what sort of information should be discussed during the informed consent process?
Yes – the patient must be informed of the off-label use of the medication and the reason for using this product off-label. As in any informed consent, all components of the informed consent must be provided to the patient including diagnosis, reason for use, risks, benefits, alternative therapies, risks if no treatment is provided, and probability of success. There should be a recording of the informed consent discussion. In a case such as SLIT, it is recommended that a patient sign the consent form as this is the best indication that the consent was obtained.
8) What type of instructions should be provided to patients receiving SLIT treatment?
One important factor to consider is that SLIT treatment is administered at home with no direct medical supervision. Physicians will need to provide specific instructions to the patients on how to administer the allergy extract, manage adverse reactions, prevent treatment interruptions, recognize situations in which the dose should be withheld, and manage dosing adjustments for any or all of these variables. Other considerations include whether injectable epinephrine should be routinely prescribed, the patient's ability to comply with the regimen and the patient’s response to a potential adverse reaction. The EAACI Immunotherapy Task Force recommended the following in their “Standards for Allergen-specific Immunotherapy”: 47
“The scientific documentation for treatment schedules and dose modifications is limited. For routine treatment, following the guidelines from the manufacturers is sensible.
• The administration of sublingual immunotherapy must be postponed in the following circumstances:
§ In the presence of oropharyngeal infection.
§ In the case of major dental surgery.
§ Acute gastroenteritis.
§ Exacerbation of the asthma.
§ PEFR <80% of personal best value.
§ Simultaneous administration of viral vaccines”
9) Can I get reimbursed for SLIT?
There is no FDA approved formulation and no CPT (billing code) for this therapy in the United States. An FDA approved SLIT formulation would be needed to apply for a new reimbursable CPT code. Medicare specifically states that it does not cover sublingual immunotherapy (see excerpt below). Most insurers would not reimburse for SLIT services, if there is no CPT code or FDA approved formulation. Therefore, the patient would need to personally pay for the costs associated with SLIT. Recently, BC/BS in the New England area submitted a request for a CPT code that would cover SLIT. They failed to get a single specialty society to support their request, which is a requirement before a new CPT code will be considered by the AMA. There is a one year ‘moratorium’ for reapplying for a new CPT code after a failed attempt.
Source: Page 14 of Medicare National Coverage Determinations Manual
Chapter 1, Part 2 (Sections 90 – 160.25) Coverage Determinations (Rev. 45, 12-06-05)110.9 – Antigens Prepared for Sublingual Administration (Rev. 1, 10-03-03)
CIM 45-28
For antigens provided to patients on or after November 17, 1996, Medicare does not cover such antigens if they are to be administered sublingually, i.e., by placing drops under the patient’s tongue. This kind of allergy therapy has not been proven to be safe and effective. Antigens are covered only if they are administered by injection.
10) How has the European market been impacted by the introduction of SLIT?
In parts of Europe, such as France and Italy, SLIT is the most commonly prescribed form of new immunotherapy. According to the financial reports of one of the largest allergen extract manufacturers in Europe, the SCIT market has continued to grow despite the increased use of SLIT.
11) Will SLIT be included in the practice parameters?
At the present SLIT is considered investigational in the United States and this is clearly stated in the current Allergen Immunotherapy Practice Parameter. 48 Specific practice parameters for SLIT will not be developed until there is an FDA approved formulation for SLIT.
12) What is the status of the US SLIT clinical trials?
Several companies are currently conducting clinical trials with tablet and solution SLIT. In addition, there are several investigator initiated SLIT trials. More information about the trials can be found on www.clinicaltrials.gov
A) Greer clinical trials
Phase 1: cat, dust mite, ragweed, grass-completed and results have been published 49
Phase IIb:
· Timothy grass: results never formally presented but per press release: “Greer reports low grass pollen levels appear to affect outcome of phase IIb clinical trial for sublingual-oral immunotherapy for timothy grass”
· Short ragweed-results presented as an abstract at the 2008 AAAAI Annual Meeting50
o Symptoms: approached statistical significance in high dose group: high dose: reduction of 0.81 (p = 0.051) but NS in medium dose: reduction of 0.54
o Medications: reduced in both SLIT groups but only statistically significant in the high dose (p<0.05)
o Immunologic parameters: Both SLIT groups showed an increase in ragweed-specific IgG and IgA
o Adverse events (AE): Greater frequency of oral-mucosal AEs in the SLIT groups vs. placebo. However, the overall rate of AEs did not significantly differ between groups. No severe AEs.
· Phase III: short ragweed-completed and results are being analyzed
B) ALK/Schering-Plough
Phase 1: ragweed-completed but never results never formally presented
Phase III: grass tablet: completed but results never formally presented but via press release: “ALK-Abelló's grass tablet US clinical study (GT-14) did not meet its primary endpoint. GT-14 study enrolled 329 patients and the majority of patients in the active and placebo arms did not record an increase in rhinoconjunctivitis symptoms during the grass pollen season, -as a result the trial did not meet its primary endpoint.”
C) Stallergenes
· Phase III: grass tablet-in progress
D) Planet Technology
· Phase II: cat, ragweed- in progress
E) Other studies: investigator-initiated
· Principle Investigator: Hal Nelson MD
Multi-allergen vs. single allergen: results of below study presented as an oral abstract at the AAAAI 2009 Annual Meeting51
Objectives: Efficacy of timothy SLIT (30 x SCIT) alone vs. in mixture of up to 9 additional allergen extracts, each at ~20 times the conventional SCIT dose
Efficacy parameter: symptoms during the grass pollen season after one year of SLIT compared with baseline observational year.
Objective parameters: titrated PST nasal challenges, timothy-specific serum IgA and IgG4 before and following one year of SLIT
Three treatment groups: daily for 1 year
1) SLIT with timothy pollen extract alone
2) SLIT with timothy pollen extract combined with up to 9 other extracts to which the subjects had + PST
3) SLIT of matching placebo.
Results:
o No significant difference in medication or symptom scores in the timothy alone and multi-allergen groups compared with placebo
o Perhaps due to very low grass pollen season 2008
o Significant improvement in titrated skin pick tests (tSPT), nasal challenge, increased timothy-specific IgG4, and decreased IFN-g levels in the timothy alone compared to placebo
o Significant improvement in tSPT in the multi-allergen group compared to placebo, although less than with timothy alone group
o There were significantly more adverse events in the active groups, timothy only (84%, p < 0.0001) and multi-allergen group (65%, p 5 0.0003), compared to placebo (6%).
Authors conclusions:
o The timothy alone arm shows that SLIT is effective with 17 mcg Phl p 5 daily for 10 months
o The multiallergen SLIT results raise serious concerns regarding its effectiveness
o The numbers are too small to be able to show differences between the active treatments but suggest that this question should be explored in appropriately powered studies before multiallergen SLIT is introduced in allergy practice
· Principle Investigator: NR Reschamwala, MD
Randomized Placebo-controlled SLIT Study on Safety of Dust Mite +Timothy combination SLIT52
Study design: 12 month study of adults and children with dust mite (DF) and timothy grass AR ± asthma: 5/08 to 9/09
Primary outcome: safety of combined therapy
Secondary outcomes: # of pts with 30% improvement over placebo in rhinoconjunctivitis grass pollen season & winter
Tertiary outcome: improvement in medication use & QOL
Clinical results will not be analyzed until available until 2010 but some preliminary results presented at the AAAAI 2009 Annual Meeting52
• Methods: Paired plasma samples from 5 patients were analyzed at start of therapy compared 2 months after dosing
• Results:
o Increase in tolerogenic markers including IL-10 (5.3 fold), and TGB beta (9.5 fold), and XCL1 (3:1 fold) in 3 of 5 subjects, after 2 months of dosing.
o Decreases were seen in IL-4, IL-13 and IL-9, inflammatory cytokines, by at least 4 fold.
• Conclusions: First double allergen SLIT trial to study specific T cell down regulation to allergens as well as non-specific tolerance markers. Clinical improvement will be assessed over the next 2 years.
• Principal Investigator: Robert K. Bush, MD
Immunotherapy Administered Under the Tongue to Treat Dust Mite Allergy
Sponsored by National Center for Complementary and Alternative Medicine
Study Design: Randomized, DBPC, Parallel Assignment, Safety/Efficacy
Results presented at AAAAI 2009 Annual Meeting as an oral abstract (safety)53 and late breaking abstract (efficacy)
• Methods: First PBDB trial of HDM SLIT in the U.S designed to evaluate safety & efficacy of high and low dose SLIT in adults with AR± asthma randomized to daily high (4200 AU) , low (60 AU) D. farinae SLIT (Greer,) or placebo (0.038 mg histamine, N=11) for 12-18 months.
• Efficacy outcomes: D. farinae-specific IgG4 levels & bronchial allergen challenge measured in asthmatics at baseline & end of study
• Results: High dose HDM SLIT resulted in a significant increase in HDM specific IgG4 and an increased HDM-bronchial challenge when compared to placebo.
– HDM-specific IgG4 ( p=0.02)
• Placebo (n=5) changed from 0.23+/-0.05 (mg/L/SEM) to 0.29+/-0.10
• High dose SLIT (n=9) changed from 0.20+/-0.03 to 0.54+/0.09
• HDM bronchial challenge( p=0.04) :
• Placebo (n=3) changed from 141+/-105 to 83+/-73.6 CBU
• High dose SLIT(n=7), 70+/-18.2 at baseline to 101+/-13.6 CBU
• Efficacy conclusions: High dose D. farinae SLIT induced a significant increase in HDM sIgG4 & antigen bronchial provocation
• Safety results: 21 completed (high N = 9, low= 7, placebo N=5)
– Withdrawals: 4/10 for possible treatment AE-1 in each treatment group (GI) & 2 in placebo (headache, ↑allergic sx)
– Possible treatment-related AEs in 15/21 who completed: GI symptoms & oral/throat irritation of mild to moderate severity (high dose N = 6, low dose = 4, placebo N = 5).
– No systemic reactions (urticaria, anaphylaxis) were observed in any group.
• Principle investigator: Robert Woods, MD
Sublingual Cockroach Safety Study: A Non-Randomized, Open Label, Uncontrolled Safety and Pilot Dosing Study for Sublingual-Oral Administration of Glycerinated German Cockroach Allergenic Extract in Pediatric and Adult Subjects With Cockroach Allergy and Perennial Allergic Rhinitis With or Without Asthma
Sponsored by National Institute of Allergy and Infectious Diseases
Results not presented
• Principle investigator: Wesley Burkes, MD
Peanut Sublingual Immunotherapy: 3 studies
Presented as a poster: Laubach et al., AAAAI 2008 Annual Meeting54
Immunotherapy for Peanut Allergy: Non-Randomized, Open Label, Active Control, Single Group Assignment, Efficacy Study:
Study design: Pilot evaluation of SLIT in peanut-allergic subjects aged 6 to 35 years. Dosage escalation to a maintenance dose of 22 mcg/day of peanut protein (14% Ara h 1, 6% Ara h 2) was continued for 18 months. Subjects
and their families completed daily home diaries. Immunologic laboratory
studies were performed at 0, 3, 6, 12, and 18 months.
RESULTS: 2/7 subjects had allergic symptoms on the initial desensitization day.
Three subjects experienced minimal allergic symptoms during the observed
dose escalations. The home diary reports document 75 episodes of
potential allergic symptoms following approximately 4070 home doses given (1.8%). The most common were sneezing, oral pruritus, and rhinorrhea (often associated with concurrent URI).
Immunological markers: IgE, IgG, and IgG4 levels and markers of basophil activation have not statistically changed over the first 12 months of SLIT.
Authors’ conclusions: “SLIT immunotherapy appears to be a well-tolerated form of peanut immunotherapy. Serum immunoglobulin levels have not changed significantly, which correlates with observations of SLIT for inhaled allergens. Static immunoglobulin and basophil data may be due to the low maintenance dose and food challenges will clarify the significance.”
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