Sublingual Immunotherapy Tablet Research Articles

Treatment with the SQ tree sublingual immunotherapy tablet is safe and well tolerated in real-life.

The SQ tree sublingual immunotherapy (SLIT)-tablet is authorised for treatment of allergic rhinoconjunctivitis with or without asthma in trees of the birch homologous group in 21 European countries. The primary objective of this study was to explore the safety in real-life. In a prospective, non-interventional post-authorisation safety study (EUPAS31470), adverse events (AEs) and adverse drug reactions (ADRs) at first administration and follow-up visits, symptoms, medication use, and pollen food syndrome were recorded by physicians in 6 European countries during the first 4-6months of treatment. ADRs with the SQ tree SLIT-tablet were reported in 57.7% of 1069 total patients (median age 36.0years, 53.7% female) during the entire observation period (severity, mild-to-moderate: 70.1%, severe: 4.7%, serious: 0.7%) and in 45.9% after first administration. ADRs were not increased with pollen exposure at first administration. With coadministration of the SQ tree and grass SLIT-tablet AEs were reported in 73.8% of patients and in 52.8% with the SQ tree SLIT-tabletalone. Nasal and eye symptoms improved in 86.9% and 80.9% of patients and use of symptomatic medication in 76.0%. PFS with symptoms was reported in 43.0% of patients at baseline and in 4.3% at the individual last visit. The results of this non-interventional safety study with the SQ tree SLIT-tablet confirm the safety profile from placebo-controlled clinical trials and support effectiveness in real-life according to the published efficacy data. Safety was not impaired by pollen exposure at first administration or co-administration with other SLIT-tablets.

SQ sublingual immunotherapy tablets for children with allergic rhinitis: A review of phase three trials.

To provide paediatricians with a summary of efficacy and safety of SQ sublingual immunotherapy (SLIT) tablets from phase three, randomised, double-blind, placebo-controlled trials in children and adolescents with allergic rhinitis or rhinoconjunctivitis, with and without asthma. PubMed searches were conducted and unpublished data were included if necessary. Of the 93 publications, 12 were identified reporting 10 trials. One trial was excluded as paediatric-specific efficacy data were unavailable. The nine eligible trials evaluated grass, house dust mite, ragweed and tree SLIT tablets. Consistent reductions in allergic rhinitis or rhinoconjunctivitis symptoms and medication use were observed with SQ SLIT tablets versus placebo. In a five-year trial, sustained reduction of allergic rhinoconjunctivitis symptoms, asthma symptoms and medication use were observed with SQ grass SLIT tablet versus placebo. The number-needed-to-treat to prevent asthma symptoms and medication use in one additional child during follow-up was lowest in younger children. SQ SLIT tablets were generally well tolerated across trials. Evidence supports use of SQ SLIT tablets in children and adolescents with allergic rhinitis or rhinoconjunctivitis, with and without asthma. Long-term data demonstrate disease-modifying effects of SQ grass SLIT tablet and suggest the clinical relevance of initiating allergy immunotherapy earlier in the disease course.

House dust mite sublingual allergen immunotherapy tablet is safe and well-tolerated in Dutch clinical practice.

Half (49%) of clinically diagnosed allergic rhinitis (AR) patients are sensitized to house dust mite (HDM). If allergen avoidance and symptomatic medication fail, allergen immunotherapy may be indicated. We investigated safety and tolerability of HDM-sublingual immunotherapy by HDM-SLIT tablets in Dutch daily clinical practice. Daily intake of 12 SQ-HDM SLIT-tablet was investigated in a prospective, multicenter, observational study (EUPAS43753). It comprised 4 consultations in 1 year. Data on safety, tolerability, treatment satisfaction, symptomatic medication, compliance, and clinical effectiveness (Control of Allergic Rhinitis and Asthma Test; CARAT) were collected. Descriptive and longitudinal regression data analysis were performed. Adult patients (n = 415), mean (SD) age 36.6 (12.2) years, 61.4% female and 36% asthmatic were included. The preponderance (65.1%) experienced adverse events (AEs). These, mostly mild (67%), AEs comprised: oral allergic reactions (58.6%), respiratory (12.4%) and gastrointestinal symptoms (9.4%). Sixty (14.5%) patients stopped due to AEs and 76 (18.3%) for non-AE reasons. CARAT scores improved clinically significant by 6 points and symptomatic medication use decreased from 96.1% to 77.4%. Most patients (74.5%) tolerated the treatment and were compliant (>86.5%). The majority of patients (62.4%) and investigators (69.4%) were satisfied with treatment. HDM SLIT-tablet is a safe and well-tolerated AR treatment. AEs occur often but are mostly mild and decreasing during the first year. CARAT scores improved and symptomatic medication use decreased suggesting better control of AR with treatment. Compliance, tolerability, and treatment satisfaction are good. However, patient follow-up and compliance remain important points of attention when initiating treatment.

Executive Summary of Clinical Practice Guideline on Immunotherapy for Inhalant Allergy.

Allergen immunotherapy (AIT) is the therapeutic exposure to an allergen or allergens selected by clinical assessment and allergy testing to decrease allergic symptoms and induce immunologic tolerance. Inhalant AITis administered to millions of patients for allergic rhinitis (AR) and allergic asthma (AA) and is most commonly delivered as subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT). Despite its widespread use, there is variability in the initiation and delivery of safe and effective immunotherapy, and there are opportunities for evidence-based recommendations for improved patient care. The purpose of this clinical practice guideline is to identify quality improvement opportunities and provide clinicians trustworthy, evidence-based recommendations regarding the management of inhaled allergies with immunotherapy. Specific goals of the guideline are to optimize patient care, promote safe and effective therapy, reduce unjustified variations in care, and reduce risk of harm. The target patients for the guideline are any individuals aged 5 years and older with AR, with or without AA, who are either candidates for immunotherapy or treated with immunotherapy for their inhalant allergies. The target audience is all clinicians involved in the administration of immunotherapy. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group. It is not intended to be a comprehensive, general guide regarding the management of inhaled allergies with immunotherapy. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients. The guideline development group made a strong recommendation that (Key Action Statement [KAS] 10) the clinician performing allergy skin testing or administering AIT must be able to diagnose and manage anaphylaxis. The guideline development group made recommendations for the following KASs: (KAS 1) Clinicians should offer or refer to a clinician who can offer immunotherapy for patients with AR with or without AA if their patients' symptoms are inadequately controlled with medical therapy, allergen avoidance, or both, or have a preference for immunomodulation. (KAS 2A) Clinicians should not initiate AIT for patients who are pregnant, have uncontrolled asthma, or are unable to tolerate injectable epinephrine. (KAS 3) Clinicians should evaluate the patient or refer the patient to a clinician who can evaluate for signs and symptoms of asthma before initiating AIT and for signs and symptoms of uncontrolled asthma before administering subsequent AIT. (KAS 4) Clinicians should educate patients who are immunotherapy candidates regarding the differences between SCIT and SLIT (aqueous and tablet) including risks, benefits, convenience, and costs. (KAS 5) Clinicians should educate patients about the potential benefits of AIT in (1) preventing new allergen sensitization, (2)reducing the risk of developing AA, and (3) altering the natural history of the disease with continued benefit after discontinuation of therapy. (KAS 6) Clinicians who administer SLIT to patients with seasonal AR should offer pre- and co-seasonal immunotherapy. (KAS 7) Clinicians prescribing AIT should limit treatment to only those clinically relevant allergens that correlate with the patient's history and are confirmed by testing. (KAS 9) Clinicians administering AIT should continue escalation or maintenance dosing when patients have local reactions to AIT. (KAS 11) Clinicians should avoid repeat allergy testing as an assessment of the efficacy of ongoing AIT unless there is a change in environmental exposures or a loss of control of symptoms. (KAS 12) For patients who are experiencing symptomatic control from AIT, clinicians should treat for a minimum duration of 3 years, with ongoing treatment duration based on patient response to treatment. The guideline development group offered the following KASs as options: (KAS 2B) Clinicians may choose not to initiate AIT for patients who use concomitant beta-blockers, have a history of anaphylaxis, have systemic immunosuppression, or have eosinophilic esophagitis (SLIT only). (KAS 8) Clinicians may treat polysensitized patients with a limited number of allergens.

Clinical Practice Guideline: Immunotherapy for Inhalant Allergy.

Allergen immunotherapy (AIT) is the therapeutic exposure to an allergen or allergens selected by clinical assessment and allergy testing to decrease allergic symptoms and induce immunologic tolerance. Inhalant AITis administered to millions of patients for allergic rhinitis (AR) and allergic asthma (AA) and is most commonly delivered as subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT). Despite its widespread use, there is variability in the initiation and delivery of safe and effective immunotherapy, and there are opportunities for evidence-based recommendations for improved patient care. The purpose of this clinical practice guideline (CPG) is to identify quality improvement opportunities and provide clinicians trustworthy, evidence-based recommendations regarding the management of inhaled allergies with immunotherapy. Specific goals of the guideline are to optimize patient care, promote safe and effective therapy, reduce unjustified variations in care, and reduce the risk of harm.The target patients for the guideline are any individuals aged 5 years and older with AR, with or without AA, who are either candidates for immunotherapy or treated with immunotherapy for their inhalant allergies. The target audience is all clinicians involved in the administration of immunotherapy. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group (GDG). It is not intended to be a comprehensive, general guide regarding the management of inhaled allergies with immunotherapy. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients. The GDG made a strong recommendation that (Key Action Statement [KAS] 10) the clinician performing allergy skin testing or administering AIT must be able to diagnose and manage anaphylaxis. The GDG made recommendations for the following KASs: (KAS 1) Clinicians should offer or refer to a clinician who can offer immunotherapy for patients with AR with or without AA if their patients'symptoms are inadequately controlled with medical therapy, allergen avoidance, or both, or have a preference for immunomodulation. (KAS 2A) Clinicians should not initiate AIT for patients who are pregnant, have uncontrolled asthma, or are unable to tolerate injectable epinephrine. (KAS 3) Clinicians should evaluate the patient or refer the patient to a clinician who can evaluate for signs and symptoms of asthma before initiating AIT and for signs and symptoms of uncontrolled asthma before administering subsequent AIT. (KAS 4) Clinicians should educate patients who are immunotherapy candidates regarding the differences between SCIT and SLIT (aqueous and tablet) including risks, benefits, convenience, and costs. (KAS 5) Clinicians should educate patients about the potential benefits of AIT in (1) preventing new allergen sensitizations, (2) reducing the risk of developing AA, and (3) altering the natural history of the disease with continued benefit after discontinuation of therapy. (KAS 6) Clinicians who administer SLIT to patients with seasonal AR should offer pre- and co-seasonal immunotherapy. (KAS 7) Clinicians prescribing AIT should limit treatment to only those clinically relevant allergens that correlate with the patient's history and are confirmed by testing. (KAS 9) Clinicians administering AIT should continue escalation or maintenance dosing when patients have local reactions (LRs) to AIT. (KAS 11) Clinicians should avoid repeat allergy testing as an assessment of the efficacy of ongoing AIT unless there is a change in environmental exposures or a loss of control of symptoms. (KAS 12) For patients who are experiencing symptomatic control from AIT, clinicians should treat for a minimum duration of 3 years, with ongoing treatment duration based on patient response to treatment. The GDG offered the following KASs as options: (KAS 2B) Clinicians may choose not to initiate AIT for patients who use concomitant beta-blockers, have a history of anaphylaxis, have systemic immunosuppression, or have eosinophilic esophagitis (SLIT only). (KAS 8) Clinicians may treat polysensitized patients with a limited number of allergens.

Epinephrine Administration in Sublingual Immunotherapy Tablet Trials is Rare in Children

Epinephrine Administration in Sublingual Immunotherapy Tablet Trials is Rare in Children

Modelling the impact of sublingual immunotherapy versus subcutaneous immunotherapy on patient travel time and CO2 emissions in Sweden

In Sweden, allergy immunotherapy (AIT) is available as either subcutaneous immunotherapy (SCIT) injections or sublingual immunotherapy (SLIT) tablets and is used to treat moderate-severe allergic rhinitis (AR). This study sought to determine treatment-related CO2 emissions and travel times in Swedish patients receiving either SCIT or SLIT-tablets. A list of specialized Swedish AR clinics that administer AIT was determined, and respective co-ordinates retrieved. Swedish municipality population data were obtained from a national database. The mean distance from each Swedish municipality to the nearest AR clinic was calculated, adjusted using a detour index, and weighted by estimated patient population size. Transport modality data were obtained from a Swedish urban transport study and CO2 emissions were obtained from Government sources. The mean number of annual SLIT-tablets and SCIT doses required were calculated based on product labels and clinical expert input. The annual number of healthcare professional interactions were layered into the model to estimate changes in mean patient travel time, distance, and travel-related CO2 emissions associated with using SCIT versus SLIT-tablets. Mean annual travel-related CO2 emissions were 410 tonnes (to two significant figures [s.f.]; standard deviation [SD] 90) with SLIT-tablets, versus 1700 tonnes (SD 380) for SCIT, resulting in mean annual savings of approximately 1300 tonnes (SD 290) of CO2 if all AIT patients were to receive SLIT-tablets instead of SCIT, over 380 times greater than 2021 average Swedish CO2 emissions per capita. Approximate mean annual travel times for patients taking SLIT-tablets were 66,500 h (three s.f.; SD 14,400), and 278,000 h (SD 60,200) for SCIT, resulting in mean annual savings of 211,000 h (SD 45,800) if all AIT patients were to receive SLIT-tablets instead of SCIT. Compared with SCIT injections, SLIT-tablets led to substantial reductions in treatment-related CO2 emissions and travel times for Swedish patients.

Consistent efficacy and safety of sublingual immunotherapy tablets across allergens and geographic regions.

The clinical development program of the SQ grass, ragweed, tree, and house dust mite (HDM) sublingual immunotherapy (SLIT)-tablets for allergicrhinitis/conjunctivitis (AR/C) included clinical trials conducted in North America,Europe, and Japan. Data from these trials were analyzed to assess efficacy, immunologic mechanisms, and safety outcomes acrossallergens and geographic regions. Thirteen phase III, double-blind, placebo controlled trials in the subjects with AR/C were conducted in NorthAmerica, Europe (including Russia), and Japan (N = 7763 analyzed). Trials were generally similar with respect to medicalpractice, target population, eligibility criteria, and efficacy and safety monitoring. Data were analyzed for the approved dosesin North America and Europe. Four statistical models were used to enhance comparison of the efficacy end points among the trials. The SLIT-tablets demonstrated consistent efficacy across allergens and regions, regardless of the statistical analysis used. Relative improvement in the primary efficacy end point compared with placebo by using the predefined protocol analysis ranged from 17.9% to 32.8%, 17.5% to 19.3%, 20.6% to 38.3%, and 39.6% with the grass, HDM, ragweed, and tree SLIT-tablets, respectively. The kinetics of specific immunoglobulin E (IgE) and IgG4 responses were similar among the allergensand regions. Local application-site reactions were the most common adverse events for all allergens and in all regions. Mosttreatment-related adverse events for all allergens and in all regions were mild in severity. The rate of systemic allergic reactions was similar across regions (0%-0.54%). Confirmatory phase III trials for SLIT-tablets in the treatment of AR/C showed consistent efficacy, immunologic,and safety outcomes across allergens and geographic regions.

Quantifying the benefits of early sublingual allergen immunotherapy tablet initiation in children.

Allergic rhinitis (AR) is a chronic inflammatory disease of the upper airway, which progresses into allergic asthma (AA) in up to 45% of children. This analysis aimed to investigate clinical and economic benefits of sublingual allergen immunotherapy (SLIT tablets) initiated early in childhood for the treatment of AR by quantifying the long-term reduction in new cases of AA. A Markov model was developed to estimate the long-term effects of SLIT tablets on the risk of developing asthma. Key parameters were primarily based on data from the GRAZAX® Asthma Prevention trial and included the age- and treatment-dependent risk of developing AA as well as annual probabilities of progression/remission in AR severity. Healthcare costs were estimated using data from the REACT study. In a modelled cohort of children with moderate-to-severe seasonal AR initiated on SLIT tablets at ages 7 and 12, 24% and 29%, respectively, develop AA during a 20-year period. In comparison, when initiated at age 5, 19% develop AA. Additionally, initiation of SLIT tablets at age 5 is associated with a total healthcare cost of EUR 20,429 per patient, whereas initiation at ages 7 and 12 is associated with, respectively, EUR 21,050 and EUR 22,379 per patient 20 years after AR diagnosis. Initiation of SLIT tablets in early childhood is associated with a clinically meaningful and permanent reduction in new cases of AA and lower healthcare costs among children with AR. This finding supports the clinical relevance of initiating SLIT tablets early for children with AR to obtain long-term clinical benefits.

Clinical benefits with 300 IR HDM SLIT tablet in Europeans with house dust mite allergic rhinitis: Post hoc analysis of a large phase 3 trial

BackgroundHouse dust mite (HDM)-induced allergic rhinitis (AR) is a major cause of allergic respiratory disease. The efficacy and safety of the 300 IR HDM sublingual immunotherapy (SLIT) tablet in patients with moderate-to-severe HDM-AR was confirmed in a large, international, phase 3 randomized controlled trials (RCTs). Here, we analyzed the results in the European population. MethodsData from 91 European centers that participated in the international, double-blind, RCT (EudraCT 2014-004223-46, NCT02443805) with the 300 IR HDM SLIT tablet versus placebo over 12 months were analyzed post hoc. The treatment effect in European adults and adolescents was notably assessed through the European Academy of Allergy and Clinical Immunology (EAACI)-recommended combined symptom and medication score (CSMS0-6, pre-defined endpoint) and the total combined rhinitis score (TCRS0-24, post hoc endpoint, also balanced) during the primary evaluation period (4 weeks at the end of treatment period) using analysis of covariance (ANCOVA). ResultsThere were 818 patients who comprised the modified full analysis set in Europe. Over the primary period, the differences in CSMS0-6 and TCRS0-24 between the 300 IR and placebo groups were statistically significant (p < 0.0001): −0.32 (95%CI [-0.46; −0.17]) and −1.28 (95%CI [-1.63; −0.94]), respectively, with relative differences of −20.9% and −21.2%. All post hoc and the rhinoconjunctivitis quality of life endpoints were significantly improved with 300 IR versus placebo. The 300 IR HDM tablet was generally well tolerated. ConclusionThis RCT sub-analysis confirmed the 300 IR HDM SLIT tablet is an effective and safe treatment for European adults and adolescents with HDM-AR with clinically meaningful benefits from the patients' perspective. Trial registrationNCT02443805. Registered on April 29, 2015./EudraCT 2014-004223-46. Registered on September 16, 2015.

Clinical relevance of pre- and coseasonal sublingual immunotherapy with a 300 index of reactivity 5-grass SLIT tablet in allergic rhinoconjunctivitis.

There is considerable interest in improving the scoring methods for evaluating the efficacy of allergen immunotherapy (AIT) and to show if this is associated with clinically meaningful results from the patient's perspective. We aimed to assess the efficacy and clinical relevance of a 300 index of reactivity (IR) 5-grass pollen sublingual immunotherapy (SLIT) tablet in children, adolescents and adults with moderate to severe grass-induced allergic rhinoconjunctivitis (ARC) with or without controlled asthma using the combined symptom and medication score CSMS0-36 . The data of the European population that participated in 3 Phase III, international, randomized double-blind placebo-controlled clinical trials were analyzed post hoc. A total of 864 patients randomized to 300 IR 5-grass tablet or placebo were analyzed. Over the primary evaluation period, the difference in CSMS0-36 between the 300 IR and placebo groups was statistically significant (point estimates: -2.51, CI95% [-3.88; -1.14], p<0.0001 in clinical trial1; -2.31, CI95% [-3.39; -1.23], p<0.0001 in CT2; and -2.31, CI95% [-3.58; -1.03], p=0.0004 in CT3). The relative differences between the 300 IR 5-grass tablet and placebo were -29.7%, -33.8%, and -26.3%, respectively. The results based on CSMS0-36 were consistent with those obtained with the primary endpoints of the trials and support the consideration of the 2-point threshold of the CSMS0-36 for clinical relevance of AIT. Post hoc analysis of 3 CTs with the 300 IR 5-grass SLIT tablet confirmed its significant and clinically relevant effect in the European population with grass pollen-induced ARC with or without controlled asthma.

Long-term health care resource and cost savings with allergy immunotherapy: REACT study results

Allergy immunotherapy (AIT) can be administered as subcutaneous immunotherapy (SCIT) injections in the clinic or as sublingual immunotherapy (SLIT) tablets at home after initiation under medical supervision. To achieve long-term, sustained effects, a 3-year treatment duration is recommended. Our aim was to assess the association of AIT (SCIT and SLIT tablets) with long-term health care resource use (HRU) and costs in subjects with allergic rhinitis. REACT was a retrospective propensity score-matched cohort study using claims data from a German health insurance database (2007-2017), with up to 9 years of follow-up after AIT initiation. HRU and costs were evaluated for hospitalizations, ambulatory care visits, and prescriptions, in subjects who received AIT versus in matched controls with allergic rhinitis who had not received AIT, as well as for SCIT and SLIT tablets. Across all 9 years, the subjects who received AIT had a significantly lower incidence of hospitalization than the controls did. Generally, proportions of subjects with ambulatory care visits and hospitalizations were lower, and length of hospitalization was shorter, for those receiving SLIT tablets than those who received SCIT. Total costs were significantly higher with AIT versus for the controls during the treatment period (years 1 to 3), driven by prescriptions and ambulatory care visits, but they were lower in years 4 to 9. During years 1 to 3, prescription costs were generally higher for SLIT tablets than for SCIT, whereas ambulatory care costs were numerically lower. In most years, hospitalization costs were numerically lower for SLIT tablets than for SCIT. Initial higher HRU and costs of AIT during the expected treatment period are offset in the long term. At-home administration of SLIT tablets may further reduce ambulatory care costs.

Anaphylaxis in Clinical Trials of Sublingual Immunotherapy Tablets

There is no consensus method to identify anaphylaxis in sublingual immunotherapy (SLIT) trials. Standardized Medical Dictionary for Regulatory Activities (MedDRA) queries (SMQs) are standardized groupings of MedDRA terms used in drug safety monitoring. To develop a method to identify potential anaphylaxis in SLIT-tablet trials using SMQ searches and case definitions of anaphylaxis adopted from the National Institute of Allergy and Infectious Disease. The SMQ search tool contained 2 criteria including treatment-emergent adverse events (AEs): (1) narrow MedDRA terms related to anaphylaxis and (2) all AEs with broad MedDRA terms from at least 2 of 3 categories (respiratory/skin/cardiovascular) occurring on the same day. Criteria were applied to a pooled data set of all subjects from 48 timothy grass, ragweed, house dust mite, and tree SLIT-tablet trials (SLIT-tablet, N= 8200; placebo, N= 7033). Additional search strategies were any treatment-emergent AE with MedDRA preferred term "hypersensitivity" and epinephrine administrations. Identified potential cases underwent blinded independent medical expert review. Nonanaphylaxis cases were designated local AEs or mild to moderate systemic reactions. Using the SMQ search tool and after subsequent medical review, 8 anaphylaxis cases were identified; 3 were considered treatment-related, resulting in a proportion of anaphylaxis cases/subject of 0.02% (2 of 8200) with SLIT-tablet and 0.01% (1 of 7033) with placebo. One additional anaphylaxis case related to SLIT-tablet was identified by the preferred term "hypersensitivity." The 3 anaphylaxis cases associated with SLIT-tablet treatment were not life-threatening. The epinephrine administration rate was 17 of 8200 (0.2%) with SLIT-tablet treatment and 2 of 7033 (0.03%) with placebo. SMQ search criteria for identifying potential anaphylaxis related to SLIT were developed. Anaphylaxis was rare for SLIT-tablets.

The Art of Immunotherapy

Selection of a patient with rhinitis/conjunctivitis or asthma for allergy immunotherapy (AIT) requires several decisions. First, does the patient's sensitization, pattern of exposure to an allergen, and degree of exposure to that allergen reasonably suggest a causal relationship? Does the level and duration of symptoms warrant the cost and inconvenience of immunotherapy, or is the patient motivated by the disease-modifying potential of AIT? If AIT is selected, is the choice to be greater safety and convenience with sublingual immunotherapy (SLIT) tablets, but with treatment probably limited to 2 or 3 allergens, or for subcutaneous immunotherapy where multiple allergen therapy is the rule and efficacy may be somewhat greater, at least initially, or does the physician go off-label into the unknowns of liquid SLIT? Are there extracts of sufficient potency to achieve likely effective doses? How does the physician deal with large local or systemic reactions, with gaps in treatment, with pollen seasons, and the use of premedication or cautionary prescription of epinephrine autoinjectors? How can adherence to AIT be improved? These and other questions are addressed in this paper.

SQ HDM sublingual immunotherapy tablet for the treatment of HDM allergic rhinitis and asthma improves subjective sleepiness and insomnia: an exploratory analysis of the real-life CARIOCA study.

There are still gaps in the knowledge regarding the effectiveness of house dust mite (HDM) sublingual immunotherapy (SLIT) on allergic rhinitis (AR) and asthma (AA)-associated sleep disorders. A non-interventional study was conducted to assess the effect of the Standardized quality (SQ) HDM SLIT-tablet on safety and symptoms in adults with HDM respiratory allergies. The aim was to describe the status of insomnia and daytime sleepiness in AR and/or AA patients treated with the SQ HDM SLIT-tablet. This was a 12-month multicenter, longitudinal and prospective study. Participants started the SQ HDM SLIT-tablet for moderate-to-severe HDM AR, persistent despite the use of symptom-relieving medication; or HDM AA not well controlled by inhaled corticosteroids and associated with mild-to-severe HDM AR. Sleep symptoms were measured using the Insomnia Severity Index (ISI) questionnaire and the Epworth Sleepiness Scale (ESS). A total of 1,526 adult patients were enrolled and 1,483 were included in the analysis. At baseline, 41.5% of patients reported sleep disorders: 77.0% of them had insomnia and 28.9% suffered from excessive daytime sleepiness. Insomnia was significantly more frequent among patients with uncontrolled AR (83.1%) than those with controlled AR (52.6%) (p<0.0001). Over time, 48.3% and 59.7% of patients reported an improvement greater than the minimal clinically important difference on the ISI and ESS scales respectively. In patients with HDM AR and/or asthma associated sleep disorders, an improvement in subjective insomnia and sleepiness was observed after one year of treatment with the SQ HDM SLIT-tablet in a real-life setting.

Extraction, Purification, and Development of Sublingual Film (SLIT Films) Comprising Cockroach Allergen for Treatment of Allergy.

Allergy associated with cockroaches are mostly from the American cockroach (Periplaneta americana) and German cockroach (Blattella germanica). The effective and safe treatment for cockroach allergy is Sublingual immunotherapy (SLIT). In this study, SLIT Films containing purified allergen extract of Periplaneta americana were prepared by solvent casting and were evaluated for their efficiency in delivery. Cockroach allergen extract was prepared and purified by ultrafiltration and chromatography. The molecular weight of protein content was identified and estimated by SDS- PAGE and ELISA. SLIT films were developed by the Quality by Design (QbD) approach and were evaluated for allergen- excipient compatibility, swelling index, taste, diffusion, in vitro dissolution, local toxicity, and stability analysis. Cockroach allergen protein extracts (cut-off 25-71KDa) were identified by SDS-PAGE and quantified by indirect ELISA and further selected for sublingual film preparation. The indirect ELISA results show a higher optical density (OD) value compared to crude extract. The weight uniformity and thickness of the film were between 13-18 mg and 0.04-0.06 mm. The disintegration time was found to be less than 1 min. The cumulative percentage release was also found to be satisfactory. The local toxicity study indicated no signs of irritation in the buccal mucosa of rabbits. The optimised F3 film had uniform thickness, faster disintegration and drug content within pharmacopeial limits. Ex vivo study revealed better permeability with 90% release of allergen in 7 minutes. The formulation was also stable at room temperature during the study period. SLIT Film containing cockroach allergen from Periplaneta americana was successfully developed and evaluated. SLIT films of cockroach allergen could be more beneficial and convenient for emergency use in patients when compared to subcutaneous immunotherapy. SLIT films provide dose accuracy and are a promising alternative for SCIT and SLIT drops and tablets.

The Art of Dosing for Subcutaneous Immunotherapy in North America

Subcutaneous immunotherapy (SCIT) is a long-established treatment option for allergic rhinoconjunctivitis. Proper dosing of the allergens is critical for the efficacy and safety of SCIT. Of the hundreds of liquid allergen extracts in the United States, effective and well-tolerated SCIT dosing has only been established for a small number. Thus, SCIT dosing remains largely empiric and continues to be, by necessity, an art. To highlight the complexity of SCIT dosing, this review summarizes the historical and current landscape of U.S. allergen extracts, differences among U.S. and European allergen extracts, allergen selection for SCIT, considerations for compounding of allergen extract mixtures, and recommended dosing. As of 2021, 18 standardized allergen extracts are available in the United States; all other extracts remain unstandardized without characterization of allergen content or potency. U.S. allergen extracts differ from European extracts in formulation and potency characterization. There is no standardized methodology for SCIT allergen selection, and interpretation of allergen sensitization is not straightforward. Compounding of SCIT mixtures requires consideration of potential dilution effects, allergen cross-reactivity, proteolytic activity, and additives. Probable effective dose ranges for SCIT are recommended in U.S. allergy immunotherapy practice parameters, although there are few studies using U.S. extracts supporting these doses as therapeutic. In contrast, optimized doses of sublingual immunotherapy tablets have been confirmed in North American phase 3 trials. The SCIT dosing for each patient remains an art that requires clinical experience and consideration of polysensitization, tolerability, compounding of allergen extract mixtures, and the range of recommended doses within the context of extract potency variability.

EE414 Health Economic Evaluation of Early Initiation of Grass Sublingual Immunotherapy Tablets in Children

Allergic rhinitis (AR) is recognized as a major risk factor for developing allergic asthma (AA). Previous research show childhood AR increases the risk of new-onset asthma two- to seven-fold. Having both AR and AA in childhood increases the risk of asthma persisting into adulthood. This study estimates costs and effectiveness for early initiation of 75,000 SQ-T grass SLIT-tablet, by quantifying the risk-reduction of new-onset of AA in children with moderate/severe AR.

Efficacy of Japanese cedar pollen sublingual immunotherapy tablets for Japanese cypress pollinosis.

We previously demonstrated the efficacy of Japanese cedar (JC) pollen sublingual immunotherapy (SLIT) tablets for treating seasonal allergic rhinitis in a clinical trial (trial no. 206-2-1) that covered 5 pollen dispersal seasons from 2015 to 2019. Our aim was to perform post hoc analysis of the 206-2-1 trial data to evaluate the efficacy of JC pollen SLIT tablets for patients with rhinitis induced by pollen from Japanese cypress (JCY), a related Cupressaceae species that has a pollen dispersal season overlapping with that of JC. Data were analyzed for 240 patients who received placebo during the first pollen dispersal season in 2015, were then rerandomized to receive JC SLIT tablets (the PA group) or placebo (the PP group) for 18 months (the 2016 and 2017 dispersal seasons), and were observed untreated for 2 years (the 2018 and 2019 dispersal seasons). The PA and PP groups were assigned to "high" and "low" subgroups if their rhinitis symptoms were exacerbated/did not change or decreased, respectively, during the peak JCY pollen dispersal period in 2015. The mean total nasal symptom and medication scores and other outcomes were compared for the high-PP, high-PA, low-PP, and low-PA groups during the 2016 to 2019 peak JCY pollen dispersal periods. The mean total nasal symptom and medication scores were significantly lower for the high-PA and low-PA groups than for the corresponding PP groups over the 4 years of treatment and observation. JCY pollen-specific IgE levels increased in both PA groups. JC pollen SLIT tablets effectively suppressed JCY pollinosis symptoms, supporting the clinical relevance of immunologic cross-reactivity between JC and JCY allergens.

House dust mite sublingual immunotherapy tablet safety in adolescents with allergic rhinoconjunctivitis: Worldwide clinical trial results

BackgroundThe house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet is a treatment option for allergic rhinitis with/without conjunctivitis (AR/C) approved in adults worldwide and in adolescents in some countries. ObjectiveTo supplement existing adolescent HDM SLIT-tablet safety data by conducting the MT-18 trial in adolescents. MethodsMT-18 (EudraCT:2020-000446-34) was a phase 3, open-label, single-arm, 28-day safety trial of daily HDM SLIT-tablet (12 SQ-HDM dose) in European adolescents (12-17 years) with HDM AR/C, with or without asthma. The primary end point was at least 1 treatment-emergent adverse event (TEAE). MT-18 results were compared with 12 SQ-HDM adolescent subpopulation data from previously described 1-year phase 3 trials conducted in North America (P001; clinicaltrials.gov:NCT01700192) or Japan (TO-203-3-2; JapicCTI:121848). ResultsNo treatment-related anaphylaxis, epinephrine administrations, severe local swellings, severe mouth or throat edema, or eosinophilic esophagitis occurred in the trials. For MT-18 (N = 253), P001 (N adolescents = 189), and TO-203-3-2 (N adolescents = 206), the percentage of adolescents treated with 12 SQ-HDM reporting any TEAE was 88%, 95%, and 93%, respectively, and the percentage reporting any treatment-related AE (TRAE) was 86%, 93%, and 66%, respectively. The most common TRAEs were local application site reactions. Most TRAEs were mild in intensity and were typically experienced the first 1 to 2 days of treatment. There were no asthma-related TEAEs with the HDM SLIT-tablet. The safety profile appears similar between adolescents with or without asthma at baseline. ConclusionThe HDM SLIT-tablet was well tolerated in European, North American, and Japanese adolescents with HDM AR/C, indicating safety of the HDM SLIT-tablet is insensitive to age or geographic region. Trial registrationClinicalTrials.gov Identifier: (P001: NCT01700192); EudraCT: (MT-18; 2020-000446-34); JapicCTI: (TO-203-3-2; 121848)