Efficacy and safety of MK-7243: a grass allergy sublingual immunotherapy tablet evaluated in Canadian adults and children
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SUBMITTER: Hebert J
PROVIDER: S-EPMC4304021 | biostudies-literature | 2014 Jan
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:The effect of sublingual Timothy grass immunotherapy tablet 2800 BAU (grass SLIT-T) has been evaluated in three North American trials in adults and children who have allergic rhinitis with or without conjunctivitis (AR/C). This paper examines the effects of grass SLIT-T in Canadians. METHODS:Data for grass-allergic Canadians in three randomized, placebo-controlled, double-blind trials were analyzed post hoc: 1) adults ≥18 y, grass-pollen season [GPS] 2009; 2) children 5- <18 y, 2009; and 3) adults 18-65 y and children 5- <18 y, GPS 2012. Data from the GPS 2009 trials were pooled to provide a more precise estimate of treatment effects than the individual studies would provide. In every trial, participants received once-daily grass SLIT-T or placebo approximately 12 weeks before and continuing throughout the GPS. Participants used daily electronic diaries to record AR/C symptoms and medication use for treatment of symptoms. The therapeutic effect of grass SLIT-T was measured as a total combined score (TCS = daily symptom score + daily medication score) averaged over the entire GPS. Safety was assessed by monitoring adverse events (AEs). RESULTS:In the three trials, 386 Canadian participants were randomized; the overall population had 2284 participants. Canadian participants treated with grass SLIT-T in the pooled adult-pediatric 2009 trials showed a 38% mean TCS reduction relative to placebo (-2.06 difference [95% CI: -3.72, -0.39]; 3.32 vs. 5.37). Participants treated with grass SLIT-T in the adult-pediatric 2012 trial showed a 37% median TCS reduction relative to placebo (-1.53 difference [95% CI: -2.1, -0.3]; 2.58 vs. 4.11). Similar efficacy findings were observed over the peak GPS. Approximately 90% of treatment-related AEs were mild or moderate in severity. Two Canadian participants had moderate systemic allergic reactions (skin, respiratory, abdominal symptoms) to grass SLIT-T; symptoms resolved within 1 hour without medical intervention or treatment. No serious or life-threatening treatment-related AEs occurred. CONCLUSION:The 2800 BAU Timothy grass SLIT-T significantly improved AR/C induced by Timothy grass pollen in adults and children ≥5 y in Canadians, which was consistent with the robust efficacy observed in the overall trial population. The treatment was generally well tolerated. TRIAL REGISTRATION:Clinicaltrials.gov identifiers NCT00562159, NCT00550550, NCT01385371.
| S-EPMC4326370 | biostudies-literature
Project description: Not available
| S-EPMC4304079 | biostudies-literature
Project description:The majority of allergic patients are poly-sensitized. For causal treatment by allergy immunotherapy (AIT) a single or few allergen products containing the clinically most relevant allergens are applied, but few data on tolerability of multiple application of AIT is available. The aim of our study was to investigate safety and tolerability in patients who started treatment by sublingual immunotherapy (SLIT) with the standardised SQ(®) grass SLIT-tablet and were treated with concomitant AIT products.In a non-interventional, open-label, observational study in Germany treatment of patients with the SQ(®) grass SLIT-tablet and concomitant AIT (SCIT or SLIT) was documented between January 2012 and January 2014. Patients were followed at visits at first administration of the SQ(®) grass SLIT-tablet and after 1-3 months of treatment. Tolerability of the treatment with the SQ(®) grass SLIT-tablet and concomitant AIT were assessed by the physician and administration of AIT and adverse events (AEs) were recorded by the patients in diaries. AEs and adverse drug reactions (ADRs) were coded by using the Medical Dictionary for Regulatory Activities.In total, 181 patients were documented by 48 allergists and 160 patients treated with a concomitant AIT (SCIT 130, SLIT 30). AEs were reported in 58 (36.3 %) patients with concomitant AIT, and AEs considered related with the SQ(®) grass SLIT-tablet in 49 (30.6 %) and with concomitant AIT in 18 (11.3 %) patients. Treatment was discontinued due to ADRs in 12 (7.5 %) patients and severity of ADRs was assessed mild or moderate in 29 (18.1 %), and severe in 20 (12.5 %) patients. Most common reactions were localised at the application site of the SQ(®) grass SLIT-tablet as oral pruritus, throat irritation, oedema mouth and paraesthesia oral; no serious ADRs were reported. Overall tolerability of the SQ(®) grass SLIT-tablet if given with concomitant AIT was assessed as "good" or "very good" by 91.0 % of patients and 91.6 % of physicians.In comparison to data from previous studies no increase in frequency of AEs or change in the tolerability profile was observed when SLIT with the SQ(®) grass SLIT-tablet was administered with concomitant SCIT or SLIT.
| S-EPMC4782305 | biostudies-other
Project description:BackgroundAllergy immunotherapy (AIT), in the form of subcutaneous immunotherapy (SCIT) with alum-precipitated aqueous extracts, SCIT with a modified ragweed pollen allergen tyrosine adsorbate (MRPATA; Pollinex®-R), or a sublingual immunotherapy (SLIT)-tablet are options for the treatment of ragweed pollen allergic rhinoconjunctivitis (ARC) in Canadian children. A cost minimization analysis evaluated the economic implications of the use of the ragweed SLIT-tablet vs SCIT in Canadian children with ragweed ARC.MethodsA cost minimization analysis was conducted comparing the short ragweed SLIT-tablet, 12 Amb a 1-U, preseasonally with preseasonal ragweed SCIT, annual ragweed SCIT, or MRPATA. The analysis was conducted over a time horizon of 3 years from a public payer perspective in Ontario and Quebec. Resources and costs associated with medication and services of healthcare professionals were considered for each treatment. The resource and cost input values for the model were obtained from published literature and validated by Canadian clinical experts in active allergy practice. A discount rate of 1.5% was applied. Several scenario analyses were conducted to determine the impact of many of the key base case assumptions on the outcomes.ResultsOver the total 3-year time horizon, the ragweed SLIT-tablet had a potential cost savings of $900.14 in Ontario and $1023.14 in Quebec when compared with preseasonal ragweed SCIT, of $6613.22 in Ontario and $8750.64 in Quebec when compared with annual ragweed SCIT, and $79.62 in Ontario and $429.49 in Quebec when compared with MRPATA. The ragweed SLIT-tablet had higher drug costs compared with the other AIT options, but lower costs for healthcare professional services. The lower costs for healthcare professional services with the ragweed SLIT-tablet were driven by the need for fewer office visits than SCIT. Scenario analysis indicated that costs were most impacted by including societal costs (e.g., costs associated with patient/caregiver travel and time lost). The potential cost savings of the ragweed SLIT-tablet versus SCIT and MRPATA was maintained in most scenarios.ConclusionsIn this cost minimization analysis, the ragweed SLIT-tablet provided estimated cost savings from a public payer perspective for the treatment of ragweed ARC in Canadian children compared with SCIT or MRPATA.
| S-EPMC9847451 | biostudies-literature
Project description:BackgroundOral immunotherapy (OIT) and sublingual immunotherapy (SLIT) are potential therapies for food allergy, but the optimal method of administration, mechanism of action, and duration of response remain unknown.ObjectiveWe sought to explore the safety and efficacy of OIT and SLIT for the treatment of cow's milk (CM) allergy.MethodsWe randomized children with CM allergy to SLIT alone or SLIT followed by OIT. After screening double-blind, placebo-controlled food challenges and initial SLIT escalation, subjects either continued SLIT escalation to 7 mg daily or began OIT to either 1000 mg (the OITB group) or 2000 mg (the OITA group) of milk protein. They were challenged with 8 g of milk protein after 12 and 60 weeks of maintenance. If they passed the 60-week challenge, therapy was withdrawn, with challenges repeated 1 and 6 weeks later. Mechanistic correlates included end point titration skin prick testing and measurement of CM-specific IgE and IgG(4) levels, basophil histamine release, constitutive CD63 expression, CD203c expression, and intracellular spleen tyrosine kinase levels.ResultsThirty subjects with CM allergy aged 6 to 17 years were enrolled. After therapy, 1 of 10 subjects in the SLIT group, 6 of 10 subjects in the SLIT/OITB group, and 8 of 10 subjects in the OITA group passed the 8-g challenge (P = .002, SLIT vs OIT). After avoidance, 6 of 15 subjects (3 of 6 subjects in the OITB group and 3 of 8 subjects in the OITA group) regained reactivity, 2 after only 1 week. Although the overall reaction rate was similar, systemic reactions were more common during OIT than during SLIT. By the end of therapy, titrated CM skin prick test results and CD63 and CD203c expression decreased and CM-specific IgG(4) levels increased in all groups, whereas CM-specific IgE and spontaneous histamine release values decreased in only the OIT group.ConclusionOIT was more efficacious for desensitization to CM than SLIT alone but was accompanied by more systemic side effects. Clinical desensitization was lost in some cases within 1 week off therapy.
| S-EPMC3437605 | biostudies-literature
Project description: Not available
| S-EPMC4304081 | biostudies-literature
Project description:BackgroundCurrently accepted therapies for ragweed allergy in North America consist of pharmacotherapy and subcutaneous allergen immunotherapy injections to treat symptoms. Allergen immunotherapy not only reduces symptoms and the need for pharmacotherapy but has also been shown to have disease-modifying potential. Recently, ragweed immunotherapy administered via sublingual allergen tablet has been approved in North America for treatment of allergic rhinitis with and without conjunctivitis.MethodsThis was an analysis of pooled data for a prespecified subgroup of Canadian subjects from two multicentre, randomized, double-blind placebo-controlled trials of ragweed sublingual tablet (SLIT-T; 6 and 12 Amb a 1-U of Ambrosia artemisiifolia) in patients aged ≥18y, with ragweed-induced allergic rhinoconjunctivitis (AR/C) with or without asthma. Randomized subjects used once-daily ragweed SLIT-T or placebo for at least 12 weeks before the ragweed season and for up to 52 weeks post-randomization. The primary efficacy endpoint was the total combined score (TCS) based on the sum of AR/C daily symptom score (DSS) and daily medication score (DMS) averaged over the peak season. Treatment effects on TCS, DSS, and DMS in the entire season were also assessed. Adverse events (AEs) were monitored to assess safety.Results337 Canadian subjects were randomized in the two trials. During the peak season, ragweed SLIT-T 6 and 12 Amb a 1-U significantly reduced TCS by 26% (difference, -2.46 score point; p = .0009) and 40% (difference, -3.75 score point; p < .0001), respectively. In the overall population (N = 961), TCS reductions with 6 and 12 Amb a 1-U were 20% and 23%, respectively (both p < .001). Clinically meaningful reductions in entire-season TCS in Canadians were similar to those during peak ragweed season. Dose-dependent reduction of DSS and DMS was also observed for ragweed SLIT-T 6 and 12 Amb a 1-U during the peak season and the entire season. Ragweed SLIT-T was well tolerated in Canadian subjects and the overall population. Adverse events were generally mild to moderate and transient, occurring early in treatment; no systemic allergic reaction/anaphylaxis was noted.ConclusionRagweed SLIT-T is an effective form of immunotherapy that provides symptomatic efficacy of AR/C with a favorable risk profile in Canadian and overall populations.Trial registrationClinicaltrials.gov identifiers NCT00783198 and NCT00770315.
| S-EPMC4363352 | biostudies-literature
Project description: Not available
| S-EPMC4304026 | biostudies-literature
Project description:BackgroundDesign and execution of immunotherapy trials for seasonal allergies may be complicated by numerous factors including variable allergy testing methods, pollen levels, and timing and intensity of other seasonal allergens. We evaluated grass allergy immunotherapy tablet (AIT) treatment in North American adults with grass pollen-induced allergic rhinitis with or without conjunctivitis (AR/C), with/without asthma.MethodsSubjects age 18-65 with clinical history of grass pollen-induced AR/C, with/without asthma were randomized 1:1 to once-daily 2800 BAU Timothy grass AIT (oral lyophilisate, Phleum pratense, 75,000 SQ-T, containing approximately 15 μg of Phl p 5) or placebo. The AR/C symptom and medication scores were recorded daily. The primary end point was the average AR/C daily symptom score (DSS) during the entire grass pollen season (GPS). Ranked key secondary end points were Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score, daily medication score (DMS), and percentage of well days, all over entire GPS. Safety was monitored through adverse event reporting.ResultsEfficacy analysis included 289 subjects. Over the entire GPS, mean DSS was 6% lower with AIT versus placebo (5.69 vs. 6.06), but this difference was not statistically significant (p = 0.3475) despite significantly higher immunological response in the grass AIT group. No significant between-group differences were seen for key secondary end points. In general, DSS was high before GPS began and no clear relationship between DSS and grass pollen counts was seen during GPS. In post hoc analysis of subjects with pre-seasonal DSS ≤3, mean DSS and DMS were both significantly lower with grass AIT versus placebo (27%; p = 0.0327 and 68%; p = 0.0060, respectively). In this subgroup a relationship between DSS and grass pollen counts was observed. Grass AIT was generally well tolerated, with no events of anaphylactic shock or respiratory compromise.ConclusionsIn this trial, 2800 BAU grass AIT did not demonstrate significant symptom improvement versus placebo. Lack of relationship between pollen count and symptom score in the study population, and post hoc findings among subjects with low pre-seasonal symptoms, suggest that the symptoms reported in this study were not primarily reflective of the effects of grass pollen exposure.Trial registrationNCT00421655.
| S-EPMC3689082 | biostudies-literature
Project description:BackgroundWe have developed a recombinant B cell epitope-based vaccine (BM32) for allergen-specific immunotherapy (AIT) of grass pollen allergy. The vaccine contains recombinant fusion proteins consisting of allergen-derived peptides and the hepatitis B surface protein domain preS as immunological carrier.MethodsWe conducted a randomized, double-blind, placebo-controlled AIT study to determine safety, clinical efficacy and immunological mechanism of three subcutaneous injections of three BM32 doses adsorbed to aluminum hydroxide versus aluminum hydroxide (placebo) applied monthly to grass pollen allergic patients (n=70). Primary efficacy endpoint was the difference in total nasal symptom score (TNSS) through grass pollen chamber exposure before treatment and 4weeks after the last injection. Secondary clinical endpoints were total ocular symptom score (TOSS) and allergen-specific skin response evaluated by titrated skin prick testing (SPT) at the same time points. Treatment-related side effects were evaluated as safety endpoints. Changes in allergen-specific antibody, cellular and cytokine responses were measured in patients before and after treatment.ResultsSixty-eight patients completed the trial. TNSS significantly decreased with mean changes of -1.41 (BM32/20μg) (P=0.03) and -1.34 (BM32/40μg) (P=0.003) whereas mean changes in the BM32/10μg and placebo group were not significant. TOSS and SPT reactions showed a dose-dependent decrease. No systemic immediate type side effects were observed. Only few grade 1 systemic late phase reactions occurred in BM32 treated patients. The number of local injection site reactions was similar in actively and placebo-treated patients. BM32 induced highly significant allergen-specific IgG responses (P<0.0001) but no allergen-specific IgE. Allergen-induced basophil activation was reduced in BM32 treated patients and addition of therapy-induced IgG significantly suppressed T cell activation (P=0.0063).ConclusionThe B cell epitope-based recombinant grass pollen allergy vaccine BM32 is well tolerated and few doses are sufficient to suppress immediate allergic reactions as well as allergen-specific T cell responses via a selective induction of allergen-specific IgG antibodies. (ClinicalTrials.gov number, NCT01445002.).
| S-EPMC5049999 | biostudies-literature