Background The house dust mite (HDM) sublingual immunotherapy (SLIT) tablet (MK-8237; Merck & Co, Kenilworth, NJ/ALK-Abelló, Hørsholm, Denmark) has demonstrated beneficial effects on allergic ...rhinoconjunctivitis and asthma outcomes in European trials. Objective This is the first trial to assess the efficacy/safety of HDM SLIT-tablets in North American subjects with HDM-induced allergic rhinitis with or without conjunctivitis (AR/C). Methods In this double-blind, multicenter trial (NCT01700192) 1482 subjects (aged ≥12 years) with HDM-induced AR/C with or without asthma were randomized to a daily SQ HDM SLIT-tablet (12 SQ-HDM dose) or placebo for up to approximately 52 weeks. A rhinitis daily symptom score (DSS; 4 nasal symptoms, maximum score = 12) of 6 or greater, or 5 or greater with 1 symptom being severe, on 5 of 7 consecutive days before randomization was required. The primary end point was the average total combined rhinitis score, which was defined as the rhinitis DSS plus rhinitis daily medication score (DMS), during the last 8 treatment weeks. Results Treatment with 12 SQ-HDM improved the total combined rhinitis score by 17% (95% CI, 10% to 25%) versus placebo. Improvements versus placebo in the secondary end points of average rhinitis DSS, rhinitis DMS, total combined rhinoconjunctivitis score, and visual analog scale–assessed AR/C symptoms were 16%, 18%, 17%, and 16%, respectively. All nominal P values were less than .001 versus placebo, except rhinitis DMS ( P = 0.15). No treatment-related adverse events meeting the International Council on Harmonization definition of a serious adverse event were reported; 1 nonserious treatment-related systemic allergic reaction occurred (assessed as moderate intensity) at first administration under medical supervision and was treated with epinephrine. Conclusions In the first North American trial of use of a SLIT-tablet for HDM allergy, 12 SQ-HDM was well tolerated and improved HDM-induced rhinitis symptoms in adults and adolescents.
How to use antihistamines Chu, Derek K; Oykhman, Paul; Sussman, Gordon L
Canadian Medical Association journal (CMAJ),
2021-Apr-06, 2021-04-06, 20210406, Volume:
193, Issue:
14
Journal Article
Peer reviewed
Open access
Chu et al offer tips on how to use antihistamines. Antihistamine use is most strongly supported for treating allergic rhinoconjunctivitis ("hay fever") and urticaria (hives). Avoid off-label usage ...for conditions where antihistamines have questionable utility, such as in managing asthma, eczema, cough or insomnia. First-generation antihistamines cause sedation, injury and impairment in sleep, and psychomotor and cognitive function, including impairing performance at school. Overdose can result in death from anticholinergic and anti-α-adrenergic effects, and QT prolongation. Systematic reviews of observational studies show no association with adverse fetal or maternal outcomes with antihistamine use during pregnancy or breastfeeding, and they are also safe for children. There is inadequate evidence regarding the newest antihistamines (rupatadine, bilastine) to support their use in pregnancy.
Utilisation appropriée des antihistaminiques Chu, Derek K.; Oykhman, Paul; Sussman, Gordon L.
Canadian Medical Association journal (CMAJ),
06/2021, Volume:
193, Issue:
25
Journal Article
Utilisation appropriee des antihistaminiques Chu, Derek K; Oykhman, Paul; Sussman, Gordon L
Canadian Medical Association journal (CMAJ),
06/2021, Volume:
193, Issue:
25
Journal Article
Background
Autoimmune chronic spontaneous urticaria (aiCSU) is an important subtype of chronic spontaneous urticaria (CSU) in which functional IgG autoantibodies to IgE or its high‐affinity receptor ...(FcεRI) induces mast cell degranulation and subsequent symptom development. However, it has not been tightly characterized. This study aimed to better define the clinical and immunological features and to explore potential biomarkers of aiCSU.
Methods
This was a multinational, multicenter study of 182 CSU patients. The clinical features studied included: urticaria activity and impact (UAS7 and quality of life); autologous serum skin test (ASST); IgG anti‐FcεRI and IgG anti‐IgE; IgG‐anti‐thyroperoxidase (IgG anti‐TPO); total serum IgE; and basophil reactivity (BASO) using the basophil activation test (BAT) and basophil histamine release assay (BHRA).
Results
Of the 182 patients, 107 (59%) were ASST+, 46 (25%) were BASO+, and 105 (58%) were IgG anti‐FcεRI+/IgE+. Fifteen patients (8%) fulfilled all three criteria of aiCSU. aiCSU patients appeared more severe (UAS7 21 vs 9 P < 0.016) but showed no other clinical or demographic differences from non‐aiCSU patients. aiCSU patients also had markedly lower total IgE levels (P < 0.0001) and higher IgG anti‐TPO levels (P < 0.001). Of biomarkers, positive BAT and BHRA tests were 69% and 88% predictive of aiCSU, respectively.
Conclusions
aiCSU is a relatively small but immunologically distinct subtype of CSU that cannot be identified by routine clinical parameters. Inclusion of BHRA or BAT in the diagnostic workup of CSU patients may aid identification of aiCSU patients, who may have a different prognosis and benefit from specific management.
Autoimmune chronic spontaneous urticaria (aiCSU) is defined by IgG anti‐IgE or FcεRI, a positive basophil activation test (BAT) and a positive autologous serum skin test (ASST). 14% of ASST+ patients have aiCSU with low IgE levels and elevated levels of anti‐thyroperoxidase. Positive BAT and basophil histamine release assays (BHRA) were 69% and 88% predictive of aiCSU and, therefore, are biomarkers.
Epicutaneous immunotherapy may have potential for treating peanut allergy but has been assessed only in preclinical and early human trials.
To determine the optimal dose, adverse events (AEs), and ...efficacy of a peanut patch for peanut allergy treatment.
Phase 2b double-blind, placebo-controlled, dose-ranging trial of a peanut patch in peanut-allergic patients (6-55 years) from 22 centers, with a 2-year, open-label extension (July 31, 2012-July 31, 2014; extension completed September 29, 2016). Patients (n = 221) had peanut sensitivity and positive double-blind, placebo-controlled food challenges to an eliciting dose of 300 mg or less of peanut protein.
Randomly assigned patients (1:1:1:1) received an epicutaneous peanut patch containing 50 μg (n = 53), 100 μg (n = 56), or 250 μg (n = 56) of peanut protein or a placebo patch (n = 56). Following daily patch application for 12 months, patients underwent a double-blind, placebo-controlled food challenge to establish changes in eliciting dose.
The primary efficacy end point was percentage of treatment responders (eliciting dose: ≥10-times increase and/or reaching ≥1000 mg of peanut protein) in each group vs placebo patch after 12 months. Secondary end points included percentage of responders by age strata and treatment-emergent adverse events (TEAEs).
Of 221 patients randomized (median age, 11 years quartile 1, quartile 3: 8, 16; 37.6% female), 93.7% completed the trial. A significant absolute difference in response rates was observed at month 12 between the 250-μg (n = 28; 50.0%) and placebo (n = 14; 25.0%) patches (difference, 25.0%; 95% CI, 7.7%-42.3%; P = .01). No significant difference was seen between the placebo patch vs the 100-μg patch. Because of statistical testing hierarchical rules, the 50-μg patch was not compared with placebo. Interaction by age group was only significant for the 250-μg patch (P = .04). In the 6- to 11-year stratum, the response rate difference between the 250-μg (n = 15; 53.6%) and placebo (n = 6; 19.4%) patches was 34.2% (95% CI, 11.1%-57.3%; P = .008); adolescents/adults showed no difference between the 250-μg (n = 13; 46.4%) and placebo (n = 8; 32.0%) patches: 14.4% (95% CI, -11.6% to 40.4%; P = .40). No dose-related serious AEs were observed. The percentage of patients with 1 or more TEAEs (largely local skin reactions) was similar across all groups in year 1: 50-μg patch = 100%, 100-μg patch = 98.2%, 250-μg patch = 100%, and placebo patch = 92.9%. The overall median adherence was 97.6% after 1 year; the dropout rate for treatment-related AEs was 0.9%.
In this dose-ranging trial of peanut-allergic patients, the 250-μg peanut patch resulted in significant treatment response vs placebo patch following 12 months of therapy. These findings warrant a phase 3 trial.
clinicaltrials.gov Identifier: NCT01675882.
The PEPITES (Peanut EPIT Efficacy and Safety) trial, a 12-month randomized controlled study of children with peanut allergy and 4 to 11 years old, previously reported the safety and efficacy of ...epicutaneous immunotherapy (EPIT) for peanut allergy (250 μg, daily epicutaneous peanut protein; DBV712 250 μg).
We sought to assess interim safety and efficacy of an additional 2 years of EPIT from the ongoing (5-year treatment) PEOPLE (PEPITES Open-Label Extension) study.
Subjects who completed PEPITES were offered enrollment in PEOPLE. Following an additional 2 years of daily DBV712 250 μg, subjects who had received DBV712 250 μg in PEPITES underwent month-36 double-blind, placebo-controlled food challenge with an optional month-38 sustained unresponsiveness assessment.
Of 213 eligible subjects who had received DBV712 250 μg in PEPITES, 198 (93%) entered PEOPLE, of whom 141 (71%) had assessable double-blind, placebo-controlled food challenge at month 36. At month 36, 51.8% of subjects (73 of 141) reached an eliciting dose of ≥1000 mg, compared with 40.4% (57 of 141) at month 12; 75.9% (107 of 141) demonstrated increased eliciting dose compared with baseline; and 13.5% (19 of 141) tolerated the full double-blind, placebo-controlled food challenge of 5444 mg. Median cumulative reactive dose increased from 144 to 944 mg. Eighteen subjects underwent an optional sustained unresponsiveness assessment; 14 of those (77.8%) maintained an eliciting dose of ≥1000 mg at month 38. Local patch-site skin reactions were common but decreased over time. There was no treatment-related epinephrine use in years 2 or 3. Compliance was high (96.9%), and withdrawals due to treatment-related adverse events were low (1%).
These results demonstrate that daily EPIT treatment for peanut allergy beyond 1 year leads to continued response from a well-tolerated, simple-to-use regimen.
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