Safety of Epicutaneous Immunotherapy in Peanut-Allergic Children: REALISE Randomized Clinical Trial Results.

BACKGROUND: Treatment options for peanut allergy are limited. In previous clinical trials, epicutaneous immunotherapy with a patch containing 250-µg peanut protein (Viaskin Peanut 250 µg [VP250]) was well tolerated and statistically superior to placebo in desensitizing peanut-allergic children. OBJECTIVE: To examine the safety of VP250 in children, using a study design approximating potential real-world use. METHODS: REAL LIfe Use and Safety of EPIT (REALISE) is a phase 3 multicenter study consisting of a 6-month, randomized, double-blind, placebo-controlled period followed by open-label active treatment. Children aged 4 to 11 years with physician diagnosis of peanut allergy received daily treatment with placebo (6 months) or VP250 (up to 36 months). Data from the 6-month, randomized, controlled phase of REALISE are reported. RESULTS: Three hundred ninety-three children were randomized 3:1 to receive VP250 (n = 294) or placebo (n = 99) for 6 months; 284 (72.3%) children had a history of peanut anaphylaxis. According to parent diary, all participants receiving VP250 and 83.8% receiving placebo reported at least 1 episode of local skin reaction, with frequency decreasing over time. Only 4 participants (1.4%) receiving VP250 discontinued because of adverse events (AEs). Epinephrine was administered for allergic reactions attributed to VP250 in 7 children (2.4%), of whom 5 remained in the study; none involved severe anaphylaxis. Overall, AE rates were similar among participants with and without a history of peanut anaphylaxis. CONCLUSIONS: In a study designed to mirror real-world use, VP250 was observed to be well tolerated in peanut-allergic children, consistent with previous phase 2b and 3 studies.

AR101 Oral Immunotherapy for Peanut Allergy.

BACKGROUND: Peanut allergy, for which there are no approved treatment options, affects patients who are at risk for unpredictable and occasionally life-threatening allergic reactions. METHODS: In a phase 3 trial, we screened participants 4 to 55 years of age with peanut allergy for allergic dose-limiting symptoms at a challenge dose of 100 mg or less of peanut protein (approximately one third of a peanut kernel) in a double-blind, placebo-controlled food challenge. Participants with an allergic response were randomly assigned, in a 3:1 ratio, to receive AR101 (a peanut-derived investigational biologic oral immunotherapy drug) or placebo in an escalating-dose program. Participants who completed the regimen (i.e., received 300 mg per day of the maintenance regimen for approximately 24 weeks) underwent a double-blind, placebo-controlled food challenge at trial exit. The primary efficacy end point was the proportion of participants 4 to 17 years of age who could ingest a challenge dose of 600 mg or more, without dose-limiting symptoms. RESULTS: Of the 551 participants who received AR101 or placebo, 496 were 4 to 17 years of age; of these, 250 of 372 participants (67.2%) who received active treatment, as compared with 5 of 124 participants (4.0%) who received placebo, were able to ingest a dose of 600 mg or more of peanut protein, without dose-limiting symptoms, at the exit food challenge (difference, 63.2 percentage points; 95% confidence interval, 53.0 to 73.3; P<0.001). During the exit food challenge, the maximum severity of symptoms was moderate in 25% of the participants in the active-drug group and 59% of those in the placebo group and severe in 5% and 11%, respectively. Adverse events during the intervention period affected more than 95% of the participants 4 to 17 years of age. A total of 34.7% of the participants in the active-drug group had mild events, as compared with 50.0% of those in the placebo group; 59.7% and 44.4% of the participants, respectively, had events that were graded as moderate, and 4.3% and 0.8%, respectively, had events that were graded as severe. Efficacy was not shown in the participants 18 years of age or older. CONCLUSIONS: In this phase 3 trial of oral immunotherapy in children and adolescents who were highly allergic to peanut, treatment with AR101 resulted in higher doses of peanut protein that could be ingested without dose-limiting symptoms and in lower symptom severity during peanut exposure at the exit food challenge than placebo. (Funded by Aimmune Therapeutics; PALISADE ClinicalTrials.gov number, NCT02635776 .).

Fluticasone furoate nasal spray is effective and well tolerated for perennial allergic rhinitis in adolescents and adults.

BACKGROUND: Fluticasone furoate nasal spray (FFNS), an intranasal corticosteroid, has been shown to be effective in perennial allergic rhinitis in randomized, double-blind, placebo-controlled studies but has been less extensively studied in perennial allergic rhinitis than seasonal allergic rhinitis. This study was designed to evaluate the efficacy and safety of FFNS in perennial allergic rhinitis in adolescents and adults ≥12 years of age. METHODS: In this randomized, double-blind, placebo-controlled, parallel-group study (FFU111439), patients ≥12 years old with perennial allergic rhinitis received FFNS, 110 micrograms (n = 160), or placebo (n = 155) q.d. for 4 weeks. RESULTS: Over the entire treatment period, FFNS was significantly (p < 0.05) more effective than placebo with respect to mean changes from baseline in daily reflective total nasal symptoms (primary end point), morning and evening reflective total nasal symptoms, daily reflective individual nasal symptoms, morning predose instantaneous total and individual nasal symptoms, and morning and evening peak nasal inspiratory flow. FFNS did not show a statistically significant difference from placebo in comparisons of ocular symptom measures. Clinically meaningful improvement versus placebo was observed on the Rhinoconjunctivitis Quality of Life Questionnaire with Standardised Activities overall score. Adverse events reported in >3% of patients in a treatment group and reported more frequently with FFNS than placebo were epistaxis (15% FFNS, 8% placebo) and nasopharyngitis (5% FFNS, 1% placebo). CONCLUSION: Once-daily FFNS was well tolerated and more effective than placebo at improving nasal symptoms of perennial allergic rhinitis in adolescents and adults ≥12 years of age.

Efficacy of a novel air filtration pillow for avoidance of perennial allergens in symptomatic adults.

BACKGROUND: Nighttime allergen exposures are a primary contributor to the development of allergic and asthmatic morbidities. Disease management guidelines recommend the use of environmental control measures to reduce these exposures, but clinically relevant reductions are difficult to achieve because most measures control only 1 allergen source among many in the bedroom environment. OBJECTIVE: To determine whether a novel localized approach to nighttime allergen avoidance provides effective exposure reductions and clinical benefits. METHODS: Thirty-five adults with perennial allergic rhinoconjunctivitis (dog, cat, or dust mite sensitivity) were randomized to receive PureZone, a combination therapy involving localized air filtration and pillow encasement, or placebo in a crossover trial with two 2-week treatment periods separated by a 1-week washout. Nasal and ocular allergy symptoms, quality of life, and breathing zone particulate exposure were assessed. Bedroom allergen dust samples were collected in the sleeping environment. RESULTS: Reductions (>99.99%) in allergen-sized particulate (> or = 0.3 microm) in the breathing zone led to significant improvements in nocturnal nasal and ocular allergy symptoms (P < .001) and quality of life (P = .02) for the active vs placebo device. Significant nocturnal symptom reductions vs placebo occurred the second night of use and were maintained for the duration of treatment; these reductions improved sleep problems in particular (P = .02). Allergens were detected in 100% of bedrooms, of which 44% had levels that exceeded sensitizing thresholds. CONCLUSIONS: The combination therapy of pillow encasement and localized air filtration provided effective nighttime allergen exposure reductions and clinical benefits without the use of adjunctive therapy.