Assessment of long-term safety and efficacy of dupilumab in children with asthma (LIBERTY ASTHMA EXCURSION): an open-label extension study.

BACKGROUND: Dupilumab efficacy and safety in children aged 6-11 years with uncontrolled, moderate-to-severe asthma were shown in the VOYAGE study-a 52-week, multinational, multicentre, phase 3 randomised, double-blind, placebo-controlled trial. We aimed to evaluate the long-term safety and efficacy of dupilumab in children with moderate-to-severe asthma who previously participated in the VOYAGE study. METHODS: 365 of 408 children with moderate-to-severe asthma from VOYAGE enrolled in EXCURSION, a 52 week, open-label extension study conducted at 70 centres across 17 countries. 240 children continued with add-on dupilumab (dosed according to bodyweight: 100 mg for those weighing ≤30 kg and 200 mg for those weighing more than 30 kg at EXCURSION baseline) once every 2 weeks administered by subcutaneous injection (dupilumab/dupilumab group) and 125 children on placebo during VOYAGE initiated dupilumab (100 or 200 mg, according to bodyweight), once every 2 weeks administered by subcutaneous injection (placebo/dupilumab group). Following a protocol amendment, for a subset of children weighing 30 kg or less, the dose was changed to 300 mg once every 4 weeks. The primary endpoint for the open-label extension study was the number and proportion of patients with any treatment-emergent adverse event (TEAE) during the 52-week study period in the overall population (defined as children aged 6-11 years old with moderate-to-severe asthma who previously completed VOYAGE). Statistical analyses were descriptive. This study is registered with ClinicalTrials.gov (NCT03560466; EXCURSION). FINDINGS: Children who completed VOYAGE were eligible to enrol in EXCURSION between June 21, 2018 and Aug 18, 2020. During EXCURSION, the safety profile and proportion of patients reporting TEAEs were consistent with those observed during the parent study (VOYAGE). In the overall population, 232 (63·6%) of 365 patients experienced at least one TEAE (dupilumab/dupilumab: 147 [61·3%]; placebo/dupilumab: 85 [68·0%]). The most frequently reported TEAEs were nasopharyngitis, pharyngitis, and upper respiratory tract infections. INTERPRETATION: In EXCURSION, long-term treatment with dupilumab was well tolerated with an acceptable safety profile. FUNDING: Sanofi and Regeneron Pharmaceuticals.

Peanut allergen exposure through saliva: assessment and interventions to reduce exposure.

BACKGROUND: Exposure to food allergens through saliva (kissing, utensils) can cause local and systemic allergic reactions. OBJECTIVE: To determine the time course of peanut allergen (Ara h 1) persistence in saliva after ingestion of peanut butter and to evaluate mouth cleansing interventions to reduce salivary peanut allergen. METHODS: Thirty-eight individuals ingested 2 tablespoons of peanut butter, and saliva was collected at various time points. At another time, samples were collected after 5 interventions (brushing teeth, brushing and rinsing, rinsing, waiting then brushing, waiting then chewing gum). Detection of Ara h 1 was performed by a monoclonal-based ELISA (detection limit, 15-20 ng/mL). RESULTS: Salivary Ara h 1 varied considerably immediately after ingestion, but included levels expected to invoke reactions (as much as 40 microg/mL). Most (87%) subjects with detectable peanut after a meal had undetectable levels by 1 hour with no interventions. None had detectable levels several hours later after a peanut-free lunch. This result indicates (95% confidence) that 90% would have undetectable Ara h 1 in saliva under these circumstances. All of the interventions reduced salivary Ara h 1, in some cases by >95%, but Ara h 1 remained detectable in approximately 40% of samples (though typically below thresholds reported to induce reactions). CONCLUSION: Patients with peanut allergy require counseling regarding risks of kissing or sharing utensils, even if partners have brushed teeth or chewed gum. Advice to reduce risks, though not as ideal as total avoidance, includes waiting a few hours plus eating a peanut-free meal. CLINICAL IMPLICATIONS: Waiting several hours and ingesting a peanut-free meal were more effective at reducing salivary peanut protein concentration than simple, immediate interventions.