Epinephrine Use in Clinical Trials of Sublingual Immunotherapy Tablets

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• 作者：Hendrik Nolte ; MD ; PhD^a ; ^{hendrik.nolte@merck.com} ; Thomas B. Casale ; MD^b ; Richard F. Lockey ; MD^b ; Bodil Svanholm Fogh ; MSc^c ; Amarjot Kaur ; PhD^a ; Susan Lu ; PharmD^a ; Harold S. Nelson ; MD^d
• 关键词：Adrenaline ; Allergen immunotherapy ; Anaphylaxis ; Epinephrine ; Safety ; Sublingual immunotherapy ; Systemic allergic reaction
• 刊名：The Journal of Allergy and Clinical Immunology: In Practice
• 出版年：2017
• 出版时间：January-February 2017
• 年：2017
• 卷：5
• 期：1
• 页码：84-89.e3
• 全文大小：285 K
• 卷排序：5

文摘

Allergy immunotherapy can result in systemic allergic reactions and even life-threatening anaphylaxis requiring epinephrine administration.ObjectiveThe objective of this study was to describe epinephrine use in the clinical trial development programs of 3 rapidly dissolving sublingual immunotherapy tablets (SLIT-tablets; Merck & Co., Inc., Kenilworth, NJ/ALK, Hørsholm, Denmark/Torii Pharmaceutical Co., Ltd., Tokyo, Japan).MethodsData on epinephrine use were collected from 13 timothy grass SLIT-tablet trials (MK-7243; ≤2800 bioequivalent allergen units/75,000 SQ-T dose, n = 2497; placebo, n = 2139), 5 short ragweed SLIT-tablet trials (MK-3641; ≤12 Amb a 1-U, n = 1725; placebo, n = 770), and 11 house dust mite (HDM) SLIT-tablet trials (MK-8237; ≤12 SQ-HDM; n = 3930; placebo, n = 2246).ResultsIn grass SLIT-tablet trials, epinephrine was used 13 times (grass SLIT-tablet, n = 10; placebo, n = 3). Eight administrations were for grass SLIT-tablet-related adverse events (AEs): 4 for systemic allergic reactions and 4 for local mouth and/or throat swelling. In ragweed SLIT-tablet trials, epinephrine was used 9 times in 8 subjects (ragweed SLIT-tablet, n = 7; placebo, n = 1 [2 administrations for protracted anaphylaxis]). Four administrations were for ragweed SLIT-tablet-related AEs: 1 for systemic allergic reaction and 3 for local mouth and/or pharynx/throat swelling. In HDM SLIT-tablet trials, epinephrine was administered 13 times (HDM SLIT-tablet, n = 8; placebo, n = 5). Four administrations were for HDM SLIT-tablet-related AEs: 1 for systemic allergic reaction and 3 for local events. Of the 16 epinephrine administrations for events related to SLIT-tablet treatment, 11 occurred within the first week of treatment (7 administrations on day 1) and 5 were subject self-administered.ConclusionsEpinephrine administrations in response to SLIT-tablet-related reactions in clinical trials are uncommon, typically occur within the first week of treatment, and are rarely self-administered. All SLIT-tablet-related events treated with epinephrine were nonserious.