PMID- 37972922
OWN - NLM
STAT- MEDLINE
DCOM- 20240109
LR  - 20240223
IS  - 2213-2201 (Electronic)
VI  - 12
IP  - 1
DP  - 2024 Jan
TI  - Anaphylaxis in Clinical Trials of Sublingual Immunotherapy Tablets.
PG  - 85-95.e4
LID - S2213-2198(23)01253-9 [pii]
LID - 10.1016/j.jaip.2023.11.011 [doi]
AB  - BACKGROUND: There is no consensus method to identify anaphylaxis in sublingual 
      immunotherapy (SLIT) trials. Standardized Medical Dictionary for Regulatory 
      Activities (MedDRA) queries (SMQs) are standardized groupings of MedDRA terms 
      used in drug safety monitoring. OBJECTIVE: To develop a method to identify 
      potential anaphylaxis in SLIT-tablet trials using SMQ searches and case 
      definitions of anaphylaxis adopted from the National Institute of Allergy and 
      Infectious Disease. METHODS: The SMQ search tool contained 2 criteria including 
      treatment-emergent adverse events (AEs): (1) narrow MedDRA terms related to 
      anaphylaxis and (2) all AEs with broad MedDRA terms from at least 2 of 3 
      categories (respiratory/skin/cardiovascular) occurring on the same day. Criteria 
      were applied to a pooled data set of all subjects from 48 timothy grass, ragweed, 
      house dust mite, and tree SLIT-tablet trials (SLIT-tablet, N = 8200; placebo, N = 
      7033). Additional search strategies were any treatment-emergent AE with MedDRA 
      preferred term "hypersensitivity" and epinephrine administrations. Identified 
      potential cases underwent blinded independent medical expert review. 
      Nonanaphylaxis cases were designated local AEs or mild to moderate systemic 
      reactions. RESULTS: Using the SMQ search tool and after subsequent medical 
      review, 8 anaphylaxis cases were identified; 3 were considered treatment-related, 
      resulting in a proportion of anaphylaxis cases/subject of 0.02% (2 of 8200) with 
      SLIT-tablet and 0.01% (1 of 7033) with placebo. One additional anaphylaxis case 
      related to SLIT-tablet was identified by the preferred term "hypersensitivity." 
      The 3 anaphylaxis cases associated with SLIT-tablet treatment were not 
      life-threatening. The epinephrine administration rate was 17 of 8200 (0.2%) with 
      SLIT-tablet treatment and 2 of 7033 (0.03%) with placebo. CONCLUSIONS: SMQ search 
      criteria for identifying potential anaphylaxis related to SLIT were developed. 
      Anaphylaxis was rare for SLIT-tablets.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Nolte, Hendrik
AU  - Nolte H
AD  - ALK, Bedminster, NJ. Electronic address: Hendrik.nolte@alk.net.
FAU - Calderon, Moises A
AU  - Calderon MA
AD  - University of Costa Rica, San Jose, Costa Rica.
FAU - Bernstein, David I
AU  - Bernstein DI
AD  - Bernstein Allergy Group, Inc, Cincinnati, Ohio; Department of Internal Medicine, 
      The University of Cincinnati College of Medicine, Cincinnati, Ohio.
FAU - Roberts, Graham
AU  - Roberts G
AD  - The David Hide Asthma and Allergy Research Centre, St Mary's Hospital, Newport 
      Isle of Wight, United Kingdom; NIHR Biomedical Research Centre, University 
      Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom; 
      University of Southampton, Southampton, United Kingdom.
FAU - Azuma, Ryuji
AU  - Azuma R
AD  - Torii Pharmaceutical Co, Ltd, Tokyo, Japan.
FAU - Juhl, Ruta Gronskyte
AU  - Juhl RG
AD  - ALK, Horsholm, Denmark.
FAU - Hulstrom, Veronica
AU  - Hulstrom V
AD  - ALK, Horsholm, Denmark.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231114
PL  - United States
TA  - J Allergy Clin Immunol Pract
JT  - The journal of allergy and clinical immunology. In practice
JID - 101597220
RN  - YKH834O4BH (Epinephrine)
RN  - 0 (Tablets)
RN  - 0 (Allergens)
SB  - IM
MH  - Animals
MH  - Humans
MH  - *Anaphylaxis/complications
MH  - *Sublingual Immunotherapy/adverse effects/methods
MH  - Pyroglyphidae
MH  - Epinephrine
MH  - Tablets
MH  - Allergens/therapeutic use
MH  - *Rhinitis, Allergic/therapy
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Allergic rhinitis
OT  - Allergy immunotherapy
OT  - Anaphylaxis
OT  - Epinephrine
OT  - Grass
OT  - House dust mite
OT  - Ragweed
OT  - Sampson criteria
OT  - Standardized MedDRA queries
OT  - Sublingual immunotherapy
OT  - Systemic allergic reaction
OT  - Tree
EDAT- 2023/11/17 15:27
MHDA- 2024/01/09 06:42
CRDT- 2023/11/16 19:30
PHST- 2023/04/06 00:00 [received]
PHST- 2023/11/03 00:00 [revised]
PHST- 2023/11/07 00:00 [accepted]
PHST- 2024/01/09 06:42 [medline]
PHST- 2023/11/17 15:27 [pubmed]
PHST- 2023/11/16 19:30 [entrez]
AID - S2213-2198(23)01253-9 [pii]
AID - 10.1016/j.jaip.2023.11.011 [doi]
PST - ppublish
SO  - J Allergy Clin Immunol Pract. 2024 Jan;12(1):85-95.e4. doi: 
      10.1016/j.jaip.2023.11.011. Epub 2023 Nov 14.