Anaphylaxis in clinical trials of sublingual immunotherapy tablets
Anaphylaxis in clinical trials of sublingual immunotherapy tablets
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.
Allergic rhinitis, Allergy immunotherapy, Anaphylaxis, Epinephrine, Grass, House dust mite, Ragweed, Sampson criteria, Standardized MedDRA queries, Sublingual immunotherapy, Systemic allergic reaction, Tree
85-95.e4
Nolte, Hendrik
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Calderon, Moisés A.
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Bernstein, David I.
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Roberts, Graham
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Azuma, Ryuji
df09aefd-5eb6-4072-a164-5128e4354256
Juhl, Ruta Gronskyte
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Hulstrøm, Veronica
49561dcd-aa4c-4b26-9987-a770624a9fd7
January 2024
Nolte, Hendrik
1f5625c7-8379-4398-bf26-51eb194edc5c
Calderon, Moisés A.
f4e605dc-1a4b-4575-b5e2-d05bd3532b85
Bernstein, David I.
09f7ab15-a526-4e48-9d8f-2653c3baf86b
Roberts, Graham
ea00db4e-84e7-4b39-8273-9b71dbd7e2f3
Azuma, Ryuji
df09aefd-5eb6-4072-a164-5128e4354256
Juhl, Ruta Gronskyte
26f0f79b-d2d3-473f-adc3-fb67a71cbb46
Hulstrøm, Veronica
49561dcd-aa4c-4b26-9987-a770624a9fd7
Nolte, Hendrik, Calderon, Moisés A., Bernstein, David I., Roberts, Graham, Azuma, Ryuji, Juhl, Ruta Gronskyte and Hulstrøm, Veronica
(2024)
Anaphylaxis in clinical trials of sublingual immunotherapy tablets.
Journal of Allergy and Clinical Immunology: In Practice, 12 (1), .
(doi:10.1016/j.jaip.2023.11.011).
Abstract
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.
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Accepted/In Press date: 7 November 2023
e-pub ahead of print date: 14 November 2023
Published date: January 2024
Additional Information:
Publisher Copyright:
© 2023 The Authors
Keywords:
Allergic rhinitis, Allergy immunotherapy, Anaphylaxis, Epinephrine, Grass, House dust mite, Ragweed, Sampson criteria, Standardized MedDRA queries, Sublingual immunotherapy, Systemic allergic reaction, Tree
Identifiers
Local EPrints ID: 484954
URI: http://eprints.soton.ac.uk/id/eprint/484954
ISSN: 2213-2198
PURE UUID: 993f0e7c-8d54-4e4a-88ac-67732e709e8c
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Date deposited: 27 Nov 2023 17:31
Last modified: 12 Apr 2024 01:39
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Contributors
Author:
Hendrik Nolte
Author:
Moisés A. Calderon
Author:
David I. Bernstein
Author:
Ryuji Azuma
Author:
Ruta Gronskyte Juhl
Author:
Veronica Hulstrøm
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