A pediatric randomized, controlled trial of German cockroach subcutaneous immunotherapy - 04/06/24

Doi : 10.1016/j.jaci.2024.04.022

Edward Zoratti, MD ^a,^⁎ , Robert Wood, MD ^b, Anna Pomés, PhD ^d, Ricardo Da Silva Antunes, PhD ^e, Matthew C. Altman, MD, PhD ^f, Basilin Benson, MS ^g, Lisa M. Wheatley, MD, MPH ^c, Kate Cho, MS ^h, Agustin Calatroni, MA, MS ^h, Frederic F. Little, MD ⁱ, J. Pongracic, MD ^j, Melanie Makhija, MD ^j, Gurjit K. Khurana Hershey, MD, PhD ^k, Michael G. Sherenian, MD ^k, Katherine Rivera-Spoljaric, MD ^l, Jeffrey R. Stokes, MD ^l, Michelle A. Gill, MD, PhD ^l, Rebecca S. Gruchalla, MD ^m, Jeffrey Chambliss, MD ^m, Andrew H. Liu, MD ⁿ, Meyer Kattan, MD ^o, Paula J. Busse, MD ^p, Leonard B. Bacharier, MD ^q, William Sheehan, MD ^r, Haejin. Kim, MD ^a, Jill Glesner, BS ^d, Peter J. Gergen, MD, MPH ^c, Alkis Togias, MD ^c, Jessica L. Baucom, BA ^h, Cynthia M. Visness, PhD ^h, Alessandro Sette, PhD ^e, William W. Busse, MD ^s, Daniel J. Jackson, MD ^t
for the
Inner-City Asthma and Childhood Asthma in Urban Settings Consortia
^a Division of Allergy and Immunology, Department of Medicine, Henry Ford Health, Detroit, Mich
^b Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Md
^c National Institute of Allergy and Infectious Diseases, Rockville, Md
^d InBio, Inc, Charlottesville, Va
^e La Jolla Institute for Immunology, La Jolla, Calif
^f Department of Medicine, University of Washington, Seattle, Wash
^g Benaroya Research Institute, Seattle, Wash
^h Rho, Inc, Federal Research Operations, Durham, NC
ⁱ Department of Medicine, Boston University School of Medicine, Boston, Mass
^j Department of Pediatrics, Anne and Robert H. Lurie Children’s Hospital, Chicago, Ill
^k Department of Pediatrics, Cincinnati Children’s Hospital, Cincinnati, Ohio
^l Department of Pediatrics, St Louis Children’s Hospital, St Louis, Mo
^m Department of Pediatrics, University of Texas Southwest Medical Center, Dallas, Tex
ⁿ Department of Pediatrics, Children’s Hospital of Colorado, Aurora, Colo
^o Department of Pediatrics, Columbia University Medical Center, New York, NY
^p Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY
^q Department of Pediatrics, Monroe Carell Children’s Hospital at Vanderbilt University, Nashville, Tenn
^r Department of Pediatrics, Children’s National Hospital, Washington, DC
^s Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis
^t Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wis

^∗Corresponding author: Edward M. Zoratti, MD, 3A34 One Ford Place, Detroit, MI 48202.3A34 One Ford PlaceDetroitMI48202

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Tuesday 04 June 2024

Abstract

Background

Cockroach allergy contributes to morbidity among urban children with asthma. Few trials address the effect of subcutaneous immunotherapy (SCIT) with cockroach allergen among these at-risk children.

Objectives

We sought to determine whether nasal allergen challenge (NAC) responses to cockroach allergen would improve following 1 year of SCIT.

Methods

Urban children with asthma, who were cockroach-sensitized and reactive on NAC, participated in a year-long randomized double-blind placebo-controlled SCIT trial using German cockroach extract. The primary endpoint was the change in mean Total Nasal Symptom Score (TNSS) during NAC after 12 months of SCIT. Changes in nasal transcriptomic responses during NAC, skin prick test wheal size, serum allergen-specific antibody production, and T-cell responses to cockroach allergen were assessed.

Results

Changes in mean NAC TNSS did not differ between SCIT-assigned (n = 28) versus placebo-assigned (n = 29) participants (P = .63). Nasal transcriptomic responses correlated with TNSS, but a treatment effect was not observed. Cockroach serum-specific IgE decreased to a similar extent in both groups, while decreased cockroach skin prick test wheal size was greater among SCIT participants (P = .04). A 200-fold increase in cockroach serum-specific IgG₄ was observed among subjects receiving SCIT (P < .001) but was unchanged in the placebo group. T-cell IL-4 responses following cockroach allergen stimulation decreased to a greater extent among SCIT versus placebo (P = .002), while no effect was observed for IL-10 or IFN-γ.

Conclusions

A year of SCIT failed to alter NAC TNSS and nasal transcriptome responses to cockroach allergen challenge despite systemic effects on allergen-specific skin tests, induction of serum-specific IgG₄ serum production and down-modulation of allergen-stimulated T-cell responses.

Le texte complet de cet article est disponible en PDF.

Key words : Allergen immunotherapy, cockroach allergy, nasal allergen challenge, asthma, urban, transcriptome, antibody, T-cell response, skin prick test

Abbreviations used : AIM, AIT, ANCOVA, CMA, FDR, ICS, NAC, SCIT, SPT, TNSS, TSNEEZ

Plan

CRITICAL (Cockroach Immunotherapy in Children and Adolescents) trial (NCT03541187; NCT03541187?intr=NCT03541187&rank=1). All RNA-sequencing–related study design information and data used in the analyses can be accessed through ImmPort (home) at accession number SDY2492. The raw RNA-sequencing FASTQ data and MINSEQE (Minimum Information about a high-throughput nucleotide SEQuencing Experiment) have been deposited to the National Center for Biotechnology Information Gene Expression Omnibus (geo/) with accession number GSE250580.