Juan José Yepes-Nuñez 1, Gordon H Guyatt 2, Luis Guillermo Gómez-Escobar 3, Lucia C Pérez-Herrera 3, Alexandro W L Chu 4, Renata Ceccaci 4, Ana Sofía Acosta-Madiedo 3, Aaron Wen 4, Sergio Moreno-López 3, Margaret MacDonald 4, Mónica Barrios 3, Xiajing Chu 5, Nazmul Islam 6, Ya Gao 5, Melanie M Wong 4, Rachel Couban 7, Elizabeth Garcia 8, Edgardo Chapman 8, Paul Oykhman 4, Lina Chen 9, Tonya Winders 10, Rachel Netahe Asiniwasis 11, Mark Boguniewicz 12, Anna De Benedetto 13, Kathy Ellison 14, Winfred T Frazier 15, Matthew Greenhawt 16, Joey Huynh 17, Elaine Kim 18, Jennifer LeBovidge 19, Mary Laura Lind 20, Peter Lio 21, Stephen A Martin 22, Monica O'Brien 23, Peck Y Ong 24, Jonathan I Silverberg 25, Jonathan Spergel 26, Julie Wang 27, Kathryn E Wheeler 28, Lynda Schneider 19, Derek K Chu 29
Abstract
Background: Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli such as allergens, irritants, and microbes. The role of environmental allergens (aeroallergens) in triggering AD remains unclear.
Objective: We systematically synthesized evidence regarding the benefits and harms of allergen immunotherapy (AIT) for AD.
Methods: As part of the 2022 American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters AD Guideline update, we searched the MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Global Resource for Eczema Trials, and Web of Science databases from inception to December 2021 for randomized controlled trials comparing subcutaneous immunotherapy (SCIT), sublingual immunotherapy (SLIT), and/or no AIT (placebo or standard care) for guideline panel-defined patient-important outcomes: AD severity, itch, AD-related quality of life (QoL), flares, and adverse events. Raters independently screened, extracted data, and assessed risk of bias in duplicate. We synthesized intervention effects using frequentist and Bayesian random-effects models. The GRADE approach determined the quality of evidence.
Results: Twenty-three randomized controlled trials including 1957 adult and pediatric patients sensitized primarily to house dust mite showed that add-on SCIT and SLIT have similar relative and absolute effects and likely result in important improvements in AD severity, defined as a 50% reduction in SCORing Atopic Dermatitis (risk ratio [95% confidence interval] 1.53 [1.31-1.78]; 26% vs 40%, absolute difference 14%) and QoL, defined as an improvement in Dermatology Life Quality Index by 4 points or more (risk ratio [95% confidence interval] 1.44 [1.03-2.01]; 39% vs 56%, absolute difference 17%; both outcomes moderate certainty). Both routes of AIT increased adverse events (risk ratio [95% confidence interval] 1.61 [1.44-1.79]; 66% with SCIT vs 41% with placebo; 13% with SLIT vs 8% with placebo; high certainty). AIT's effect on sleep disturbance and eczema flares was very uncertain. Subgroup and sensitivity analyses were consistent with the main findings.
Conclusions: SCIT and SLIT to aeroallergens, particularly house dust mite, can similarly and importantly improve AD severity and QoL. SCIT increases adverse effects more than SLIT. These findings support a multidisciplinary and shared decision-making approach to optimally managing AD.
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