Can Early Allergen Immunotherapy Prevent Future Asthma?

Lorraine L. Janeczko, MPH

April 12, 2022

Providing allergen immunotherapy (AIT) to allergy patients, especially children, before they develop asthma may protect them from developing asthma in the future, a systematic review and meta-analysis conducted in Europe suggests.

Mariana Farraia

"This study supports a possible preventive effect of AIT in asthma prevention," lead author Mariana Farraia, MS, a PhD candidate at the Institute of Public Health and the Faculty of Medicine of the University of Porto, in Porto, Portugal, told Medscape Medical News. "These findings may also help improve clinical guidelines on the management of allergic diseases."

The preventive effect seems strongest in children who are monosensitized in therapy lasting at least 3 years, independently of allergen type, Farraia and her co-authors write in Allergy.

Farraia and her colleagues assessed clinical data from all study types to evaluate the role that AIT, administered through any route, played in preventing the onset of asthma. They searched the PubMed, Scopus, and Cochrane databases for articles published in English, Spanish, or Portuguese through early April 2021.

The researchers evaluated studies for quality using risk-of-bias (ROB) tools, and they meta-analyzed data using a random effects model methodology. They performed sensitivity, influence, and subgroup analyses, and they assessed publication bias and heterogeneity.

From 4549 studies the authors identified, they included 24 randomized controlled trials and nonrandomized studies of interventions in the qualitative synthesis. From those 24, they included 18 in the meta-analysis.

One study had low ROB, seven had moderate ROB, and 15 had high ROB. Random-effects analysis showed a 25% decrease in risk of developing asthma following AIT (risk ratio [RR], 0.75; 95% CI, 0.64 – 0.88; N = 17). In the sensitivity analysis, the effect was not significant. Heterogeneity between studies was moderate (I2 = 58%).

Timely AIT Appears to Forestall Asthma Development

In the main findings, subgroup analysis showed a strong preventive effect of AIT for children (RR, 0.71; 95% CI, 0.53 – 0.96) who completed 3 years of therapy (RR, 0.64; 95% CI, 0.47 – 0.88) and in monosensitized patients (RR, 0.49; 95% CI, 0.39 – 0.61).

Sublingual immunotherapy (SLIT) tablets were found to have protective effects, but results were most noticeable for subcutaneous immunotherapy and SLIT drops.

"The increasing prevalence of allergic diseases is a global public health problem," Ferraia noted, "and AIT, a disease-modifying treatment for IgE-mediated diseases, is the only available treatment impacting the progression of allergic diseases.

"Previous studies highlighted AIT's ability to prevent new sensitizations but did not find evidence that AIT played a role in asthma prevention," she said in an email. "These results provide a new opportunity for clinicians and patients to improve the management of allergic diseases."

Farraia added that the review's major limitation is with regard to the quality of the studies and that its major strength is the inclusion of all related studies regardless of design.

"Combining evidence from randomized controlled trials and real-world evidence studies is crucial today to take into account what happens beyond clinical trials," she said.

For Ferraia and her group, "The main question is, How long does this effect last? Because few studies evaluated this preventive role for the long term, the evidence is stronger for short-term effects."

AIT Has Potential as a Vaccine Against Asthma, but More Research Is Needed

Girish V. Vitalpur, MD, FAAP, FAAAAI, associate professor of clinical pediatrics at the Indiana University School of Medicine and director of allergy clinical services at Riley Hospital for Children in Indianapolis, Indiana, pointed out, "The findings suggest that children who are sensitized to one item are most likely to benefit. However, most of our patients are sensitized to several inhalant allergens when we place them on allergy shots." Vitalpur was not involved in the study.

Dr Girish Vitalpur

"So the question of how much AIT can prevent asthma in most children with environmental allergies remains," he added in an email. "Most allergists recommend AIT for three years, and this study confirms that at least three years of AIT is needed to see this benefit."

Dr David Peden

Allergists have long been asking whether giving timely AIT to at-risk patients can prevent future asthma, said David B. Peden, MD, professor of pediatrics, medicine, microbiology, immunology, and toxicology and senior associate dean for translational research at the University of North Carolina School of Medicine at Chapel Hill.

"This important hypothesis-generating structured review builds a good evidence base. It shows the feasibility of the idea that providing AIT — not to every child born, but to people at risk for developing asthma — before they develop the disease might stave off asthma," he told Medscape Medical News.

"The study also shows that the earlier the allergy is recognized and the allergic march is addressed and under control, the more likely you are to control disease and have it be less life-impeding," he added.

Peden, who also was not involved in the study, noted that the feasibility needs to be tested in a prospective clinical trial.

"If subsequent studies support that notion, then preventive care, much like the vaccines we now give to prevent infectious diseases, may follow," he said. "In essence, we would use allergy shots as allergy vaccines to prevent asthma."

The study was funded by the Portuguese National Foundation for Science and Technology (Fundação para a Ciência e Tecnologia). The authors, Vitalpur, and Peden have disclosed no relevant financial relationshps.

Allergy. Published online March 28, 2022. Full text

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