Sublingual Immunotherapy for Asthma Appears Safe, but More Data on Efficacy Is Needed

Brandon May

November 05, 2021

For individuals with allergic reactions to inhalants, sublingual immunotherapy (SLIT) has been used successfully to induce desensitization and improve immune tolerance, consequently reducing allergic symptoms. Given these effects, researchers suspect SLIT could be useful for the treatment of asthma.

While the current level of evidence supporting the efficacy of SLIT in asthma management is insufficient, research findings published in Clinical & Experimental Allergy suggest the treatment option is safe for the management of other conditions in patients with mild-to-moderate and well-controlled asthma who are at low risk of harm.

Study Findings

In the study, researchers from the National Health Service Healthcare Trust in London, UK, conducted a systematic review of randomized controlled trials comparing SLIT with placebo or standard of care in patients with asthma, rhinitis, or both.

The investigators compared treatment groups with respect to asthma exacerbations requiring emergency department (ED) visits or hospital admission, quality of life, and all-cause serious adverse events (SAEs).

Across the 66 studies included in the review, few reported on the primary efficacy outcomes of asthma exacerbations and quality of life. Of the two studies that did report on exacerbations requiring an ED or hospital visit, the pooled estimate suggested SLIT may reduce exacerbations compared with usual care or placebo (odds ratio [OR] 0.35; 95% CI, 0.10 - 1.20). However, the wide confidence interval rendered the evidence for the benefit of SLIT "very uncertain," according to the investigators.

Safety data were more robust than the efficacy data. The researchers found that SLIT likely did not increase the risk of SAEs relative to usual care or placebo. A risk difference analysis suggested that no more than 1 in 100 patients taking SLIT will experience an SAE, according to moderate-certainty evidence.

SLIT also demonstrated a "general trend" of benefit over placebo regarding changes in inhaled corticosteroid use, exacerbations that required oral steroids, and bronchial provocation. These benefits were also based on low-certainty evidence.

The researchers wrote that the findings "were imprecise and included the possibility of important benefit or little effect and, in some cases, potential harm" associated with SLIT.

In combined results of 27 studies, more patients who took SLIT experienced adverse events than those assigned control (OR, 1.99; 95% CI, 1.49 - 2.67), but these events were generally mild and temporary.

SLIT Drawbacks

To date, the only FDA-approved SLIT treatments are sublingual tablets for ragweed, dust mites, and grass, explained Payel Gupta, MD, an assistant clinical professor at SUNY Downstate Medical Center and Mt. Sinai Medical Center in New York City. She also serves as a national volunteer medical spokesperson for the American Lung Association.

Dr Payel Gupta

Gupta, who wasn't involved in the research, told Medscape Medical News that the concern for using SLIT in patients with asthma relates to potential harms of the therapy, particularly for individuals with moderate-to-severe asthma that is not well controlled. "For these patients, they may have more negative outcomes if they were to have a reaction to the sublingual immunotherapy," she said. "Since their airways already have a lot of inflammation, they might be at more risk of having a life-threatening reaction if they react."

In an email to Medscape, Mark Aronica, MD, a staff member in Cleveland Clinic's pulmonary, allergy, and critical care medicine department, added that there is currently better data to support subcutaneous immunotherapy or allergy shots, two therapies that have been around for more than 100 years.

"However, the major benefit and indication for using sublingual or subcutaneous immunotherapy is in the management of allergic rhinitis," said Aronica, who was not involved in the meta-analysis. "Of course, many people with allergic rhinitis will also have asthma, but asthma by itself would not be an indication for these therapies."

Aronica added that insurance generally doesn't cover SLIT because of its relatively high cost, therefore limiting its wide-scale use in clinical practice. In contrast, subcutaneous immunotherapy is seen as more cost effective, but it may also be more time-consuming and requires routine injections. "Also, most patients with asthma are polysensitized, meaning they are allergic to multiple allergens," he added. "If you have a patient with multiple allergies then they would potentially have to take multiple sublingual tablets."

Gupta, Aronica, and the study researchers have disclosed no relevant financial relationships.

Clin Exp Allergy. Published online September 2, 2021. Full Text

Brandon May is a freelance medical journalist who has written more than 1800 articles for medical publications in the United States and the UK. He resides in New York City. Twitter: @brandonmilesmay

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