Allergen Immunotherapy Shows Preventative, Therapeutic Benefits for Allergic Asthma

Laurent Mascarell, PhD

Credit: Laurent Mascarell on LinkedIn

A new literature review is calling attention to the benefits of allergen immunotherapy for allergic asthma, citing its ability to improve symptoms as well as prevent the onset and worsening of the condition.¹

The article, authored by Laurent Mascarell, PhD, head of Innovation and Science at Stallergenes Greer, and colleagues, highlights allergen immunotherapy as a disease-modifying treatment that addresses the underlying causes of IgE-mediated allergies, advocating for its integration into standard asthma management protocols given its significance in both the prevention and treatment of allergic asthma. Unlike conventional pharmacotherapy and biological therapies, which primarily manage symptoms, allergen immunotherapy offers long-term clinical benefits, including the prevention of asthma onset in individuals with allergic rhinitis and the mitigation of worsening asthma in diagnosed patients.¹

Conventional Pharmacotherapy for Asthma, Unmet Needs in Severe Asthma

Asthma management seeks to control symptoms, prevent asthma exacerbations, and minimize future risk of persistent airflow limitation, asthma-related death, and treatment-related side effects. Investigators noted treatment generally depends on asthma severity, with severe asthma defined as asthma requiring a high level of conventional pharmacological treatment, including inhaled corticosteroids.¹

An estimated 3% to 13% of asthmatic patients suffer from a severe form of asthma, accounting for > 50% of the asthma-related economic burden. In addition to inhaled corticosteroids, patients with severe asthma are also treated with short-acting β2 agonists or long-acting β2 agonists, but around 4% to 20% of them do not respond to these guideline-based treatments.¹

Biological Therapies for Asthma

Several monoclonal antibodies have been registered to treat moderate-to-severe asthma, largely targeting inflammation and intended to treat type 2 asthma, especially allergic asthma, which affects an estimated 60% of the 25 million people in the US who have asthma.² Investigators asserted that biologics have revolutionized the management of severe asthma by reducing asthma exacerbations, improving asthma control, reducing the use of corticosteroids, and improving lung function and asthma-related quality of life.¹

While type 2 asthma, including allergic asthma, is generally associated with a good response to type 2-targeted biologics, not all patients respond to conventional pharmacotherapy and biological therapies. Additionally, in most patients with severe asthma, the benefits of biologics are only maintained during treatment, and discontinuation can lead to a resurgence of asthma exacerbations and/or loss of asthma control, underscoring the need for truly curative approaches.¹

Allergen Immunotherapy for Allergic Asthma

Currently, allergen immunotherapy is the only treatment known to address the underlying cause of IgE-mediated allergies, offering long-term clinical benefits after its discontinuation. This disease-modifying treatment consists of the administration of increasing doses of allergen extract followed by the delivery of a maintenance dose, resulting in the dampening of allergen-specific type 2 immunity and in the production of ‘blocking’ IgG and IgA antibodies that prevent IgE from binding to allergens.¹

Additionally, beyond treating the condition in patients with established allergic asthma, investigators noted allergen immunotherapy has the potential to prevent patients with allergic rhinitis from developing allergic asthma. Allergic rhinitis and allergic asthma have been hypothesized to represent a continuum of disease, and rhinitis is a known risk factor for subsequent asthma development – thus, allergen immunotherapy-driven prevention or reduction of allergic asthma may benefit allergic rhinitis.¹

Investigators identified 14 prospective clinical studies of allergen immunotherapy’s preventive potential on asthma development. They involved > 1700 children, adolescents, and adults with allergic rhinitis and found allergen immunotherapy prevents the development of asthma in patients with allergic rhinitis. Of note, this preventive effect appeared to be maintained for years after allergen immunotherapy termination.¹

They additionally identified 9 retrospective studies addressing the preventive effect of allergen immunotherapy on asthma development, including either subcutaneous or sublingual administration of natural extracts or allergoids. These studies included > 840,000 children, adolescents, and adults with allergies to seasonal or perennial allergens. According to all but 1 of these studies, the risk of developing asthma was significantly lower in subjects receiving allergen immunotherapy compared with control patients.¹

Another 7 studies addressing allergen immunotherapy’s prevention of asthma worsening in > 765,000 children, adolescents, and adults suffering from allergies to seasonal or perennial allergens found allergen immunotherapy significantly prevents the progression of asthma, especially from mild to more severe asthma.¹

In all but 1 of 6 prospective clinical studies on allergen immunotherapy treatment of allergic asthma in > 2500 patients, investigators noted the benefit of allergen immunotherapy in the treatment of asthma was confirmed, provided the dose of extract administered was sufficiently high.¹

Real-world retrospective database analyses support the long-term benefit of allergen immunotherapy as a treatment of allergic asthma. Investigators assessed 4 papers involving > 160,000 patients followed for up to 9 years, all of which reported a greater reduction of asthma pharmacotherapy prescriptions during the follow-up period in patients having received allergen immunotherapy compared with control patients.¹

Acknowledging the fact that allergen immunotherapy is contraindicated in patients with severe, uncontrolled, or poorly controlled asthma due to the associated increased risk of systemic allergic reactions, investigators called attention to its use in combination with a biological therapy to bring the benefits of allergen immunotherapy to patients who are a priori not eligible for it.¹

Conclusion

Based on the available evidence, investigators asserted that allergen immunotherapy is the only disease-modifying approach to the treatment of allergy, highlighting its utility for patients with allergic rhinitis, patients who have established allergic asthma, and in combination with biological therapy.¹

“Beyond the prospective clinical trials and long-term retrospective real-world studies that have already been conducted, there is a need for long-term prospective phase 3 RCTs to further support the role of allergen immunotherapy, especially SLIT, in the management of asthma,” investigators concluded.¹

References

1. ^{Batard T, Taillé C, Guilleminault L, et al. Allergen Immunotherapy for the Prevention and Treatment of Asthma. Clinical and Experimental Allergy. https://doi.org/10.1111/cea.14575}
2. ^{Cleveland Clinic. Allergic Asthma. February 7, 2024. Accessed October 15, 2024. https://my.clevelandclinic.org/health/diseases/21461-allergic-asthma}