The “big three” inhalation allergens in Central Europe are grass pollen, tree pollen and the house dust mite. Allergen-specific immunotherapy (AIT) is the most effective tool to stop them. Asthma that already exists or develops as a result of the allergy is the second fly that can be swatted with this flap.
Changes in climatic conditions have meant that allergies are no longer a purely seasonal issue. “If a patient reacts to tree pollen, it can start as early as December. If he also reacts to grasses, it continues into the fall, and if herbs are added to the mix, you can actually speak of a year-round allergy,” explained Prof. Dr. Boris Haxel, Clinic for Ear, Nose and Throat Medicine, Head and Neck Surgery (ENT), Schwarzwald-Baar Klinikum in Villingen-Schwenningen (Germany) [1]. In such cases, it is important to identify the triggering allergen and find out how the affected person can be helped most effectively. Often a patient is not only allergic to one allergen, but suffers from polysensitization – between 60 and 80% of adults are affected by this. The result is an increase in polyallergic patients.
Diagnostics and therapy
The medical history is the basis of the diagnosis: when does the patient have symptoms, how do they manifest themselves, what potential differential diagnoses are there? Skin testing is a good option for quickly testing a relatively large number of allergens with regard to sensitization, “but you also have to bear in mind that these prick test solutions are mixtures, which means that we cannot selectively detect all allergens,” Prof. Haxel pointed out. Serology is therefore often important in order to differentiate between polysensitized patients. In individual cases – especially with year-round allergens – a provocation may be useful to confirm the diagnosis and establish that an allergy is actually present and not just a sensitization before initiating allergen-specific immunotherapy. Component-based specific IgE determination provides good options for separating major and minor allergens, which also has an impact on the choice of therapy, according to the allergist.
Therapeutically, abstinence is still the top priority – the better contact with allergens is avoided or eliminated, the better for the patient. This is relatively easy with food, but often difficult with pets for emotional reasons. It is also rather complicated to completely eliminate house dust mites.
Symptomatic therapy is a key pillar. “That’s what patients often do without us doctors: Go to the pharmacy and get a topical nasal steroid or an antihistamine.” However, this only alleviates the symptoms and has no effect on the allergy itself. Biologics can be useful for certain patients, but not for all. In addition, they are generally not as effective as allergen-specific immunotherapy, nor do they have the same disease-modifying effect.
Application route not a criterion for efficacy
In allergen-specific immunotherapy, the allergen dose is slowly increased and thus increasing allergy tolerance is achieved over a period of three years. This method is particularly useful for pollen, house dust and storage mites, animal epithelia, molds and insect toxins. Subcutaneous application (SCIT) and sublingual application (SLIT) are available. According to the S2k guideline, semi-depot preparations with adjuvants or allergoids are currently used for SCIT, while aqueous extracts and tablets are used for SLIT [2] (Fig. 1).
The S2k guideline on allergen immunotherapy for IgE-mediated allergic diseases published in 2022 with the involvement of the Swiss Society of Allergology and Immunology (SGAI) stated, among other things, that the route of application is no longer a criterion for efficacy (subcutaneous or sublingual). Instead, a product-specific proof of efficacy is required. The Therapeutic Allergen Regulation (TAV) process is underway with the aim of only having approved medicines on the market for the main allergens by 2026.
The first choice should be preparations with proven evidence and a marketing authorization. “After that, there should be good reason to use a drug as a second choice that does not have this combination of evidence and approval,” says Prof. Haxel. “Products without approval and evidence should be the last option or no option at all.”
The aim of these criteria is to develop products that are demonstrably effective for patients, preferably in the first season. The expert explained that the data for sublingual therapy for grass pollen in particular is now very positive. In a controlled study, a tablet showed a 33% improvement in symptom and medication scores in the first year compared to a placebo [3]. These values were maintained over the three-year therapy and even amounted to 27% in the second follow-up season.
House dust mite allergy sufferers have an increased risk of developing bronchial asthma. “Here, too, there are good study data on HSM-SLIT in asthma patients under ICS reduction: a significant reduction in the risk of a moderate or severe asthma exacerbation vs. placebo was achieved in patients who are already asthmatic.” In the study design [4], HSM allergy sufferers with existing asthma were given two concentrations of the AIT preparation versus placebo with slow reduction of the ICS. “This certainly provokes an exacerbation in some patients, but this was accepted in order to see what else HSM therapy can do for existing asthma.” The study showed that the patients suffered significantly fewer exacerbations than the placebo group, regardless of the dose (Fig. 2). In the cohort with 6 SQ-HDM, the reduction in exacerbations was -31% (p=0.03), in the cohort with 12 SQ-HDM it was -34% (p=0.02).
AIT still having an effect on asthma after 9 years
In patients suffering from allergies to house dust mites, grasses and/or trees, a significant reduction in rhinitis and asthma medication was achieved in a real-world setting when they received allergen-specific immunotherapy [5]. 46,042 patients from a health insurance population with AIT in allergic rhinitis with and without asthma were matched with 92,048 controls. Up to 9 years after the start of treatment – i.e. six years after the end of therapy – those patients who had received AIT against the allergens mentioned required significantly fewer antisymptomatic drugs than the control group. In asthmatics, the risk of hospitalization has also been significantly reduced in the long term. AIT is a decisive factor in the treatment of both allergy sufferers and asthmatics, and should therefore be used more widely than before, concluded Prof. Haxel.
Take-Home-Messages
- AIT is the only disease-modifying therapy for allergic rhinitis and allergic asthma.
- A product-specific view of AIT products is absolutely essential.
- For new hires, preference should be given to preparations with existing approval and scientific proof of efficacy.
Sources:
- Haxel B: News on the therapy of inhalation allergies. Streamed Up HNOLive: Allergology in transition 2024, 24.01.2024.
- Pfaar O, Ankermann T, Augustin M, et al: Guideline on allergen immunotherapy for IgE-mediated allergic diseases. Allergology 2022; 9: 643-702; AWMF registration number: 061-004.
- Durham SR, et al: SQ-standardized sublingual grass immunotherapy: Confirmation of disease modification 2 years after 3 years of treatment in a randomized trial. J Allergy Clin Immunol 2012; 129: 717-725; doi: 10.1016/j.jaci.2011.12.973.
- Virchow JC, Backer V, Kuna P, et al: Efficacy of a House Dust Mite Sublingual Allergen Immunotherapy Tablet in Adults With Allergic Asthma. A Randomized Clinical Trial. JAMA 2016; 315(16): 1715-1725;
doi: 10.1001/jama.2016.3964. - Fritzsching B, Contoli M, Porsbjerg C, et al: Long-term real-world effectiveness of allergy immunotherapy in patients with allergic rhinitis and asthma: Results from the REACT study, a retrospective cohort study. The Lancet Regional Health – Europe 2022; 13: 100275; doi: 10.1016/j.lanepe.2021.100275.
InFo PNEUMOLOGY & ALLERGOLOGY 2024; 6(1): 28-29
