Adherence is crucial for treatment success

Allergen-specific immunotherapy can prevent disease progression in the long term by tolerance development in allergic diseases. However, to achieve sustainable effects, long-term therapy is required, which requires a certain degree of adherence on the part of the patient. However, data show that treatment dropout rates are sometimes substantial. Which factors could be decisive for this, or how adherence can be promoted, is a much-discussed practice-relevant topic, on which there are numerous smaller and larger studies.

Allergen-specific immunotherapy (AIT) was formerly also called desensitization or hyposensitization and remains the only causal treatment for IgE-mediated type 1 allergies such as allergic rhinoconjunctivitis, allergic bronchial asthma, and hymenopteran venom allergy. Regular and sufficiently long performance of AIT is central for sustainable therapeutic success. Therefore, adherence or persistence is of great importance (Fig. 1). At this year’s Annual Meeting of the EAACI (European Academy of Allergy and Clinical Immunology), Dr. Enrico Heffler, MD, PhD, Associate Professor of Internal Medicine, Humanitas University, Milano (I), spoke about the current state of knowledge in this field [1].

Efficacy and safety of AIT

Meta-analyses demonstrate well-documented efficacy of AIT in allergic rhinitis/rhinoconjunctivitis, allergic asthma, and insect venom allergy [11]. However, due to the heterogeneity of the individual studies, a blanket recommendation in the sense of a class effect is not possible; rather, the respective benefit-risk profiles should be assessed individually for each AIT preparation. In Switzerland, AIT can be performed by primary care physicians if indicated or after allergological clarification. The exact application of AIT varies depending on the manufacturer and product. Basically, subcutaneous (SCIT) or sublingual (SLIT) forms of application are available. SCIT is administered by a physician, while SLIT can be performed at home (first application is usually under physician supervision with 30-minute monitoring). Thus, more frequent physician visits are required for SCIT. SLIT, on the other hand, usually requires daily applications. With the exception of fixed-dose SLIT tablet preparations, AIT distinguishes an up-dose phase from a maintenance phase. In most cases, a total therapy duration of three years is required for sustainable effects.

Drop-out rates for SCIT and SLIT

A review found no overall differences in adherence rates depending on whether SCIT or SLIT was used [2]. And also from a secondary analysis by Cox et al. indicates that adherence to AIT is not primarily dependent on the mode of administration [12]. Whereby it is also pointed out that methodological differences (e.g., follow-up period, patient population, operationalization of adherence) make it difficult to compare individual studies [4]. Accordingly, data on adherence to AIT are heterogeneous. For example, a retrospective analysis regarding grass pollen AIT in Germany found that 49% and 64% of patients did not renew their SLIT and SCIT prescriptions, respectively, within a two-year period [13]. In contrast, a Dutch retrospective analysis indicates that of a total of 6486 patients treated with AIT, the dropout rate was higher with SLIT than with SCIT: 93% vs 77% discontinued therapy prematurely, i.e., before completion of the recommended three years [14]. And from a real-world study published in 2023, the proportion of patients who completed the first year of AIT was low, particularly for SLIT: only 22.2-27.1% were still on therapy 12 months after initiation, compared with 52.0-64.1% for dSCIT** and 38.3-50.3% for oSCIT^$. This was a large-scale study across different allergen extracts: grass pollen allergy (n=38 717), early-flowering pollen allergy (n=23 183), house dust mite allergy (n=41 728) [3].

** dSCIT = depigmented polymerized allergen extract.
^$ oSCIT= other subcutaneous AIT

Pfaar et al. have suggested the use of a checklist for study purposes in the future, so that constructs and measurement methods are designed in a more uniform and thus more comparable manner [3].

“Shared decision making” as a factor promoting adherence.

The question of what causes a lack of adherence to therapy and how this can be improved is not easy to answer. There appear to be several influencing factors that should be adequately considered in treatment planning. It is essential that patients are thoroughly and carefully informed about the performance of AIT. Across various studies, it has been found that involving patients in decision-making processes and providing them with detailed information about the treatment rationale has a beneficial effect on adherence [5,9]. This is shown, for example, by a Spanish study in which 307 AIT patients were divided into either an active (n=204) or a passive (n=103) group. The active group was given the opportunity to participate in a patient education program and could actively contribute their preferences to treatment decisions. Six months after the start of therapy, the dropout rate in the active group was 11%, while in the control group (received standard information/instruction) this proportion was 21%. Other studies also indicate that patient education and “shared decision making” have a favorable impact on adherence. Patient education refers on the one hand to information on the treatment rationale (e.g. long-term therapy required for sustained effects) as well as advice on possible side effects and possible countermeasures [6,10,16]. The use of digital health tools, for example for educational purposes or therapy monitoring, is also becoming increasingly important.

SCIT: shortened regimen of up-dosing possible?

One study examined the effect on adherence of SCIT patients of administering four rather than seven injections up to the maximum dose [7]. This showed that 90.8% of patients treated with the shortened up-dosing regimen went through at least two years of treatment, and 63.4% continued SCIT for a total of at least three years (Fig. 2) [7]. In comparison, in the control group, only 52.6% completed SCIT ≥2 years of treatment (p=0.0001, Fisher exact test) and 26.8% completed ≥3 years. Furthermore, the drop-out rate in the control group after one year was massively higher at 46.4% compared to 9.1% with shortened regimen (p=0.0001) [7].

SLIT: progress controls and digital health applications

In a publication of the Society for Pediatric Allergology and Environmental Medicine (GPAU), it is recommended to have a personal follow-up appointment in the practice two weeks after starting SLIT and at least every three months thereafter, to ask about any side effects, to offer symptomatic therapy, and to receive information on how to integrate the continuous therapy into everyday life [15]. It has been shown that this can optimize long-term therapy adherence. Digital health applications are another approach to promote adherence [16]. Since SLIT is mostly applied in the home setting by the patients themselves, motivation and routine implementation in the daily routine are critical points. To inquire about treatment efficacy and any side effects, as well as to issue a new prescription if necessary, video consultations have proven to be a useful, resource-saving alternative to in-person physician appointments [17]. Also discussed is the use of reminder systems or a digital feedback system regarding the effectiveness of AIT [18].

Congress: EEACI Annual Meeting

Literature:

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