Extrapolating Evidence-Based Medicine of AIT Into Clinical Practice in the United States

Calderon MA, Casale TB, Nelson HS et al. J Allergy Clin Immunol Pract. 2023 Apr;11(4):1100-1115. doi: 10.1016/j.jaip.2022.10.033.

Executive Summary

This review sought to critically assess evidence-based medicine (EBM) for debated concepts in US allergy immunotherapy (AIT) practice for respiratory allergies in the context and quality of today’s regulatory standards. In addition, EBM for patient-centered AIT issues and the approach to implementation of AIT EBM in future clinical practice were addressed. The EBM for each concept was briefly summarized, and when possible, a practical, concise recommendation was given.

EBM in debated concepts for AIT: Individuals of all ages can have allergic rhinoconjunctivitis (ARC) and may have multiple allergen sensitivities or comorbid atopic conditions (eg, asthma).

Therefore, there has been much research into the efficacy and safety of AIT for various patient subgroups. Based on the available evidence, single-allergen AIT can effectively treat sensitivity toward that specific allergen, even in polyallergic patients; however, data are still lacking on the efficacy of multiallergen subcutaneous immunotherapy (SCIT) to treat more than 1 clinically relevant sensitivity and effective dosing for multiallergen SCIT. AIT is recommended as a safe and effective therapy across age groups, although in older patients more data are needed to confirm the efficacy of AIT. Comorbidities that could put older patients at a higher risk of an anaphylactic event following AIT administration should be considered. AIT should not be prescribed in patients with severe or uncontrolled asthma, and patients should be screened before injections for loss of asthma control. Initiation of AIT should not occur during pregnancy, but if a woman on AIT becomes pregnant and is receiving a therapeutic dose, she may remain on treatment.

Proper diagnosis of the appropriate allergen sensitivities is a critical component of AIT practice. Skin prick test or allergen-specific serum IgE should be used for the assessment of allergens for AIT. Skin prick test can be affected by technique, age, medications, skin color, and the concentration of the allergen extracts used; therefore, negative and positive controls should always be used. The use of nasal and conjunctival allergen challenges is not recommended for routine diagnosis, but in specialized centers, these challenges may be conducted in patients with both negative skin prick test result and allergen-specific serum IgE who are highly suspected of having ARC. Telemedicine cannot replace in-person care during diagnosis, although it can be complementary to in-person care by providing convenient and high-quality health care access.

There is a dose effect with AIT, and for SCIT, the dose that is well tolerated and falls within the probable effective dose range needs to be determined for each individual. Most of the allergen liquid extracts used for SCIT in the United States were “grandfathered in” without evaluation under today’s standards for regulatory approval. There are currently 18 allergen liquid extracts in the United States that have been standardized for potency. In the United States, use of allergen liquid extracts for sublingual immunotherapy (SLIT)-drop administration is not recommended. Effective SLIT-tablet dosing has been established in clinical trials and should be prescribed in accordance with prescribing labels. To date, there have been no biomarkers identified that correlate with the clinical efficacy of AIT, and the decision to stop or maintain treatment should be based on clinical response. If a patient is responding to treatment, at least 3 years of treatment is recommended to achieve a sustained effect.

EMB for patient-centered AIT issues: As with many treatments, patient adherence to AIT remains a challenge. Shared decision making with patients should be an integral part of AIT practice to optimize adherence and outcomes. The use of digital tools and health care apps is recommended to help remind patients of their SCIT appointments or to take their daily SLIT-tablet dose. Patients should be informed that in addition to improving ARC symptoms, AIT can have the added benefit of reducing ARC-related costs and health care utilization.

Evidence-based guidelines or practice parameters addressing both SCIT and SLIT in the treatment of ARC and asthma are essential documents to inform decision making for patients and health care providers. EBM guidelines and recommendations should be followed by prescribers of AIT and modified for regional factors as necessary.

Future directions for implementing EBM for AIT for tomorrow’s allergy specialists in the United States: Allergy Fellows help shape the future of patient care. To encourage implementation of EBM for AIT, Allergy Fellows need education regarding the available EBM. Training programs for allergy/immunology specialists should increase their focus on AIT, including education on evidence-based dosing and hands-on training for the preparation and mixing of SCIT extracts.

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