Comparison of allergen immunotherapy practice patterns in the United States and Europe

doi:10.1016/S1081-1206(10)60259-1

Annals of Allergy, Asthma & Immunology

Volume 103, Issue 6, December 2009, Pages 451-460

https://doi.org/10.1016/S1081-1206(10)60259-1 Get rights and content

Objective

To discuss important differences and similarities in the allergen specific immunotherapy (SIT) treatment practices for aeroallergen sensitivity in the United States and Europe.

Data Sources

Information on regulation and standardization in the United States and Europe was obtained from a Food and Drug Administration Allergenic Products Advisory Committee meeting, published literature, personal communications, and information obtained from the extract manufacturers.

Study Selection

Information from the published literature included articles known to the authors and acknowledged consultants, textbooks, and PubMed, with search terms dependent on the particular subtopic.

Results

Key differences between Europe and the United States include allergen extract regulation, standardization, formulation, types of allergen extracts, routes of administration, and reimbursement. Most SIT is formulated in US allergists’ offices, whereas virtually all SIT is formulated by extract manufacturers in Europe. Sublingual immunotherapy represents a significant percentage of SIT treatment in Europe (approximately 45%), but only a small percentage of US allergists (approximately 5.9%) prescribe sublingual immunotherapy. Similarities between European and US allergist specialists lie in their perception of SIT and approach to providing optimal SIT care, which is detailed in their practice guidelines.

Conclusion

Significant differences and similarities exist in SIT practice patterns of US and European allergy specialists. The differences lie primarily in the availability of allergen extracts and how these extracts are formulated. A key similarity is that both recognize the need for ongoing research focused on developing safer and more effective SIT.

Section snippets

INTRODUCTION

The practice of allergen specific immunotherapy (SIT) has been used in the treatment of allergic rhinitis and asthma in Europe and the United States for many years, since the first description by Noon in 1911, almost a century ago.¹ In the 1900s, research focused on desensitizing patients with seasonal allergic rhinitis with pollen extract injections was conducted on both sides of the Atlantic, beginning with Noon and Freeman in London, England, and Lowdermilk in Galena, Kansas. Despite similar

Standardization and Regulation in the United States

In the United States, allergen extracts are regulated by the Food and Drug Administration’s (FDA’s) Center for Biologics Evaluation and Research (CBER). The specific regulations regarding allergen extract are primarily found in part 680 of Title 21 of the Code of Federal Regulations.⁴ US allergen extracts are manufactured in 2 forms: standardized and nonstandardized. Nonstandardized extracts have no US standard of potency and report content as either weight/volume, which is the weight of the

SIMILARITIES

Similarities between European and US allergists likely lie in the perception of SIT as a disease-modifying agent and the established practice guidelines that provide recommendations. Although there may be an ongoing debate between Europe and US allergists regarding the number of allergens to include in an allergen extract formulation, there is virtually no disagreement that this treatment can provide long-lasting clinical improvement after discontinuation and potentially prevent the progression

CONCLUSIONS

Significant differences and similarities exist in the allergen immunotherapy practice patterns of US and European allergy specialists. The differences lie primarily in the availability of allergen extracts and how these extracts are formulated, and both of these factors are influenced by regulatory guidelines. In Europe, extract manufacturers prepare the final finished allergen formulation, often provided as named-patient products, whereas this role is played by allergy specialists in the

ACKNOWLEDGMENTS

We acknowledge the following: Greg Plunkett, PhD, Robert Esch, PhD, Derek Constable, PhD, and Donald W. Aaronson, MD, JD, MPH.

CME Examination

1-5, Cox LS. 2009;103:451-460.

CME Test Questions

1.
An allergen extract standardization procedure that establishes extract potency by comparison with pooled sera from an allergic population, such as the ID₅₀EAL method:
- a.
  can determine if a relevant allergen is missing
- b.
  provides information about the overall allergenicity of the extract
- c.
  will ensure that the allergen extracts with the same labeled potency have similar compositions
- d.
  correlates with the weight of the source material extracted with a given volume of extracting fluid (wt/vol)
- e.
  will determine

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Cited by (154)

The Art of Dosing for Subcutaneous Immunotherapy in North America
2024, Journal of Allergy and Clinical Immunology: In Practice
Subcutaneous immunotherapy (SCIT) is a long-established treatment option for allergic rhinoconjunctivitis. Proper dosing of the allergens is critical for the efficacy and safety of SCIT. Of the hundreds of liquid allergen extracts in the United States, effective and well-tolerated SCIT dosing has only been established for a small number. Thus, SCIT dosing remains largely empiric and continues to be, by necessity, an art. To highlight the complexity of SCIT dosing, this review summarizes the historical and current landscape of U.S. allergen extracts, differences among U.S. and European allergen extracts, allergen selection for SCIT, considerations for compounding of allergen extract mixtures, and recommended dosing. As of 2021, 18 standardized allergen extracts are available in the United States; all other extracts remain unstandardized without characterization of allergen content or potency. U.S. allergen extracts differ from European extracts in formulation and potency characterization. There is no standardized methodology for SCIT allergen selection, and interpretation of allergen sensitization is not straightforward. Compounding of SCIT mixtures requires consideration of potential dilution effects, allergen cross-reactivity, proteolytic activity, and additives. Probable effective dose ranges for SCIT are recommended in U.S. allergy immunotherapy practice parameters, although there are few studies using U.S. extracts supporting these doses as therapeutic. In contrast, optimized doses of sublingual immunotherapy tablets have been confirmed in North American phase 3 trials. The SCIT dosing for each patient remains an art that requires clinical experience and consideration of polysensitization, tolerability, compounding of allergen extract mixtures, and the range of recommended doses within the context of extract potency variability.
Real-world, long-term effectiveness of allergy immunotherapy in allergic rhinitis: Subgroup analyses of the REACT study
2023, Journal of Allergy and Clinical Immunology
Randomized controlled trials have demonstrated the efficacy of allergy immunotherapy (AIT) in allergic rhinitis (AR) and the disease-modifying effects of the SQ grass sublingual immunotherapy (SLIT) tablet.
We sought to assess real-world, long-term effectiveness and safety across AIT subgroups: route of administration, therapeutic allergen, persistence to AIT, and SQ grass SLIT tablet.
The primary outcome of AR prescriptions from a retrospective cohort study (REAl-world effeCtiveness in allergy immunoTherapy; 2007-2017) was assessed across prespecified AIT subgroups in subjects with AR with and without AIT prescriptions (controls). Safety was assessed as anaphylaxis for 2 days or less of the first AIT prescription. Subgroup follow-up continued until samples were fewer than 200 subjects.
Subcutaneous immunotherapy (SCIT) and SLIT tablets showed similarly greater reductions in AR prescriptions than controls (SCIT vs SLIT tablets: year 3, P = .15; year 5, P = .43). Comparably greater reductions in AR prescriptions were observed for grass- and house dust mite–specific AIT than for controls, but significantly smaller reductions were observed for tree-specific AIT (tree vs house dust mite, and vs grass: years 3 and 5, P < .0001). Persistence to AIT was associated with greater reductions in AR prescriptions versus nonpersistence (persistence vs nonpersistence: year 3, P = .09; year 5, P = .006). SQ grass SLIT tablet showed sustained reductions versus controls for up to 7 years (year 3, P = .002; year 5, P = .03). Rates of anaphylactic shock were low (0.000%-0.092%), with no events for SQ SLIT tablets.
These results demonstrate real-world, long-term effectiveness of AIT, complement disease-modifying effects observed in SQ grass SLIT-tablet randomized controlled trials, and highlight the importance of using newer evidence-based AIT products for tree pollen AR.
Comparison of allergen immunotherapy practice patterns in inhalant allergies in the United States of America and Europe: Similarities and differences 2023
2023, World Allergy Organization Journal
IgE-mediated atopic diseases such as allergic rhinitis and rhinoconjunctivitis are common chronic diseases in the western world. Allergen immunotherapy (AIT) plays a fundamental role in the treatment of allergic patients by modulating the underlying immune mechanisms. Though this treatment is integrated in practice-patterns globally, many differences are found in the application of AIT on the national or international level due to heterogeneous methods, and clinical recommendations are given in different parts of the world.
This review from authors in Europe and the United States highlights differences and similarities in important aspects of AIT application in the 2 global regions. First, the regulatory situation differs regarding marketing authorization and licensing. Secondly, differences are elaborated in manufacturing practices, marketing distribution and formulations of AIT products. Thirdly, clinical administration patterns in the current guidelines show similarities in indications and contraindications of AIT, but also are divergent in some practical aspects.
Informing the readership on similarities, as well as differences of standards in AIT in the United States and Europe, the authors highlight the unmet need of thorough harmonization of standards of AIT, as it is the only disease modifying treatment option available for patients with allergic rhinitis and rhinoconjunctivitis.
Treating allergies via skin – Recent advances in cutaneous allergen immunotherapy
2022, Advanced Drug Delivery Reviews
Subcutaneous allergen immunotherapy has been practiced clinically for decades to treat airborne allergies. Recently, the cutaneous route, which exploits the immunocompetence of the skin has received attention, which is evident from attempts to use it to treat peanut allergy. Delivery of allergens into the skin is inherently impeded by the barrier imposed by stratum corneum, the top layer of the skin. While the stratum corneum barrier must be overcome for efficient allergen delivery, excessive disruption of this layer can predispose to development of allergic inflammation. Thus, the most desirable allergen delivery approach must provide a balance between the level of skin disruption and the amount of allergen delivered. Such an approach should aim to achieve high allergen delivery efficiency across various skin types independent of age and ethnicity, and optimize variables such as safety profile, allergen dosage, treatment frequency, application time and patient compliance. The ability to precisely quantify the amount of allergen being delivered into the skin is crucial since it can allow for allergen dose optimization and can promote consistency and reproducibility in treatment response. In this work we review prominent cutaneous delivery approaches, and offer a perspective on further improvisation in cutaneous allergen-specific immunotherapy.
Guidelines for the prescription of allergen immunotherapy and patient follow-up — Clinical questions and revision of the literature
2021, Revue Francaise d'Allergologie
L’immunothérapie allergénique (ITA) aux allergènes respiratoires est à ce jour le seul traitement curatif des allergies. Nous avons précédemment publié la liste des recommandations pour la pratique cliniques (RPC) nationales pour la prescription de l’ITA et le suivi du patient. Pour la réalisation de ce travail, un groupe de plus de 50 allergologues français a rédigé un texte exhaustif basé sur 50 questions cliniques pratiques pour les prescripteurs d’ITA. Ces questions ont été classées en 7 groupes, pour focaliser l’attention sur le choix du patient, les indications et modalité de prescription d’une ITA, les schémas thérapeutiques, les voies d’administration de l’ITA, son efficacité et sécurité, le choix de l’allergène, le suivi du patient et sur d’autres aspects pratiques sur lesquels les allergologues peuvent s’interroger lors de la prescription d’un tel traitement. Les réponses aux 50 questions sont basées sur les résultats des études publiées dans la littérature, et, en cas d’impossibilité à repérer des données solides, sur l’avis des experts. Le but principal de ce travail est de donner aux prescripteurs un tableau clair des données les plus récentes et de les guider dans le choix du traitement optimal pour leur patients allergiques, en tenant compte de l’utilité pratique des questions, qui incluent aussi un regard sur le contexte clinique actuel de pandémie à SARS-CoV-2.
Allergen immunotherapy (AIT) for respiratory allergens is the only curative treatment for allergies. We previously published the list of the French National Clinical Practice Guidelines for AIT prescription and patient's monitoring. To carry out this work, a group of more than 50 French allergists wrote an exhaustive text answering 50 clinical questions that meet the specific needs of AIT prescribers. These questions have been classified into 7 groups, to focus on patient's choice, the indications and modalities of AIT prescription, treatment regimens, the routes of administration of AIT, its efficacy and safety, the choice of the allergen, patients’ follow-up and on other practical aspects that allergists may wonder about when prescribing such treatment. Answers to the 50 questions are based on the results of studies published in the literature, and, if hard data could not be found, on experts’ advice. The main goal of this work is to provide prescribers a clear picture of the most recent data and to guide them in choosing the optimal treatment for their allergic patients, taking into account the practical questions, which also include a look to the current clinical context, due to the SARS-CoV-2 pandemic.
A WAO — ARIA — GA<sup>2</sup>LEN consensus document on molecular-based allergy diagnosis (PAMD@): Update 2020
2020, World Allergy Organization Journal
Precision allergy molecular diagnostic applications (PAMD@) is increasingly entering routine care. Currently, more than 130 allergenic molecules from more than 50 allergy sources are commercially available for in vitro specific immunoglobulin E (sIgE) testing. Since the last publication of this consensus document, a great deal of new information has become available regarding this topic, with over 100 publications in the last year alone. It thus seems quite reasonable to publish an update. It is imperative that clinicians and immunologists specifically trained in allergology keep abreast of the new and rapidly evolving evidence available for PAMD@.
PAMD@ may initially appear complex to interpret; however, with increasing experience, the information gained provides relevant information for the allergist. This is especially true for food allergy, Hymenoptera allergy, and for the selection of allergen immunotherapy. Nevertheless, all sIgE tests, including PAMD@, should be evaluated within the framework of a patient's clinical history, because allergen sensitization does not necessarily imply clinical relevant allergies.

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This educational activity is supported by an educational grant from GlaxoSmithKline

Previous Presentation: This paper was presented at the European Academy of Allergy Asthma and Immunology Annual Meeting on June 7, 2009 in Warsaw, Poland at Immunotherapy Interest Section Business Meeting invited by Giovanni Passalacqua, MD (chair) and Moises Calderon, MD, PhD (secretary).

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CME Review ArticleComparison of allergen immunotherapy practice patterns in the United States and Europe

Objective

Data Sources

Study Selection

Results

Conclusion

Section snippets

INTRODUCTION

Standardization and Regulation in the United States

SIMILARITIES

CONCLUSIONS

ACKNOWLEDGMENTS

CME Examination

CME Test Questions

Lancet

J Allergy Clin Immunol

J Allergy

J Allergy Clin Immunol

J Allergy Clin Immunol

Ann Allergy Asthma Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Ann Allergy Asthma Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Ann Allergy Asthma Immunol

Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10-year follow-up on the PAT study

Allergy

Preparation of standardization of allergen extracts

Allergens of mammalian origin, V: properties of extracts derived from the domestic cat

Clin Allergy

Allergenic extracts, II: in vivo standardization

Assignment of bioequivalent allergy units based on biological standardization methods

Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe Frankf A M

Sample size considerations for establishing clinical bioequivalence of allergen formulations

Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe Frankf A M

CME Review Article
Comparison of allergen immunotherapy practice patterns in the United States and Europe