Allergen immunotherapy: A practice parameter third update

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Contributors

The Joint Task Force has made a concerted effort to acknowledge all contributors to this parameter. If any contributors have been excluded inadvertently, the Task Force will ensure that appropriate recognition of such contributions is made subsequently. The Joint Task Force gratefully acknowledges the AAAAI Board of Directors and the ACAAI Board of Regents for their review and support of this document.

The authors and editors gratefully acknowledge Susan Grupe and Jessica Karle for their

Chief Editors

Linda Cox, MD

Department of Medicine Nova Southeastern University College of Osteopathic Medicine

Davie, Florida

Richard Lockey, MD

Division of Allergy and Immunology

Department of Internal Medicine

University of South Florida College of Medicine and James A. Haley Veterans’ Hospital

Tampa, Florida

Harold Nelson, MD

Department of Medicine

National Jewish Health

Denver, Colorado

Work Group Members

Christopher Calabria, MD

Glen Burnie, Maryland

Thomas Chacko, MD

Roswell, Georgia

Ira Finegold, MD

New York, New York

Michael Nelson, MD, PhD

Washington, DC

Richard Weber, MD

Denver, Colorado

Joint Task Force Reviewers

David Bernstein, MD

Department of Medicine and Environmental Health

University of Cincinnati College of Medicine

Cincinnati, Ohio

David A. Khan, MD

Department of Internal Medicine

University of Texas Southwestern Medical Center

Dallas, Texas

Joann Blessing-Moore, MD

Departments of Medicine and Pediatrics

Stanford University Medical Center

Department of Immunology

Palo Alto, California

David M. Lang, MD

Allergy/Immunology Section

Division of Medicine Allergy and Immunology Fellowship Training Program

Cleveland

Invited Reviewers

Don Aaronson, MD, JD, MPH

Chicago, Illinois

Desiree Larenas-Linnemann, MD

Mexico city, Mexico

Bryan Leatherman, MD

Gulfport, Mississippi

Sandra Y. Lin, MD

Johns Hopkins Department of Otolaryngology–Head & Neck Surgery

Baltimore, Maryland

Oral and sublingual immunotherapy for food hypersensitivity

Wesley Burkes, MD

Duke University

Raleigh, North Carolina

Venom hypersensitivity

David Golden, MD

Baltimore, Maryland

Theodore M. Freeman, MD

Helotes, Texas

Allergen extract section

Derek Constable, PhD

Spokane, Washington

Assigned Reviewers

Paul Greenberger, MD

Northwestern University Feinberg School of Medicine

Chicago, Illinois

Bryan Martin, DO

Ohio State University

Columbus, Ohio

Preface

This document was developed by the Joint Task Force on Practice Parameters, which represents the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma & Immunology (JCAAI).

The objective of “Allergen immunotherapy: a practice parameter third update” is to optimize the practice of allergen immunotherapy for patients with allergic diseases. This parameter is intended to establish guidelines

Key highlights of the update: New developments or modifications

  • New indications for allergen immunotherapy:

    • Atopic dermatitis in subjects with aeroallergen sensitization (Summary Statement 8).

    • VIT: patients who experience recurrent bothersome LLRs (Summary Statement 11).

  • Measurement of baseline tryptase is recommended in patients with moderate or severe anaphylactic reactions to stings. Increased serum tryptase levels are associated with more frequent and severe systemic reactions to VIT injections, greater failure rates during VIT, and greater relapse rates

Algorithm and annotations for immunotherapy

Fig 1 provides an algorithm for the appropriate use of allergen immunotherapy. Given below are annotations for use with the algorithm.

Immunotherapy glossary

For more information on immunotherapy definitions, see the article by Kao.29

The allergen immunotherapy extract is defined as the mixture of the manufacturer’s allergen extract or extracts that is used for allergen immunotherapy. Allergen extracts used to prepare the allergen immunotherapy extract can be complex mixtures containing multiple allergenic and nonallergenic macromolecules (proteins, glycoproteins, and polysaccharides) and low-molecular-weight compounds. Other terms used to describe

Immunologic responses to immunotherapy

Summary Statement 1: The immunologic response to subcutaneous immunotherapy is characterized by decreases in the sensitivity of end organs and changes in the humoral and cellular responses to the administered allergens. A

Summary Statement 2: Reduction in end-organ response with immunotherapy includes decreased early and late responses of the skin, conjunctiva, nasal mucosa, and bronchi to allergen challenge; decreased allergen-induced eosinophil, basophil, and mast cell infiltration; blunting

Allergic rhinitis, allergic asthma, and stinging insect hypersensitivity

Summary Statement 6: Immunotherapy is effective for the treatment of allergic rhinitis, allergic conjunctivitis, allergic asthma, and stinging insect hypersensitivity. Therefore immunotherapy merits consideration in patients with these disorders as a possible treatment option. A

Many double-blind, placebo-controlled randomized clinical trials demonstrate a beneficial effect of immunotherapy under a variety of conditions.74, 75, 76, 77, 78, 79, 80, 81 Immunotherapy is effective for the treatment

Clinical indications for allergic rhinitis and allergic asthma

Summary Statement 7: Allergen immunotherapy should be considered for patients who have demonstrable evidence of specific IgE antibodies to clinically relevant allergens. The decision to begin allergen immunotherapy might depend on a number of factors, including but not limited to patient’s preference/acceptability, adherence, medication requirements, response to avoidance measures, and the adverse effects of medications. D

Randomized, prospective, single- or double-blind, placebo-controlled

Allergen immunotherapy in children

Summary Statement 17: Immunotherapy for children is effective and well tolerated. It has been shown to prevent the new onset of allergen sensitivities in monosensitized patients, as well as progression from allergic rhinitis to asthma. Therefore immunotherapy should be considered along with pharmacotherapy and allergen avoidance in the management of children with allergic rhinitis/rhinoconjunctivitis, allergic asthma, and stinging insect hypersensitivity. B

Immunotherapy for children has been

Time course of improvement

Summary Statement 22: Clinical and physiological improvement can be demonstrated very shortly after the patient reaches a maintenance dose. A

Clinical improvement can be demonstrated very shortly after the patient reaches a maintenance dose.20, 103, 111, 203 One study of patients with cat allergy who achieved the maintenance dose in 5 weeks with a cluster schedule reported the results of titrated nasal allergen challenge, titrated skin prick testing, and allergen-specific IgG4 measurement with

Local reactions

Summary Statement 27: Published studies indicate that individual local reactions do not appear to be predictive of subsequent systemic reactions. However, some patients with a greater frequency of large local reactions might be at an increased risk for future systemic reactions. C

In a survey of 249 patients undergoing immunotherapy, 71% reported experiencing a local reaction.212 Of the patients experiencing local reactions, 84.7% reported reactions smaller than the palm of the hand, and 81.9%

Starting doses

Summary Statement 47: The starting dose for build-up is usually a 1,000-fold or 10,000-fold dilution of the maintenance concentrate, although a lower starting dose might be advisable for highly sensitive patients. D

There are 2 phases of allergen immunotherapy administration: the initial build-up phase, when the dose and concentration of allergen immunotherapy extract are increased, and the maintenance phase, when the patient receives an effective therapeutic dose over a period of time. If the

Supervising medical personnel

Summary Statement 62: Regardless of the location, allergen immunotherapy should be administered under the direct supervision of an appropriately trained physician, qualified physician extender (nurse practitioner or physician assistant), or both in a facility with the appropriate equipment, medications, and personnel to treat anaphylaxis. D

The physician and personnel administering immunotherapy should be aware of the technical aspects of this procedure and have available appropriately trained

Specific allergens

Summary Statement 70: Immunotherapy is effective for pollen, animal allergens, dust mite, mold/fungi, and Hymenoptera hypersensitivity. Therefore immunotherapy should be considered as part of the management program in patients who have symptoms related to exposure to these allergens, as supported by the presence of specific IgE antibodies. A

Noninjection routes of immunotherapy

Summary Statement 92: Allergen extracts can be administered through several routes in addition to the subcutaneous route. Currently, there are no FDA-approved formulations for a noninjection immunotherapy extract. A

Favorable results have been reported with intranasal,431 intrabronchial,432 sublingual,433, 434, 435 oral,436 intralymphatic,437 and epicutaneous438 administration. With intranasal and intrabronchial allergen administration, local symptoms were decreased by use of pretreatment with

Novel formulations: Allergoids and adjuvants

Summary Statement 100: Allergoids are modified allergen extracts processed in a way that reduces the extract’s allergenicity while preserving its antigenicity. B

Allergoids are chemically modified extracts that reduce IgE-binding capacity. These extracts potentially reduce the allergenicity of the allergens but retain antigenicity. However, one study comparing the tolerability of a standardized grass pollen extract with an allergoid reported a higher percentage of systemic reactions in the

Authors’ note

Examples of allergen immunotherapy prescription and administration forms, immunotherapy labels, conventional and cluster build-up schedules, immunotherapy dose adjustments for unscheduled gaps in allergen immunotherapy injection intervals, summaries of documentation guidelines, systemic reaction reporting sheets, and patterns of allergen cross-reactivity can be found in the tables and figures in this article’s Online Repository at www.jacionline.org. Some of these forms, along with examples of

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    Disclosure of potential conflict of interest: L. Cox is a consultant for Genentech/Novartis, Hollister-Stier, and Stallergenes; is a speaker for Novartis; has received research support from Stallergenes; is on the Board of Directors for the American Board of Allergy and Immunology; and is on the US Food and Drug Administration (FDA)’s Allergenic Product Advisory Committee. H. Nelson is a consultant for Merck and Planet Biopharmaceuticals, is a Data and Safety Monitoring Board member of DBV Technologies, and has received research support from ALK-Abelló. M. Nelson has received research support from the Department of Defense, is a speaker for the American College of Allergy, Asthma & Immunology (ACAAI), and is a member of the FDA’s Advisory Committee on Allergic Products. R. Weber is on the speakers’ bureau for AstraZeneca and Genentech, has received research support from Novartis and GlaxoSmithKline, and is Committee Chair of the ACAAI. D. I. Bernstein is a consultant and on the advisory board for ALK America, is on the advisory board for Merck, and has received research support from Merck and Schering-Plough. J. Blessing-Moore is a speaker for Merck-Schering/AstraZeneca, Novartis, TEVA, and Meda Alcon and has received research support from Meda. D. A. Khan is a speaker for AstraZeneca and Merck, has received research support from the Vanberg Family Foundation and the Sellars Family Foundation, is Conjoint Board Review Chair for the ACAAI, and is a past president of the Texas Allergy, Asthma and Immunology Society. D. M. Lang is a speaker and consultant for GlaxoSmithKline; is a speaker for AstraZeneca, Merck, TEVA, Sanofi-Aventis, and Genentech/Novartis; and has received research support from Genentech/Novartis. R. A. Nicklas is a fellow for the ACAAI. J. Oppenheimer is a consultant and has provided lectures for AstraZeneca, Merck, and GlaxoSmithKline; and has received research support from AstraZeneca, Merck, GlaxoSmithKline, and Genentech. J. M. Portnoy is a speaker for Phadia, Merck, and CSL Behring; has received research support from the US Department of Housing and Urban Development; and is a board member of the ACAAI board of regents. S. L. Spector has received research support from Genentech, GlaxoSmithKline, Schering-Plough, Aventis, Novartis, Pharmaxis, Boehringer Ingelheim, AstraZeneca, Johnson & Johnson, Xyzal, Alcon, Centocor, Sepracor, UCB, Amgen, Capnia, and IVAX. S. Tilles is a speaker for Alcon; is on the advisory board for ALK, Ista, Merck, and Stallergenes; has received research support from Alcon, Amgen, Amphastar, Astellas, Boehringer Ingelheim, Ception, Genentech, Icagen, MAP Pharma, MEDA, Merck, Novartis, Roxane, and Sepracor; is Associate Editor of Allergy Watch and Annals of Allergy; and is a task force member for the Joint Task Force for Practice Parameters. D. Wallace is a speaker and advisor for Alcon, is a speaker for Merck and Sanofi-Aventis, and is President-Elect of the ACAAI. The rest of the authors have declared that they have no conflict of interest.

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