Immunotherapy: An Update

Immunotherapy (Desensitisation): An Update

Immunotherapy has been adopted as the best term to denote the slow immunizing process of injecting allergenic extracts in ascending doses, which causes increased tolerance to develop to the injected substance. It has come a long way since first used in 1911 by Noon, an English doctor. He administered crude grass pollen extracts to patients with hay fever and noted reduction in their symptoms. Recent advances in immunotherapy have depended on the improved understanding of IgE-mediated diseases, the characterization of specific antigens and the standardization of allergen extracts.

Several randomized studies have shown that it is a very effective and safe treatment for allergic rhinitis, allergic asthma and anaphylaxis to insect venom.

Immunotherapy has been reported by Timothy Sullivan, MD, from Emory University Atlanta, to be "considerably less expensive than pharmacological treatment for asthma and allergic rhinitis", based on a comparitive economic analysis.

The annual cost of pharmacotherapy for moderate to severe asthma was estimated at $1,000 per year, and for allergic rhinitis, approximately $1,200. Allergen immunotherapy is estimated at $800 for the initial year and $170 to $290 for each subsequent year of maintenance therapy (depending on the number of antigens involved).

Summary Statements from the draft manuscript Allergen Immunotherapy: A Practise Parameter presented at the Allergen Immunotherapy Symposium at the AAAA&I 58th Annual Meeting in New York March 1-6 2002

The joint Task Force on Practise Parameters, representing the American Academy of Allergy, Asthma and Immunology, the American College of Allergy, Asthma and Immunology, and the Joint Council of Allergy, Asthma and Immunology developed the parameters.

Editors:
James T. Li , M/D.
Richard F. Lockey, M.D.
Jay M. Portnoy, M.D.
Leonard Bernstein, M.D.
Richard A. Nicklas, M.D.

Classification of Recommendations and Evidence

  Category of Evidence
Ia Evidence from meta-analysis of randomised controlled trials
Ib Evidence from at least 1 randomised controlled trial
IIa Evidence from at least 1 controlled study without randomization
11b Evidence from at least 1 other type of quasi-experimental study
III Evidence from non-experimental descriptive studies, such as comparative studies, correlation studies and case-control studies
IV Evidence from expert committee reports or clinical experience of respected authors or both.

  Strength of Recommendation
A Directly based on category I evidence
B Directly based on category II evidence or extrapolated recommendation from category I evidence
C Directly based on category III evidence or extrapolated recommendation from category I or II evidence
D Directly based on category IV evidence or extrapolated recommendation from I, II or III evidence
NR Not rated
 

Draft Summary Statements

(Of the 69 draft summary statements available, only the statements considered of interest to New Zealand doctors and patients are included below)

MECHANISMS OF IMMUNOTHERAPY

  • Immunologic changes during immunotherapy are complex. Successful immunotherapy is associated with a shift from Th2 to Th1 CD4+ lymphocyte immune response to allergen. (A)
  • Successful immunotherapy is also associated with immunologic tolerance, defined as a relative decline in allergen specific responsiveness. (A)
  • Efficacy from immunotherapy is not dependent on reduction in Specific IgE levels. (A)
  • Rises in allergen specific IgG blocking antibody titre are not predictive of the duration and degree of efficacy of immunotherapy. (A)

ALLERGENIC EXTRACTS/VACCINES

  • Standardised extracts/vaccines should be used whenever possible to prepare extract/vaccine treatment sets. (A)
  • Non-standardised extracts may vary widely in biologic activity. (B)
  • In choosing the components for a clinically relevant extract/vaccine, the physician should be familiar with local and regional aerobiology with regards to both indoor and outdoor allergens with special attention to potential allergens in the patients' own environment. (D)
  • Knowledge of allergen cross-reactivity is extremely important in the selection of allergens for immunotherapy because limiting the number of allergens in the treatment vial is necessary to attain optimal therapeutic doses for the individual patient. (B)

EFFICACY OF IMMUNOTHERAPY

  • Immunotherapy is effective for treatment of allergic rhinitis, allergic asthma, and stinging insect hypersensitivity . Therefore, immunotherapy merits consideration in patients with these disorders as a possible treatment option. (A)
  • Clinical studies do not support the use of immunotherapy for food hypersensitivity or chronic urticaria and/or angioedema. Therefore, allergen immunotherapy for patients with food hypersensitivity or chronic urticaria and/or angioedema is not recommended. (D) There is limited data indicating that immunotherapy may be effective for atopic dermatitis when this condition is associated with aeroallergen sensitivity. (C)
  • At this time, clinical parameters, such as symptom scores and medication use may be useful measures of the efficacy of immunotherapy in a clinical setting.However routine periodic testing of patients on immunotherapy is not recommended. (A)

SAFETY OF IMMUNOTHERAPY

  • Severe systemic reactions following allergen immunotherapy in the USA are rare when allergen immunotherapy is appropriately administered. (C)
  • Since most systemic reactions that result from allergen immunotherapy occur 20-30 minutes after an injection, patients should wait at least 30 minutes following an injection. (D)
  • Patients receiving beta-adrenergic blocking drugs may be at increased risk when receiving allergen immunotherapy because blockade of beta-receptors can make the treatment of anaphylaxis more difficult. Therefore, if possible, immunotherapy should not be initiated or continued in patients receiving beta-blockers, unless benefits and risks are considered and discussed with the patient. (C)
  • Alternatives to allergen immunotherapy should be considered in patients with any medical condition that reduces the patient's ability to survive a systemic reaction, such as:

    1. Severe asthma uncontrolled by drugs

    2. Significant cardiovascular disease that increases the risk of sequelae from anaphylaxis or side effects from treatment, in particular, adrenaline. (C)
  • Allergen immunotherapy should be administered in a setting where procedures are in place that can reduce the risk of anaphylaxis, and where the prompt recognition and treatment of anaphylaxis is assured. (D)

PATIENT SELECTION

  • Allergen immunotherapy should be considered for patients who have demonstrable evidence of specific IgE antibodies to clinically relevant allergens ( positive skin prick test or modified RAST ). The decision to begin immunotherapy depends on the degree to which symptoms can be reduced by avoidance and medication, the amount and type of medication required to control symptoms, and the adverse effects of medications.
  • Allergen immunotherapy in Asthmatic patients should not be initiated unless the patient's asthma is stable with drug therapy.
  • Venom immunotherapy (VIT) should strongly be considered if the patient has had a systemic reaction to a Hymenoptera sting, especially if such a reaction was associated with respiratory and/or cardiovascular symptoms, and if the patient has positive skin tests for specific IgE antibodies. (A)
  • Patients selected for immunotherapy should be cooperative and compliant. (D)

IMMUNOTHERAPY SCHEDULES AND DOSES

  • Commercially available allergen extracts may be used alone or combined to produce an individual patient's customised allergen mixture. (D)
  • The dose of the extract/vaccine should be appropriately reduced following a systemic reaction if immunotherapy is continued. (D)
  • It is customary to reduce the dose of extract when the interval between injections is prolonged. (D)
  • Rush schedules can achieve a maintenance dose more quickly than weekly schedules (A)
  • To reduce the rate of systemic reactions, pre-medication should be given prior to rush immunotherapy. (B)
  • Once a patient reaches a maintenance dose, the interval between injections often can be progressively increased as tolerated up to an interval of 4 to 6 weeks. (A)
  • Patients should be re-evaluated at least every 6-12 months while they receive immunotherapy. (D)
  • A decision about continuation or stopping immunotherapy should be made after 3-5 years. (D)

SPECIAL CONSIDERATIONS IN IMMUNOTHERAPY

  • The preferred location for administration of allergen immunotherapy is in the office of the physician who prepared the patient's vaccine. (D)
  • Regardless of the location, allergen immunotherapy should be administered under the supervision of an appropriately trained physician and personnel. (D)
  • Immunotherapy for children is effective and often well tolerated. Therefore, immunotherapy should be considered, (along with drug therapy and allergen avoidance) in the management of children with allergic rhinitis, allergic asthma, and stinging insect hypersensitivity. (A)
  • Children under 5 years of age can have difficulty cooperating with an immunotherapy program. Therefore, the physician who evaluates the patient must consider the benefits and risks of immunotherapy and individualise treatment in patients less than 5 years. (A)
  • Allergen immunotherapy may be continued but is usually not initiated in the pregnant patient. (C)
  • Comorbid medical conditions and certain medication use may increase the risk of immunotherapy in elderly patients. Therefore, special consideration must be given to the benefits and risks of immunotherapy in this patient population.
  • Immunotherapy can be considered in patients with immunodeficiency and autoimmune disorders.
  • Optimal high dose sublingual swallow and oral immunotherapies are under evaluation, but these modalities are not currently used in the US. Oral immunotherapy should be considered investigational at this time. (B)
  • Low dose immunotherapy, enzyme-potentiated immunotherapy and immunotherapy (parenteral or sublingual) based on provocation-neutralization testing are not recommended. (D)
  • Immunotherapy with a different extract/vaccine should be given cautiously. If, as is often the case, there is inadequate information to support continuing with the previous immunotherapy program, reevaluation may be necessary and a new schedule and extract prepared. (D)

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