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Wise et al.

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contraindications were partially controlled asthma, autoimmune diseases in remission, cardiovascular disease, and use of beta-adrenergic blocking agents. The Allergy Immunotherapy: Practice Parameters 3rd Update, on the other hand, found no substantive evidence that immunotherapy is harmful in patients with autoimmune diseases. 1623 The Practice Parameters also list pregnancy as a contraindication to initiating SCIT. 1623 It may, however, be continued if the patient is on maintenance dosing. Extracts.: In the United States, most pollen, dander, insect, and fungal extracts are available either in a buffered saline with phenol or in 50% glycerin. The exception is those extracts that have been standardized by the FDA which only come in 50% glycerin. There is 1 line of alum-precipitated extracts, consisting solely of pollen extracts. In Europe, on the other hand, alum-precipitated extracts are commonly employed and there is increasing use of allergoid extracts consisting of natural allergens partially denatured by mixture with an aldehyde. 1593,1594,1605,1621,1622,1628 (See sections IX.D.1. Management – Immunotherapy – Allergen extract units, potency, and standardization and IX.D.2. Management – Immunotherapy – Modified allergen extracts for additional information on this topic.) Dosing.: The beneficial results of SCIT have been repeatedly shown to be dependent on administering a sufficient maintenance dose of each extract with each maintenance injection. 1609,1629-1631 Reduction of the effective maintenance dose by 90% to 95% causes partial or complete loss of efficacy. 1632 The results of many double-blind, placebo-controlled studies have been utilized to formulate the recommendations for dosing in Table IX.D.3-2, adapted from the Immunotherapy Practice Parameters 3rd Update. 1623 Monosensitization vs polysensitization.: In most large studies of AR, 80% to 85% of the subjects are sensitized to more than 1 unrelated allergen. Analysis of some of these studies has shown that the polysensitized subjects respond as well to (sublingual) AIT as those with sensitivity only to the administered allergen. 1633 There is no immunological rationale why this should be different in subcutaneous AIT, but this specific question is an important unmet need which should be addressed in future trials. 28,1634 Single-allergen vs multiple-allergen AIT.: It is the common practice among US allergists to include in their treatment multiple allergen extracts to which the patient is sensitized. A recent survey of 670 patients in 6 practices found a mean of 18 allergen extracts in their treatment. 29,1635 On the other hand, European guidelines recommend treating with the single most troublesome allergen identified clinically, 1636 or if more than 1 extract is to be given they should be given at separate sites with at least 30 minutes in between administration. 32 Scientific support for the U.S. allergists’ approach of using multiple allergen mixtures for SCIT can be found in 4 double-blind, placebo controlled studies, 2 in patients with AR, 1629,1637 1 in children with asthma, 1630 and 1 in patients with both rhinitis and asthma, 1638 all of which demonstrated significant improvement in patients receiving mixtures of multiple, unrelated allergen extracts. However, a recent review concluded that multiallergen immunotherapy in polysensitized patients, whether delivered sublingually or subcutaneously, requires more supporting evidence from well-designed, well-powered, double-blind, placebo-controlled clinical trials to validate its efficacy in practice. 1634

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Int Forum Allergy Rhinol . Author manuscript; available in PMC 2020 June 10.