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Wise et al.

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cumulative amount administered that determines efficacy, 1646 and no blinded studies have been offered to support the efficacy of this low-dose approach.

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Accelerated SCIT administration.: To shorten the length of the buildup, cluster dosing is sometimes employed. Two or 3 injections are given on each visit on nonconsecutive days, with a 30-minute waiting between injections. If visits are twice weekly, maintenance dosing can be achieved in 4 weeks 1647 or even after a shorter period depending on the product administered and schedule followed. 1648 A retrospective analysis of rates of systemic reactions in a large, multiple-physician practice 1649 and a double-blind randomized trial 1650 showed no increase in the rate of systemic reactions in patients, comparing cluster to conventional regimens. Another (open) trial supports these findings. 1651 Rush regimens administer many injections per day on consecutive days, typically achieving maintenance dosing in 1 to 3 days. Even with the use of premedication, there is an increased rate of systemic reactions compared to conventional dosing. 1652 Mechanism of action.: In general, the immunologic response to SCIT involves 2 sequential steps. The first is a generation of regulatory T-cells secreting IL-10 and TGF- β , leading to a switch from IgE to IgG4 antibody formation. 1653,1654 With continued AIT the Treg response declines and an immune deviation from Th2 to Th1 responses dominates. 1577,1653 (See section IV. Pathophysiology and mechanisms of allergic rhinitis for additional information on this topic.) Modification of disease.: An advantage of SCIT over pharmacotherapy is that it alters the underlying immunologic response towards that which is seen in non-allergic individuals. 1654 The results of this alteration in the underlying immune response by SCIT can be seen clinically in the reduction in new sensitizations, in the progression from AR to asthma, and in the persisting benefit following an adequate course of therapy. In children, adolescents, and young adults, who are sensitized only to the allergen being administered, the development of new sensitizations is reduced not only during AIT but for several years following completion of the course of AIT. 1625,1626 A similar protective effect has not been demonstrated in patients polysensitized at the initiation of AIT. SCIT has also been shown to prevent the progression from AR to asthma. A total of 205 children, sensitized to grass, birch or both, and showing no evidence of asthma during an observational year, were treated with Timothy and/or birch SCIT for 3 years, or standard pharmacotherapy alone, and observed for an additional 7 years after completion of SCIT in an open trial. 1624 The risk for developing asthma was significantly reduced at the end of SCIT and persisted for the 7 years of follow-up. The database of the German National Health Insurance was used to follow patients with AR without asthma who were or were not placed on AIT in 2006. 1655 During a 5-year follow-up, those patients who received AIT (90% on SCIT) were significantly less likely to have developed asthma.

Duration of treatment and persistence of treatment effect.: Regarding persistence of benefit, a double-blind, randomized study was conducted in patients with AR who had

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