Subcutaneous Allergen Immunotherapy for Allergic Disease

Examining Efficacy, Safety and Cost-Effectiveness of Current and Novel Formulations

Linda Cox; Moisés Calderón; Oliver Pfaar

Disclosures

Immunotherapy. 2012;4(6):601-616. 

In This Article

Other Indications for SCIT

SCIT is currently indicated for patients with symptoms of AR, rhinoconjunctivitis and/or asthma after natural exposure to allergens who demonstrate specific IgE antibodies to relevant aeroallergens, and patients who have experienced SRs to Hymenoptera and/or imported fire ant stings.[23,32] Factors to consider in the decision to prescribe allergen immunotherapy include the severity and duration of symptoms, response to pharmacotherapy, quality of life and responsiveness to other forms of therapy (e.g., allergen avoidance or medication) and indirect effects of the allergic disease, such as lost time from work or school (see Box 3 for SCIT indications). Although relative contraindications for SCIT may vary according to different guidelines (e.g., pregnancy and β-blockers), virtually all agree that SCIT should be avoided in patients with medical conditions that would reduce their ability to survive a SCIT systemic allergic reaction and/or the resultant treatment.

SCIT for Large Local Venom Reaction: Potential Indication

Although large local insect sting reactions have not been shown to be predictors of future SR, they may cause significant morbidity and impairment of quality of life, particularly in individuals who may experience frequent stings due to their occupation (e.g., beekeeper or landscaper) or avocation (e.g., gardener). One 4 year controlled pilot study suggested that venom immunotherapy (VIT) may significantly reduce the size and duration of large local reactions.[33] In the 29 patients with a history of large local sting reactions (≥16 cm) confirmed on sting challenge who received VIT, there was a 42% reduction in the size and a 53% reduction in the duration of the large local sting reactions after 7–11 weeks of VIT compared with an 18% reduction in both size and duration in the untreated control group (p < 0.01 for both).[33] Further studies are needed to establish the safety and efficacy of VIT for large local reactions, but recent practice guidelines suggest it may be "considered in patients who have frequent and disabling large local reactions, particularly those with occupational exposure" (e.g., beekeepers).[32] Further study would also be needed to evaluate the cost–efficacy and most appropriate patients for VIT directed at treating large local reactions.

SCIT for Atopic Dermatitis: Potential Indication

There are some data indicating that SCIT may be effective for atopic dermatitis when this condition is associated with aeroallergen sensitivity.[34–37] In one systematic review of immunotherapy for atopic dermatitis, SCIT was associated with a statistically significant improvement in dermatitis symptoms in the four comparable placebo-controlled studies.[36] One randomized, double-blind, dose–response study demonstrated a dose-dependent response in atopic dermatitis severity, as measured by the Scoring Atopic Dermatitis (SCORAD) score (p = 0.0378) and topical corticosteroid use (p = 0.0007).[34] In addition, one open-label study demonstrated serological and immunological changes consistent with tolerance, as well as significant reductions in objective and subjective SCORAD scores in dust mite allergic patients with atopic dermatitis.[37]

SCIT for Food Hypersensitivity & Oral Allergy Syndrome

In addition to the above indications, SCIT has been investigated in several other clinical conditions, including food allergy. SCIT provided some clinical tolerance against peanut anaphylaxis with an aqueous peanut extract but was associated with an unacceptable rate of systemic allergic reactions, such that the investigators recommended discontinuation of clinical trials until a modified extract was available.[38] At present, investigations with SCIT for food hypersensitivity have largely been abandoned. However, studies with alternative immunotherapy routes have demonstrated potential efficacy in the treatment of IgE-mediated food reactions. Increased tolerance on food challenge was demonstrated with hazelnut[39] and milk[40] sublingual immunotherapy (SLIT) and with peanut,[41] egg[42,43] and milk[44] oral immunotherapy. In peanut-sensitized mice, epicutaneous immunotherapy was found to be as effective as SCIT in inducing favorable immunological and physiological responses compared with sham-treated mice.[45]

Clinical trials examining the benefits of SCIT for oral allergy syndrome utilizing the cross-reacting pollen(s) have produced conflicting results. One controlled prospective study demonstrated that birch pollen SCIT was effective in decreasing oral allergy symptoms related to apple or hazelnut birch tree.[46] Another double-blind, double-dummy, placebo-controlled study demonstrated no significant effect on the severity of apple allergy symptoms with either birch pollen SCIT or SLIT compared with the placebo group, despite a significant effect of both SIT routes on seasonal hay fever symptoms and medication use as well as a decrease in IgE reactivity.[47] More investigation is required to determine whether SCIT is effective in the treatment of oral allergy symptoms related to cross-reacting pollens.

SCIT for Indications With Limited or No Supporting Evidence for Efficacy and/or Safety: Latex, Urticaria & Angioedema

Clinical trials with SCIT for latex-induced respiratory disease have produced conflicting results in terms of clinical efficacy.[48–50] Moreover, latex SCIT was associated with frequent and severe SRs, including hypotension, compared with placebo treatment.[48,50] At the present, much of the focus of latex immunotherapy has been on the sublingual route, for which there appears to be a more favorable efficacy–safety profile.[51]

There is no allergic basis for the majority of chronic urticaria and angioedema patients or clinical trial evidence to support treatment of these conditions with any route of SIT.[32] Therefore, chronic urticaria and/or angioedema are not considered indications for SIT.

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