A Double-Blind Placebo-Controlled Evaluation of Sublingual Immunotherapy with a Standardized Ragweed Extract in Patients with Seasonal Rhinitis

Abstract

Background: There is a growing consensus on the benefits of sublingual-swallow immunotherapy in the treatment of allergic diseases. Methods: This randomized, double-blind placebo-controlled study was undertaken to assess the efficacy and safety of sublingual immunotherapy with standardized ragweed pollen extract tablets, in patients with an allergic rhinitis. A total of 110 outpatients were randomized (immunotherapy [I]: 55; placebo [P]: 55), of whom 99 were analyzable for efficacy (I: 48; P: 51) and 106 analyzable for safety (I: 53; P: 53). After a 28-day progression phase, the patients received a maintenance treatment during 6.5 months. Efficacy variables included a global assessment of efficacy (patient/ investigator), symptoms and medication scores as well as the frequency of asthma attacks. Results: In the active treatment group, 43 patients completed the study, versus 49 on placebo. During the whole period of pollination, the difference favoring immunotherapy was highly significant for the global assessment by the patient (p = 0.004) and by the investigator (p = 0.005). Adverse reactions were reported more often in the active treatment but mild or moderate, and they abated after dose adjustment. A subgroup analysis of those patients receiving the highest dose of immunotherapy (3 tablets 3 times a week) showed a highly significant response for rhinitis and conjunctivitis total scores by comparison to lower dosages. Conclusion: This study confirms the efficacy and safety of sublingual immunotherapy and strongly suggests a dose-response relationship.

Lack of Detectable Alterations in Immune Responses during Sublingual Immunotherapy in Children with Seasonal Allergic Rhinoconjunctivitis to Grass Pollen

“…One study on adults with SAR treated with different doses SLIT strongly suggests a dose-response relationship also for SLIT, since patients receiving the highest doses showed a significantly greater symptom score reduction than those with lower dosages [25]. However, since the dosage was not predefined and adjusted to the patients’ tolerance, the results have to be treated with some caution.…”

Heat denaturation, a simple method to improve the immunotherapeutic potential of allergens

“…This further illustrates the dichotomy between epitopes bound by different isotypes, and suggests that heatdenatured allergens could also be useful in SIT in humans. Moreover, it allows the use of higher therapeutic doses, which per se is known to promote Th1 immune responses [40,41] and to be favourable in combating allergic immunopathology [15,16].…”

“…Another strategy is to increase safety and tolerability of SIT by injecting the allergen in a form that is not recognised by IgE, such as naked DNA vaccines expressing the allergen [8]. Recombinant DNA technology has also allowed the production of mutated allergens with low IgE-binding capacity [9][10][11][12][13][14], such that higher therapeutic doses can be used [15,16]. For the same reasons, short, synthetic peptide sequences corresponding to T cell epitopes from the allergen have been used for SIT.…”

“…This further illustrates the dichotomy between epitopes bound by different isotypes, and suggests that heatdenatured allergens could also be useful in SIT in humans. Moreover, it allows the use of higher therapeutic doses, which per se is known to promote Th1 immune responses [40,41] and to be favourable in combating allergic immunopathology [15,16].In conclusion, heat-denatured allergen extracts show reduced IgE binding and therefore would increase the safety and tolerability of SIT. Yet surprisingly, heat denaturation of allergen extracts enhanced production of the Th1-dependent IgG2a subclass, which worked therapeutically in allergic mice.…”

Immunological Effects of Sublingual Immunotherapy: Clinical Efficacy Is Associated with Modulation of Programmed Cell Death Ligand 1, IL-10, and IgG4

“…Thus, SLIT results in a dosedependent increase of allergen-specific IgG4 (24,29), even if this effect is less intensive than that induced by SCIT (26,27,(30)(31)(32) and mostly evident for seasonal aeroallergen. SLIT also reduces mucosa infiltration by effector cells (neutrophils and eosinophils) (33), increases allergen-specific IL-10 production (34)(35)(36), and modulates Th1 and Treg activity in the oral mucosa (37)(38)(39)(40)(41)(42)(43).…”