Dose-Dependent Clinical and Immunological Efficacy of Sublingual Immunotherapy with Mite Monomeric Allergoid

Abstract

Sublingual immunotherapy with monomeric carbamylated allergoid (LAIS) is an effective and well tolerated treatment of respiratory allergy. The aim of the present study was to correlate the efficacy of two maintenance doses (1000 AU vs 3000 AU) of LAIS with the immunological modulation of allergendriven Thl, Th2 and T regulatory cytokines produced in vitro by PBMCs, in patients suffering from mite allergic rhinitis. Forty-eight consecutive patients with mite allergic rhinitis were recruited. Patients were randomly assigned to group A (n=24) or group B (n=24), respectively receiving 1000 AU or 3000 AU weekly during one-year maintenance phase. Each patient was evaluated for rhinitis severity (ARIA protocol), and for drug consumption at the time ofthe inclusion and after 6 and 12 months oftreatment. Patients were also asked to report the perceived severity of the disease and the tolerability of the treatment in a visual analogical scale (VAS). Before and at the end of the treatment allergen-driven release of cytokines by PBMCs in vitro was measured. After J-year treatment, a statistically significant reduction of all clinical parameters was observed in all patients, associated with reduction of IL-4 and increase of INF-y secreted in vitro by mite-challenged PBMCs. Notably, the group treated with the higher dose showed significantly better clinical and immunological results. The efficacy of LAIS is correlated to the immune modulation in a clear dose-dependent effect.Sublingual specific immunotherapy with monomeric carbamylated allergoid (LAlS) is an effective and well tolerated treatment of respiratory allergy (1-5). The monomeric allergoid was obtained by carbamylation of the allergen with potassium cyanate at alkaline pH, a reaction that leads to a substantial substitution of the s-amino groups of the lysine residues within the protein. This simple chemical modification confers to the allergoid a series ofcharacteristics (6) which made it particularly appropriate for sublingual administration. Among them,thehypoallergenicity andthemonomericity, that

A 12-week DBPC dose-finding study with sublingual monomeric allergoid tablets in house dust mite-allergic patients

“…The favourable safety profile in this study corresponds to that observed in other studies and has been confirmed in a meta‐analysis . SLIT studies using native allergens are often confounded by the high rate of local side‐effects in the actively treated groups that may unblind patient and investigator.…”

“…During the treatment phase of 84 days, the patients received daily dosages of a placebo preparation or one of four different active strengths: 300 UA/day, 1000 UA/day, 2000 UA/day or 3000 UA/day (cumulative doses for the 84 days of treatment were 25 200–252 000 UA). According to a publication by Di Gioacchino, 1000 UA correspond to 2.7 μg of group 1 mite allergen and 3000 UA to 8.1 μg of group 1 mite allergen .…”

The Impact on Allergy-Related Cells of a Birch Pollen Allergoid, with and without Monophosphoryl Lipid A, in Comparison with the Native Equivalent

“…The rapid impact of allergoids on in vitro cytokine responses outside of ongoing SIT have remained ill-defined, as the common approach is to assess such responses in PBMCs before/after SIT, a strategy that precludes the comparison of different antigen preparations on the same subject. In studies investigating SIT, increases in IL-10 and IFNγ [13,14] and decreases in IL-4 were described [14] . In our study, the cytokine responses showed substantial variability among the donors, and not all allergic individuals were responsive to either allergen or allergoid in this setting.…”

Sublingual Immunotherapy Tablets Relieve Symptoms in Adults with Allergic Rhinitis

“…[ 22 ] In addition, SLIT tablets ensure better modulation of the drug amount and higher compliance than SLIT drops due to its safety and convenience for transportation, administration, and follow-up. [ 23 ] A majority of current RCTs showed some benefit from immunotherapy on RQLQ and RTSS. SCIT and SLIT are two forms of immunotherapy on allergic rhinitis while SLIT has proven to be potentially safer than SCIT.…”