D3.225 - Two years Sublingual SQ-Grass Pollen Tablet Immunotherapy Combined with Dupilumab Induces Longterm Suppression of Immediate Cutaneous Allergen Sensitivity

We performed a randomised double-blind placebo-controlled trial to evaluate the induction of durable clinical tolerance one year after two years treatment with the combination of sublingual grass pollen tablet immunotherapy (SLIT) and dupilumab. We assessed cutaneous immediate allergen sensitivity by use of immediate skin prick test titration as a surrogate marker of clinical response.

108 participants with moderate-severe grass pollen seasonal allergic rhinoconjunctivitis were randomised to one of three arms and treated: SLIT/dupilumab (grass SLIT-tablet 75,000 SQ-T plus dupilumab), SLIT (grass SLIT-tablet 75,000 SQ-T plus dupilumab-placebo), or double-placebo. Skin prick endpoint titration tests were performed at baseline and annually for two years during treatment and one year after treatment discontinuation. Skin tests were performed in duplicate and reverse order on the flexor aspect of the forearms, with incremental log increasing doses of Timothy grass pollen (Phleum Pratense) extract ranging from 0.001 to 10 Histamine Equivalent Prick (HEP) units/mL. Immediate cutaneous allergen sensitivity was interpolated from the duplicate dose-response curves (minus the saline negative control skin test) as the mean provocation concentration of Phleum Pratense extract that caused a 5 mm skin wheal (PC5).

At year 3, one year after completing 2 years’ treatment SLIT/dupilumab resulted in a marked increase in PC5 Least Square geometric mean (95% CI) of 4.62 (2.30,9.31) HEP U/mL compared with placebo 0.062 (0.031, 0.12) and compared with SLIT alone 0.540 (0.258,1.134) representing a 75.6-fold (27.4, 202.7) increase in the LS geometric mean compared with placebo (p<0.001)  and an 8.56-fold (3.10, 23.64) increase compared with SLIT alone (p<0.001). The LS geometric mean fold increase for SLIT alone compared with placebo was 8.71 (3.10, 24.47) (p<0.001). PC5 data at baseline and after years 1, 2 and 3 for the three treatment arms are shown in the figure.

Two years combination therapy with SLIT/dupilumab resulted in marked suppression of immediate cutaneous allergen sensitivity as determined by titration allergen skin testing compared with both SLIT alone and placebo treatment. The effect persisted for one year after treatment discontinuation; results are supportive of induction of long-term allergen tolerance.