Grass pollen sublingual immunotherapy for seasonal rhinoconjunctivitis: a randomized controlled trial

Background Previous studies suggest that sublingual immunotherapy (SLIT) represents a safer alternative to injection immunotherapy but equivalent efficacy is yet to be confirmed. Objective To evaluate the efficacy and safety of SLIT in grass pollen-induced seasonal rhinoconjunctivitis. Methods A randomized, placebo-controlled trial in 56 adults over 18 months. Outcome measures included diary scores of seasonal symptoms and medication use, overall assessments, conjunctival and intradermal provocation tests and serum antibody measurements. To investigate possible mechanisms, sublingual biopsies were taken for measurement of local T cells, antigen-presenting cells and IL-12 mRNA expression. Results There were no significant differences between the mimunotherapy (IT) and placebo groups for diary symptom scores (P = 0.48) or rescue medication (P = 0.19). The patients' overall assessment of hayfever severity compared with previous years showed a highly significant improvement in favour of the IT group (P < 0.02). After treatment the late skin response was smaller (P = 0.003) and the ratio of serum allergen-specific IgG4/IgE was higher (P = 0.05) in the IT group. Both of these variables correlated with the clinical response to SLIT. There were no differences between groups in either the sublingual epithelium or lamina propria for numbers of CD3(+) cells (epithelium: P = 0.9. lamina propria: P = 0.2), CD1a(+) cells (P = 0.3, P = 0.25), CD68(+) cells (P = 0.9 P = 1.0) or IL-12 mRNA(+) cells (P = 0.6, P = 0.4). Local side-effects were minor and there were no serious treatment-related adverse events. Conclusion Grass pollen sublingual immunotherapy was well tolerated. Although there was no significant change in diary scores, the improvement in overall assessments, which correlated with inhibition of the late skin response and increases in serum IgG4: IgE ratio, indicates the need for larger, dose-ranging studies.