title: Safety and immunological changes during sublingual immunotherapy with standardized quality grass allergen tablets.
abstract: Immunotherapy is the only treatment for allergy that has the potential to alter the natural course of the disease. Sublingual immunotherapy for grass pollen-induced rhinoconjunctivitis has been developed to make immunotherapy available to a broader group of allergic patients. Here, a safe dose range and the safety during daily sublingual administration were investigated for a new tablet-based sublingual immunotherapy for grass pollen allergy. Simultaneously, immunological changes were monitored. A randomized, double-blind, placebo-controlled phase I trial was undertaken, with stepwise dose-escalation during the dose-finding period, and afterwards with daily dosing 8 weeks prior to and 15 weeks during the grass pollen season (2500, 25000, or 75000 standardized quality tablet [SQ-T] units, or placebo). Fifty-two participants with grass pollen-induced rhinoconjunctivitis and a positive skin prick test and specific IgE to Phleum pratense entered the trial. During the daily-dose treatment periods, 67% of the participants reported adverse events. The most frequent were itching in the mouth, eyes, or throat, and rhinitis, and most were mild and resolved within 1 day. Two participants withdrew due to adverse events (sting and blisters in the mouth and itching in the mouth). Time- and dose-dependent increases of P pratense-specific IgG, IgA, IgE, and IgE-competing components were found in serum during the first 8 weeks of daily dosing, indicating that the treatment had a significant allergen-specific effect on the immune system. In conclusion, the grass allergen tablet, administered in a dose of 75000 SQ-T once daily, was well tolerated and displayed systemic immunogenicity.
authors.affiliation: Allergy Clinic, National University Hospital, Copenhagen, Denmark. hans.joergen.malling@rh.hosp.dk
authors.forename: H J
authors.initials: HJ
authors.lastname: Malling
authors.forename: L
authors.initials: L
authors.lastname: Lund
authors.forename: H
authors.initials: H
authors.lastname: Ipsen
authors.forename: L
authors.initials: L
authors.lastname: Poulsen
mesh_terms: D000284:Administration, Oral; D000286:Administration, Sublingual; D000293:Adolescent; D000328:Adult; D000368:Aged; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy; D007136:Immunoglobulins / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D008875:Middle Aged; D006109:Poaceae / Q000276:immunology*; D011058:Pollen / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000628:therapy*; D013607:Tablets; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000485:Allergens; D007136:Immunoglobulins; D013607:Tablets