Onset and dose-related efficacy of house dust mite sublingual immunotherapy tablets in an environmental exposure chamber

• Published in: Journal of allergy and clinical immunology Vol. 135; no. 6; pp. 1494 - 1501.e6
• Main Authors: Nolte, Hendrik, Maloney, Jennifer, Nelson, Harold S., Bernstein, David I., Lu, Susan, Li, Ziliang, Kaur, Amarjot, Zieglmayer, Petra, Zieglmayer, René, Lemell, Patrick, Horak, Friedrich
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2015; Elsevier Limited
• Subjects: Adolescent; Adult; Allergen immunotherapy; Allergens - administration & dosage; Allergens - immunology; allergic rhinoconjunctivitis; Allergies; Allergy and Immunology; Animals; Antigens, Dermatophagoides - administration & dosage; Antigens, Dermatophagoides - immunology; Asthma - complications; Asthma - immunology; Asthma - physiopathology; Asthma - therapy; Atmosphere Exposure Chambers; Compliance; Conjunctivitis - complications; Conjunctivitis - immunology; Conjunctivitis - physiopathology; Conjunctivitis - therapy; Dermatophagoides pteronyssinus; Dermatophagoides pteronyssinus - chemistry; Dermatophagoides pteronyssinus - immunology; dose related; dose response; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug dosages; environmental exposure chamber; Female; house dust mite; Humans; Immunotherapy; Male; Middle Aged; nasal symptoms; ocular symptoms; onset of action; Pyroglyphidae - immunology; Rhinitis, Allergic - complications; Rhinitis, Allergic - immunology; Rhinitis, Allergic - physiopathology; Rhinitis, Allergic - therapy; Studies; Sublingual Immunotherapy; sublingual immunotherapy tablet; Tablets; Time Factors; Treatment Outcome; allergic rhinoconjunctivitis; VAS; environmental exposure chamber; HDM; ocular symptoms; DU; dose response; nasal symptoms; dose related; SCIT; EEC; SLIT; house dust mite; AE; onset of action; MID; RQLQ(S)12; AR; sublingual immunotherapy tablet; AAR; TSS; VCC; AR/C; Allergen immunotherapy; TOSS; TNSS; Vienna Challenge Chamber; Developmental units; Total symptom score; Visual analog scale; Total ocular symptom score; Active anterior rhinomanometry; Allergic rhinitis; Rhinoconjunctivitis Quality of Life Questionnaire with Standardized Activities for subjects ≥12 years old; Allergic rhinitis with or without conjunctivitis; Adverse event; Subcutaneous immunotherapy; Sublingual immunotherapy; Total nasal symptom score; Minimally important difference
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2014.12.1911

The magnitude of effect of sublingual immunotherapy for house dust mite (HDM)–induced allergic rhinitis with or without conjunctivitis is uncertain, partly because there are few well-controlled trials with well-defined doses. We sought to determine the dose-related efficacy and onset of action of the HDM sublingual immunotherapy tablet MK-8237 (Merck/ALK-Abelló) using the Vienna Challenge Chamber. In this randomized, double-blind, single-site trial, adults with HDM-induced allergic rhinitis with or without conjunctivitis and with or without asthma (n = 124) received 12 developmental units (DU) of MK-8237, 6 DU of MK-8237, or placebo daily for 24 weeks. Subjects underwent 6-hour exposure challenges at screening and weeks 8, 16, and 24. The total nasal symptom score (TNSS) during chamber challenge at week 24 was the primary end point. The TNSS was the sum of 4 nasal symptom scores (maximum = 12). Total ocular symptom scores (TOSSs; 2 symptoms; maximum = 6) and total symptom scores (TSSs; TSS = TNSS plus TOSS; maximum = 18) were secondary end points. Dose- and time-dependent improvements with MK-8237 versus placebo were observed. At week 24, TNSS improvement relative to placebo was 48.6% (95% CI, 35.3% to 60.2%) with 12 DU of MK-8237 and 26.6% (95% CI, 11.2% to 39.6%) with 6 DU of MK-8237. Statistically significant improvements for TNSSs were also observed at weeks 8 (12 DU of MK-8237) and 16 (6 and 12 DU of MK-8237) and for TOSSs and TSSs by both doses at week 24. MK-8237 was well tolerated. No investigator-assessed anaphylactic allergic reactions or reactions requiring epinephrine were observed. MK-8237, 12 DU, reduced nasal and ocular symptoms and exceeded World Allergy Organization–established clinical efficacy criteria (≥20% improvement vs placebo). The onset of action for 12 DU of MK-8237 was week 8. MK-8237, 12 DU, is appropriate for further evaluation to determine the magnitude of effect in an uncontrolled allergen exposure environment.