Efficacy of a House Dust Mite Sublingual Allergen Immunotherapy Tablet in Adults With Allergic Asthma: A Randomized Clinical Trial

TY - JOUR

T1 - Efficacy of a House Dust Mite Sublingual Allergen Immunotherapy Tablet in Adults With Allergic Asthma

T2 - A Randomized Clinical Trial

AU - Virchow, Johann Christian

AU - Backer, Vibeke

AU - Kuna, Piotr

AU - Prieto, Jose Luis

AU - Nolte, Hendrik

AU - Villesen, Hanne Hedegaard

AU - Ljørring, Christian

AU - Riis, Bente

AU - de Blay, Frederic

PY - 2016/4/26

Y1 - 2016/4/26

N2 - IMPORTANCE: The house dust mite (HDM) sublingual allergen immunotherapy (SLIT) tablet is a potential novel treatment option for HDM allergy-related asthma. OBJECTIVES To evaluate the efficacy and adverse events of the HDM SLIT tablet vs placebo for asthma exacerbations during an inhaled corticosteroid (ICS) reduction period. DESIGN, SETTINGS, AND PARTICIPANTS: Double-blind, randomized, placebo-controlled trial conducted between August 2011 and April 2013 in 109 European trial sites. The trial included 834 adults with HDM allergy-related asthma not well controlled by ICS or combination products, and with HDM allergy-related rhinitis. Key exclusion criteria were FEV1 less than 70%of predicted value or hospitalization due to asthma within 3 months before randomization. Efficacy was assessed during the last 6 months of the trial when ICS was reduced by 50% for 3 months and then completely withdrawn for 3 months. INTERVENTIONS: 1:1:1 randomization to once-daily treatment with placebo (n = 277) or HDM SLIT tablet (dosage groups: 6 SQ-HDM [n = 275] or 12 SQ-HDM [n = 282]) in addition to ICS and the short-acting β2-agonist salbutamol. MAIN OUTCOMES AND MEASURES: Primary outcomewas time to first moderate or severe asthma exacerbation during the ICS reduction period. Secondary outcomes were deterioration in asthma symptoms, change in allergen-specific immunoglobulin G4 (IgG4), change in asthma control or asthma quality-of-life questionnaires, and adverse events. RESULTS: Among 834 randomized patients (mean age, 33 years [range, 17-83];women, 48%), 693 completed the study. The 6SQ-HDMand 12SQ-HDMdoses both significantly reduced the risk of a moderate or severe asthma exacerbation compared with placebo (hazard ratio [HR]:0.72 [95%CI, 0.52-0.99] for the 6SQ-HDMgroup, P =.045, and 0.69 [95%CI, 0.50-0.96] for the 12 SQ-HDMgroup, P =.03). The absolute risk differences based on the observed data (full analysis set) in the active groups vs the placebo groupwere0.09 (95%CI, 0.01-0.15) for the 6SQ-HDM group and 0.10 (95%CI, 0.02-0.16) for the 12SQ-HDMgroup. Therewas no significant difference between the 2 active groups. Compared with placebo, therewas a reduced risk of an exacerbation with deterioration in asthma symptoms (HR, 0.72 [95%CI, 0.49-1.02] for the 6SQ-HDM group, P =.11, and 0.64 [95%CI, 0.42-0.96] for the 12SQ-HDMgroup, P =.03) and a significant increase in allergen-specific IgG4. However, therewas no significant difference for change in asthma control questionnaire or asthma quality-of-life questionnaire for either dose. Therewere no reports of severe systemic allergic reactions. The most frequent adverse eventswere mild to moderate oral pruritus (13%for the 6SQ-HDMgroup, 20%for the 12SQ-HDMgroup, and 3%for the placebo group), mouth edema, and throat irritation. CONCLUSIONS AND RELEVANCE: Among adults with HDM allergy-related asthma not well controlled by ICS, the addition of HDM SLIT to maintenance medications improved time to first moderate or severe asthma exacerbation during ICS reduction, with an estimated absolute reduction at 6 months of 9 to 10 percentage points; the reduction was primarily due to an effect on moderate exacerbations. Treatment-related adverse events were common at both active doses. Further studies are needed to assess long-term efficacy and safety.

AB - IMPORTANCE: The house dust mite (HDM) sublingual allergen immunotherapy (SLIT) tablet is a potential novel treatment option for HDM allergy-related asthma. OBJECTIVES To evaluate the efficacy and adverse events of the HDM SLIT tablet vs placebo for asthma exacerbations during an inhaled corticosteroid (ICS) reduction period. DESIGN, SETTINGS, AND PARTICIPANTS: Double-blind, randomized, placebo-controlled trial conducted between August 2011 and April 2013 in 109 European trial sites. The trial included 834 adults with HDM allergy-related asthma not well controlled by ICS or combination products, and with HDM allergy-related rhinitis. Key exclusion criteria were FEV1 less than 70%of predicted value or hospitalization due to asthma within 3 months before randomization. Efficacy was assessed during the last 6 months of the trial when ICS was reduced by 50% for 3 months and then completely withdrawn for 3 months. INTERVENTIONS: 1:1:1 randomization to once-daily treatment with placebo (n = 277) or HDM SLIT tablet (dosage groups: 6 SQ-HDM [n = 275] or 12 SQ-HDM [n = 282]) in addition to ICS and the short-acting β2-agonist salbutamol. MAIN OUTCOMES AND MEASURES: Primary outcomewas time to first moderate or severe asthma exacerbation during the ICS reduction period. Secondary outcomes were deterioration in asthma symptoms, change in allergen-specific immunoglobulin G4 (IgG4), change in asthma control or asthma quality-of-life questionnaires, and adverse events. RESULTS: Among 834 randomized patients (mean age, 33 years [range, 17-83];women, 48%), 693 completed the study. The 6SQ-HDMand 12SQ-HDMdoses both significantly reduced the risk of a moderate or severe asthma exacerbation compared with placebo (hazard ratio [HR]:0.72 [95%CI, 0.52-0.99] for the 6SQ-HDMgroup, P =.045, and 0.69 [95%CI, 0.50-0.96] for the 12 SQ-HDMgroup, P =.03). The absolute risk differences based on the observed data (full analysis set) in the active groups vs the placebo groupwere0.09 (95%CI, 0.01-0.15) for the 6SQ-HDM group and 0.10 (95%CI, 0.02-0.16) for the 12SQ-HDMgroup. Therewas no significant difference between the 2 active groups. Compared with placebo, therewas a reduced risk of an exacerbation with deterioration in asthma symptoms (HR, 0.72 [95%CI, 0.49-1.02] for the 6SQ-HDM group, P =.11, and 0.64 [95%CI, 0.42-0.96] for the 12SQ-HDMgroup, P =.03) and a significant increase in allergen-specific IgG4. However, therewas no significant difference for change in asthma control questionnaire or asthma quality-of-life questionnaire for either dose. Therewere no reports of severe systemic allergic reactions. The most frequent adverse eventswere mild to moderate oral pruritus (13%for the 6SQ-HDMgroup, 20%for the 12SQ-HDMgroup, and 3%for the placebo group), mouth edema, and throat irritation. CONCLUSIONS AND RELEVANCE: Among adults with HDM allergy-related asthma not well controlled by ICS, the addition of HDM SLIT to maintenance medications improved time to first moderate or severe asthma exacerbation during ICS reduction, with an estimated absolute reduction at 6 months of 9 to 10 percentage points; the reduction was primarily due to an effect on moderate exacerbations. Treatment-related adverse events were common at both active doses. Further studies are needed to assess long-term efficacy and safety.

KW - Administration, Inhalation

KW - Administration, Sublingual

KW - Adolescent

KW - Adrenal Cortex Hormones

KW - Adrenergic beta-2 Receptor Agonists

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Albuterol

KW - Allergens

KW - Animals

KW - Antigens, Dermatophagoides

KW - Asthma

KW - Disease Progression

KW - Double-Blind Method

KW - Dust

KW - Female

KW - Humans

KW - Immunoglobulin G

KW - Immunotherapy

KW - Male

KW - Middle Aged

KW - Pyroglyphidae

KW - Quality of Life

KW - Rhinitis

KW - Surveys and Questionnaires

KW - Tablets

KW - Treatment Outcome

KW - Young Adult

KW - Journal Article

KW - Multicenter Study

KW - Randomized Controlled Trial

KW - Research Support, Non-U.S. Gov't

U2 - 10.1001/jama.2016.3964

DO - 10.1001/jama.2016.3964

M3 - Journal article

C2 - 27115376

SN - 0098-7484

VL - 315

SP - 1715

EP - 1725

JO - J A M A: The Journal of the American Medical Association

JF - J A M A: The Journal of the American Medical Association

IS - 16

ER -