Efficacy of a House Dust Mite Sublingual Allergen Immunotherapy Tablet in Adults With Allergic Asthma: A Randomized Clinical Trial.
OBJECTIVE
The house dust mite (HDM) sublingual allergen immunotherapy (SLIT) tablet is a potential novel treatment option for HDM allergy-related asthma.


OBJECTIVE
To evaluate the efficacy and adverse events of the HDM SLIT tablet vs placebo for asthma exacerbations during an inhaled corticosteroid (ICS) reduction period.


METHODS
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was assessed during the last 6 months of the trial when ICS was reduced by 50% for 3 months and then completely withdrawn for 3 months.


METHODS
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.


METHODS
Primary outcome was 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 6 SQ-HDM and 12 SQ-HDM doses 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 6 SQ-HDM group, P = .045, and 0.69 [95% CI, 0.50-0.96] for the 12 SQ-HDM group, P = .03). The absolute risk differences based on the observed data (full analysis set) in the active groups vs the placebo group were 0.09 (95% CI, 0.01-0.15) for the 6 SQ-HDM group and 0.10 (95% CI, 0.02-0.16) for the 12 SQ-HDM group. There was no significant difference between the 2 active groups. Compared with placebo, there was a reduced risk of an exacerbation with deterioration in asthma symptoms (HR, 0.72 [95% CI, 0.49-1.02] for the 6 SQ-HDM group, P = .11, and 0.64 [95% CI, 0.42-0.96] for the 12 SQ-HDM group, P = .03) and a significant increase in allergen-specific IgG4. However, there was no significant difference for change in asthma control questionnaire or asthma quality-of-life questionnaire for either dose. There were no reports of severe systemic allergic reactions. The most frequent adverse events were mild to moderate oral pruritus (13% for the 6 SQ-HDM group, 20% for the 12 SQ-HDM group, and 3% for the placebo group), mouth edema, and throat irritation.


CONCLUSIONS
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.


BACKGROUND
clinicaltrialsregister.eu Identifier: 2010-018621-19.
Department of Pneumology/Intensive Care Medicine, University of Rostock, Germany.
J Christian
JC
Virchow
Department of Respiratory Medicine, Bispebjerg University Hospital, Copenhagen, Denmark.
Vibeke
V
Backer
Division of Internal Medicine, Asthma and Allergy, Medical University of Lodz, Poland.
Piotr
P
Kuna
Departamento de Medicina, Universidad de Valencia, Spain.
Luis
L
Prieto
Merck Research Laboratories, White House Station, New Jersey.
Hendrik
H
Nolte
Global Clinical Development, ALK, Hoersholm, Denmark.
Hanne Hedegaard
HH
Villesen
Global Clinical Development, ALK, Hoersholm, Denmark.
Christian
C
Ljørring
Global Clinical Development, ALK, Hoersholm, Denmark.
Bente
B
Riis
Chest Disease Department, University Hospital of Strasbourg, Strasbourg University, France.
Frederic
F
de Blay
D000280:Administration, Inhalation; D000286:Administration, Sublingual; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D058666:Adrenergic beta-2 Receptor Agonists / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000420:Albuterol / Q000627:therapeutic use; D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D018450:Disease Progression; D004311:Double-Blind Method; D004391:Dust; D005260:Female; D006801:Humans; D007074:Immunoglobulin G; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D039981:Pyroglyphidae / Q000276:immunology*; D011788:Quality of Life; D012220:Rhinitis / Q000188:drug therapy* / Q000276:immunology; D011795:Surveys and Questionnaires; D013607:Tablets; D016896:Treatment Outcome; D055815:Young Adult
D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D000485:Allergens; D039741:Antigens, Dermatophagoides; D004391:Dust; D007074:Immunoglobulin G; D013607:Tablets; D000420:Albuterol