19 sep Efficacy of a House Dust Mite Sublingual Allergen
The house dust mite (HDM) sublingual allergen immunotherapy (SLIT) tablet is
a potential novel treatment option for HDM allergy–related asthma.
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reduced by 50% for 3 months and then completely withdrawn for 3 months.
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, and0.69 [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 and0.10 (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, and0.64 [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.
TRIAL REGISTRATION clinicaltrialsregister.eu Identifier: 2010-018621-19.
JAMA. 2016;315(16):1715-1725. doi:10.1001/jama.2016.3964