Treating both allergic asthma and allergic rhinitis

In both the MITRA trial and the supporting Phase II clinical trial (MT-02), the efficacy of SQ HDM sublingual immunotherapy (SLIT)-tablets in HDM allergic patients was demonstrated. In the MITRA trial, treatment with the 12-SQ HDM SLIT-tablet resulted in a 34% relative risk reduction (P=0.017) in moderate-to-severe asthma exacerbations during ICS reduction when compared to placebo. The overall result was supported by reductions across the key components of the primary endpoint:

• Nocturnal awakening or increase in symptoms
• Increased short-acting beta agonist (SABA) use
• Deterioration in lung function
• Severe asthma exacerbations

The MITRA trial showed a 34% reduced risk of moderate-to-severe asthma exacerbations.

Please note that in the first assessment period, day 1-90, ICS was reduced 50%. In the second assessment period, day 91-180, ICS was reduced 100%.

The evidence for SQ HDM SLIT-tablets from the MITRA trial is supported by a dose-finding Phase II trial (MT-02). In the MT-02 trial, patients were treated with 3 different doses of SQ HDM SLIT-tablet. In the highest dose arm of the study, patients were treated with a once-daily 6-SQ HDM SLIT-tablet and were able to significantly reduce their daily use of ICS compared to placebo. At the 4-week, end-of-trial, efficacy evaluation period, the mean change from baseline in the daily ICS dose was 207.6 µg budesonide in the 6 SQ-HDM group compared to 126.3 µg in the placebo group. In a post-hoc analysis of a subgroup (N=108) of subjects with lower asthma control and ICS ≥400 µg budesonide, the mean change from baseline in the daily ICS dose was 384.4 µg budesonide in the 6 SQ-HDM group and 57.8 µg in the placebo group, corresponding to an absolute difference between 6 SQ-HDM and placebo of 327 µg budesonide per day (95% CI [182;471], p<0.0001).

The MT-02 showed that SQ HDM SLIT-tablet enables ICS reduction while maintaining control.

The efficacy of SQ HDM SLIT-tablets in HDM allergic asthma was demonstrated in the large, double-blind, randomised, placebo-controlled Phase III study known as the MITRA trial, and further supported by the Phase II study MT-02.

The MITRA trial included adults with HDM allergic asthma that was not well-controlled by daily use of ICS (400-1200 µg budesonide). All patients received 7-12 months’ treatment with SQ HDM SLIT-tablets or placebo, in addition to ICS and SABA. Efficacy was assessed by the time to the first moderate or severe asthma exacerbation during ICS reduction over the last 6 months of 13-18 months of treatment. The Phase II study (MT-02) included patients older than 14 years of age with HDM allergic asthma controlled by inhaled ICS (100-800 µg budesonide). At the 4-week, end-of-trial, efficacy evaluation period, the mean change from baseline in the daily ICS dose was assessed.

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The efficacy of SQ HDM SLIT-tablets in HDM allergic rhinitis was investigated in two double-blind, randomised, placebo-controlled Phase III trials conducted in Europe and North America, respectively. In addition, supporting evidence from an allergen exposure chamber Phase II trial is described.

The primary endpoint in the 2 Phase III trials for allergic rhinitis was the total combined rhinitis score (TCRS), i.e., the sum of the rhinitis symptom score and the rhinitis medication score. TCRS was assessed during the last 8 weeks of treatment. In the MERIT trial, a relative difference in TCRS of 22% was demonstrated when compared to placebo, the difference was statistically significant (P=0.001). Similar efficacy was demonstrated in the North American study P001, and for the adolescent subgroup, where a relative difference of 22% (p=0.024) compared to placebo was found. The adolescent results from P001 were further substantiated by data from a trial conducted in 278 Japanese adolescents (TO-203-3-2 study).

Additionally, the Phase II chamber study, P003, allowed for further evaluation of the onset of efficacy of the 12 SQ-HDM SLIT-tablet. In the study, a statistically significant reduction in total nasal symptom score (TNSS) of 20% (P=0.007) compared to placebo was already apparent from week 8. After 24 weeks the TNSS improvement relative to placebo was 49% (P<0.001).

Analyses of the TCRS are based on medians.

Patients taking SQ HDM SLIT-tablets should primarily expect mild-to-moderate local allergic reactions to occur within the first few days and subsiding again with continued treatment (1-3 months). For the majority of events, the reaction should be expected to start within 5 minutes after intake of SQ HDM SLIT-tablets on each day of occurrence and abate within a timeframe ranging from minutes to hours. More severe oropharyngeal allergic reactions may occur. Reported adverse reactions in adolescents have been similar in frequency, type and severity to those seen in adults.

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Virchow et al. “Efficacy of a House Dust Mite Sublingual Allergen Immunotherapy Tablet in Adults With Allergic AsthmaA Randomized Clinical Trial” JAMA. 2016;315(16):1715–25. DOI: 10.1001/jama.2016.3964

Mosbech et al. “Standardized quality (SQ) house dust mite sublingual immunotherapy tablet (ALK) reduces inhaled corticosteroid use while maintaining asthma control: A randomized, double-blind, placebo-controlled trial” J Allergy Clin Immunol. 2014;134(3):568-575. DOI: 10.1016/j.jaci.2014.03.019

Nolte et al. “Onset and dose-related efficacy of house dust mite sublingual immunotherapy tablets in an environmental exposure chamber” J Allergy Clin Immunol. 2015;135(6):1494-501. DOI: 10.1016/j.jaci.2014.12.1911

Nolte et al. “Efficacy of house dust mite sublingual immunotherapy tablet in North American adolescents and adults in a randomized, placebo-controlled trial” J Allergy Clin Immunol. 2016 Dec;138(6):1631. DOI: 10.1016/j.jaci.2016.06.044