Sublingual immunotherapy lengthened the time to first moderate or severe exacerbation during a period of corticosteroid reduction among patients with house dust mite–related asthma, according to a multicenter randomized study published in the April 26 issue of JAMA.
The study reported an estimated absolute reduction at 6 months of 9 to 10 percentage points, mainly as a result of the mitigation of moderate exacerbations. Sensitization to dust mite allergen is present in as many as 50% of patients with asthma, and exposure to it has been linked to asthma severity.
Researchers led by pneumologist J. Christian Virchow, MD, from the Department of Pulmonology/Intensive Care Medicine at the University of Rostock in Germany, conducted the double-blind, randomized, placebo-controlled trial between August 2011 and April 2013 at 109 European sites. The study population consisted of 834 adults (mean age, 33 years; 48% women; 99% Caucasian) with poorly controlled house dust mite allergy–related asthma and allergic rhinitis. Patients with severe unstable asthma were excluded.
Participants were randomly assigned to one of three groups: placebo (277 patients) and two different doses of sublingual tablet, with biological activity expressed in standardized quality house dust mite units (SQ-HDM): 6 SQ-HDM (275 patients) or 12 SQ-HDM (282 patients). Participants placed one tablet under the tongue daily and received treatment for a maximum of 18 months. In addition, the patients used inhaled corticosteroids and the short-acting β2 agonist salbutamol.
During the final 6 months of the study, corticosteroids were reduced by 50% for 3 months and then withdrawn for 3 months. Patients recorded symptoms, medication use, and lung function twice a day in electronic diaries.
Evaluating efficacy during this period in the 693 patients completing the study, the researchers note that both active doses significantly reduced the odds of moderate or severe asthma exacerbation, which was the primary endpoint, compared with placebo. Specifically, the hazard ratios were 0.72 (95% confidence interval [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 in the intervention groups vs in 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. No significant difference was observed between the active groups (hazard ratio, 0.96; 95% CI, 0.68 - 1.37; P = .84).
The treatment groups also showed a significant rise in allergen-specific immunoglobulin 4 antibody, a key secondary outcome. However, the authors saw no significant changes in the Asthma Control or Asthma Quality-of-Life questionnaires with either active dose.
"To our knowledge, this is the first controlled trial to show that adult patients with [house dust mite] allergy-related asthma who were not well controlled taking [inhaled corticosteroids] can achieve an improvement in asthma control as measured by time to first asthma exacerbation with a sublingual tablet formulation of [house dust mite] allergen immunotherapy," Dr Virchow and coauthors write.
Although there were no deaths, anaphylactic episodes, or severe systemic allergic reactions, adverse events were common at both active doses, with the most frequent being mild to moderate oral pruritus of 13% and 20%, respectively, for the 6 and 12 SQ-HDM groups vs 3% for placebo. Oral edema and pharyngeal irritation also occurred. The authors estimated the cost of 3 years of sublingual immunotherapy at about $3400.
"Further studies are needed to assess long-term efficacy and safety," the authors write.
In a related editorial, Robert A. Wood, MD, from the Division of Allergy and Immunology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, notes that several recent studies have yielded positive results for the efficacy of sublingual immunotherapy with house dust mite allergen for asthma and allergic rhinitis.
Dr Wood points out that although sublingual therapy is currently approved in Europe for many allergens, in the United States, the US Food and Drug Administration has approved its use only for five-grass pollen, Timothy grass pollen, and ragweed pollen tablets.
He calls the current study "a valuable contribution to the literature," especially for its focus on a globally significant asthma allergen and its relevant clinical endpoints, but notes that additional rigorous studies of all forms of immunotherapy are still needed.
"The work should not end here, as there is still a great deal of room for refinement in the practice of immunotherapy," Dr Wood writes. "As research continues and these therapies enter clinical practice, the goal should be to optimize each patient's immunotherapy regimen and disease control, taking personal preferences into account, and ideally to develop additional patient profiling using specific biomarkers to further personalize the use of these treatment options."
The trial was sponsored by ALK, Denmark, whose employees had some involvement in the study's design and conduct. Dr Virchow reports receiving grant funding from Deutsche Forschungsgemeinschaft, Land Mecklenburg-Vorpommern, GlaxoSmithKline, Merck Sharp & Dohme; honoraria from Allergopharma, ALK, Chiesi, AstraZeneca, Avontec, Bayer, Bencard, Berlin-Chemie, Bionorica, Boehringer Ingelheim, Essex/Schering-Plough, GlaxoSmithKline, Janssen-Cilag, Kyorin, Leti, Meda, Merck/Merck Sharp & Dohme, Mundipharma, Novartis, Nycomed/Altana, Pfizer, Revotar, Sandoz-Hexal, Stallergenes Greer, Takeda, Teva, UCB/Schwarz Pharma, Zydus/Cadila; and serving on advisory boards for ALK, Asche Chiesi, Avontec, Berlin-Chemie, Boehringer Ingelheim, Essex/Schering-Plough, GlaxoSmithKline, Janssen-Cilag, Merck Sharp & Dohme/Merck, Mundipharma, Novartis, Revotar, Sandoz-Hexal, UCB/Schwarz-Pharma, Takeda. Several coauthors have disclosed various financial relationships with industry in the form of grants, personal fees, honoraria, or advisory board service. Dr Wood reports receiving grant funding from the National Institutes of Health, DBV Technologies, and the Immune Tolerance Network and personal fees from Stallergenes, Sanofi, and UpToDate.
JAMA. 2016;315:1715-1725. Article abstract, Editorial extract
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Cite this: Sublingual Immunotherapy Improves Dust Mite Allergy - Medscape - Apr 27, 2016.
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