Published Online: December 16, 2013
Fall marks the start of seasonal allergy misery for millions of ragweed sufferers. Most turn to treatment with symptomatic relief medications (e.g., antihistamines and decongestants) often in conjunction with a controller agent (e.g., topical nasal steroid) that must be used religiously, otherwise benefit is lost once the preparation is discontinued. In contrast, subcutaneous immunotherapy (SCIT) is a disease-modifying treatment; however, many patients refuse or become non-compliant with SCIT, either out of discomfort associated with injections, the need for frequent office visits interfering with their schedules, or the risk of systemic allergic reactions.
In this experimental study published in The Journal of Allergy and Clinical Immunology (JACI) Creticos et al report the first successful confirmatory clinical trial to demonstrate the tolerability and effectiveness of a standardized ragweed extract administered as a sublingual liquid allergen extract as opposed to a subcutaneous injection.
In this randomized, double-blind, placebo-controlled trial, study subjects were randomly assigned to treatment with a sublingual allergen immunotherapy liquid extract of ragweed (RW-SAIL) or placebo. Treatment was initiated 8-16 weeks prior to the ragweed pollen season and patients administered daily drops through the ragweed season. Treatment was given at the clinical investigator’s research site on the first day of treatment, but all subsequent doses were self-administered by the patient at home.
The study patients recorded their seasonal symptoms on electronic diaries, and the Total Combined Score (TCS), which was the defined primary efficacy outcome for the study, was clearly improved in the subjects that received active treatment (RW-SAIL) versus placebo. This TCS was improved 43% for the patients receiving RW-SAIL versus placebo. The expected up-regulation of protective IgG4 antibody, a biomarker that has been shown to be associated with improvement in symptoms and medication use, provides reassurance that the treatment dose was adequate.
The safety findings from the study showed that treatment with the sublingual allergen immunotherapy liquid extract was well-tolerated (94% of patients maintained the target dose; e.g., ~50 mcg Amb a 1) with the frequency of adverse events similar for both treatment groups with the exception of treatment-related oral mucosal local application-site reactions which were transient and self-limited and more frequent in the active treatment group. No systemic allergic reactions, anaphylaxis, or life-threatening events occurred in the study, and few patients discontinued the study due to an adverse event.
Sublingual ragweed immunotherapy appears to offer a safe, convenient, and effective form of treatment for management of patients afflicted with ragweed-induced seasonal allergic rhinoconjunctivitis with or without milder asthma. This study takes on major significance in the U.S., as the off-label use of sublingual aqueous extracts is increasing, but only limited data from well designed and properly powered safety and dose-exploring efficacy studies exist to support this use.
The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.