Sublingual immunotherapy for allergic rhinitis and asthma effective, JAMA reports

April 2, 2013

In an examination of a type of treatment for allergic rhinitis and asthma that is used in Europe but not approved by FDA, researchers found moderate strength in the evidence from previous studies to support the use of sublingual immunotherapy for the treatment of these conditions, according to a review article in the March 27 issue of JAMA.

In an examination of a type of treatment for allergic rhinitis and asthma that is used in Europe but not approved by FDA, researchers found moderate strength in the evidence from previous studies to support the use of sublingual immunotherapy for the treatment of these conditions, according to a review article in the March 27 issue of JAMA.

The article identified 63 randomized, controlled studies on sublingual immunotherapy, which involves administration of aqueous allergens under the tongue for local absorption to desensitize the allergic individual over an extended treatment period to diminish allergic symptoms.

Currently approved allergic immunotherapies are administered by subcutaneous injection. Allergic rhinitis (an allergic reaction with symptoms similar to a cold) affects approximately 20% to 40% of the US population. Considerable interest has emerged in the use of sublingual immunotherapy as a treatment.

Researchers at the Johns Hopkins University School of Medicine, Baltimore, and colleagues conducted a systematic review of previous studies to examine the effectiveness and safety of aqueous sublingual immunotherapy for allergic rhinoconjunctivitis and asthma. After a review of the medical literature, Sandra Y. Lin, MD, and colleagues identified 63 studies with 5,131 participants (ranging in age from 4 to 74 years) that met the inclusion criteria for the review. Twenty studies (n=1,814 patients) enrolled only children.

They found strong evidence supporting that sublingual immunotherapy improves asthma symptoms, with 8 of 13 studies reporting greater than 40% improvement versus the comparator. “Moderate evidence supports that sublingual immunotherapy use decreases rhinitis or rhinoconjunctivitis symptoms, with 9 of 36 studies demonstrating greater than 40% improvement versus the comparator,” according to the authors. “Medication use for asthma and allergies decreased by more than 40% in 16 of 41 studies of sublingual immunotherapy with moderate grade evidence. Moderate evidence supports that sublingual immunotherapy improves conjunctivitis symptoms (13 studies), combined symptom and medication scores (20 studies), and disease-specific quality of life (8 studies).”

Evidence was similar in strength to support the use of sublingual immunotherapy in children (<18 years of age) for allergic rhinitis and asthma.

Local reactions were frequent, but there were no reported episodes of anaphylaxis, life-threatening reactions, or death in any treated patients across studies.

“Our review found moderate strength in the evidence to support the use of sublingual immunotherapy for allergic rhinitis and asthma. This indicates moderate confidence that the evidence reflects a true efficacy. However, future research could change the estimate. High-quality studies are needed to answer questions of optimal dosing strategies,” the authors concluded.

In an accompanying editorial, Harold S. Nelson, MD, of National Jewish Health, Denver, wrote that “although the publication of many studies has been reassuring regarding issues of efficacy and safety of sublingual immunotherapy, as reported by Lin et al, several concerns regarding use of sublingual immunotherapy in the United States remain.”

“There are no extracts licensed by [FDA] available for sublingual administration of immunotherapy. In the absence of any product for which appropriate dosing and safety have been established in the United States, there is no Current Procedural Terminology code for administering sublingual immunotherapy to patients in the United States.”

“Until sublingual immunotherapy gains FDA approval, physicians who choose to administer off-label sublingual immunotherapy will have limited guidance in selecting effective dosing. In addition, clinicians should be aware that the evidence for efficacy of sublingual immunotherapy is derived from studies of treatment with a single allergen extract, not with combinations of unrelated allergens.”

While Merck does not market or manufacture allergy drops and did not participate in the recent analysis, Merck spokesperson Tracy Ogden said the company is pleased to see the increased scientific discussion around the opportunity for oral allergy immunotherapy in the United States.

“We agree that high-quality studies are needed determine the safety and efficacy of sublingual immunotherapy,” Ogden said.

Merck has conducted a clinical program for its investigational Timothy grass pollen (Phleum pretense) allergy immunotherapy tablet [AIT]. It is an investigational, dissolvable oral tablet designed to help treat the underlying cause of allergic rhinitis by generating an immune response to help protect against targeted allergens. The Biologics License Application (BLA) for its grass pollen AIT was just accepted for review by FDA and is supported by phase 3 trials that evaluated the safety and efficacy of the investigational product, including a long-term, multiseason trial, according to Ogden.

“If approved, it would represent a potential new option for allergy specialists to offer appropriate allergic rhinitis patients,” she said.