Clinical Efficacy, Safety and Dosing Regimens in Sublingual Immunotherapy

Comparing safety and efficacy between sublingual immunotherapy and subcutaneous immunotherapy.

During the American Academy of Allergy, Asthma and Immunology’s 2015 annual conference in Houston, TX, Linda Cox, MD, discussed the latest clinical findings in sublingual immunotherapy (SLIT). Cox is the chair of the American Academy of Allergy, Asthma and Immunology’s immunotherapy and allergy diagnostics committee.

According to Cox, the efficacy of subcutaneous immunotherapy (SCIT) and SLIT has already been established in innumerous reviews. SLIT has been shown to be an effective treatment for allergic rhinitis/conjunctivitis and asthma. She mentioned; however, that only one well conducted clinical study compared the efficacies of SCIT and SLIT, and that no statistical differences have been detected.

Regulatory cohorts now require the assessment of outcomes during natural season exposure and throughout the year (perennial). The perennial assessment is more challenging because the exposure to allergen is less evident. Cox commented that these difficulties in assessment sometimes prevent the introduction of new SLIT drugs in the US market. In order to overcome this situation, the US is now considering the use of the environmental chamber challenge, which permits the evaluation of the outcomes for specific allergens. According to the World Allergy Organization (WAO), a drug must improve symptoms scores at least 20% to be considered efficient. Nevertheless, several clinical trials use different scoring systems. To prevent discrepancies, the European Academy of Allergy and Clinical Immunology (EAACI) has issued a position on the harmonization of these scores, but it is not clear whether pharmaceutical companies will follow it or not.

Cox then presented a summary of multiple studies that confirmed the efficacy of several anti-allergic medications. Compared to placebo, the magnitude of improvement induced by antihistamines was 8%, 15% for steroids, and 5% for leukotrienes. Another study showed that loratadine caused an improvement of 12%, whereas SCIT improvement reached 35%. In 2014, Nelson and collaborators reviewed a series of opened and double-blind randomized trials to evaluate and compare the efficacy of SLIT and SCIT. Overall, they observed that SCIT had a greater effect over placebo than SLIT. One of the studies, however, concluded that the clinical efficacy of SLIT and SCIT remains to be determined. Cox pointed out that studies to determine the most effective dose for SLIT and SCIT are urgently needed.

Following the presentation of these studies, Cox discussed the safety of SLIT. She told the audience that the side effects of these drugs are generally mild, being local reaction the most frequent. In the UK, two cases of eosinophilic esophagitis have been reported. Recently, it has been reported a case of a child who had systemic reaction after taking oral SLIT together with cereals. Researchers speculated that the reaction was induced by oral abrasions caused by the cereal, and not by the SLIT. In order to help patients and clinicians to follow the status of their reactions, a grading system has been developed to dictate the discontinuation of the treatment or not.

Finally, Cox discussed the use of epinephrine and SLIT. In general, patients receiving SLIT are not prescribed injectable epinephrine in the event of a rare systemic reaction. Additionally, practitioners should be aware of medications that make patients irresponsible to epinephrine. At present, there is no international guidance to tell clinicians what to advise their patients.