The safety of sublingual immunotherapy, can the rare systemic reactions be prevented?

ABSTRACT

Introduction: The safety of subcutaneous immunotherapy (SCIT), and particularly the dramatic issue of fatal reactions, has been an obstacle that limited the implementation of a therapy with unique characteristics of action on the causes of allergy. The introduction of sublingual immunotherapy (SLIT) was aimed at solving safety problems while maintaining clinical efficacy.

Areas covered: For more than 20 years, SLIT has been based on allergen extracts in drops at low average doses. As evidenced by meta-analyses, the typical adverse events (AE) have consisted of local reactions in the mouth and throat. Unlike the injection route, no correlation was observed between the administered dose and AEs. The development of SLIT products in tablets, based on higher doses than drops, has somewhat changed the concept of SLIT safety. Although large trials, performed to obtain regulatory agency approval, have shown overall high safety, rare anaphylactic reactions have been described.

Expert opinion: SLIT is globally safe, and no fatal reactions have ever been reported, but with currently available high biological potency products it is necessary to follow prudential rules, such as the administration of the first dose under medical supervision and the thorough education of patients to avoid taking of higher doses than recommended.

KEYWORDS:

• Allergen immunotherapy
• safety
• local reactions
• systemic reactions
• subcutaneous
• sublingual

Article highlights

• Allergen immunotherapy is the only causal treatment of allergy, but the subcutaneous route was concerned by severe and even fatal reactions.

• The sublingual route has proved to be much safer, adverse reactions occurring in most cases in the mouth and throat, and systemic reactions being rare and not severe.

• From the middle 2000s, a new generation of higher biological potency SLIT products in tablets, including grass, ragweed and Japanese cedar pollen, and dust mites, was introduced.

• With such tablet products, severe adverse reactions, also requiring administration of epinephrine, were reported, but no fatalities occurred, this being of great importance.

• This makes it advisable that precautionary rules be regularly adopted in patients treated with respiratory allergen tablets, mainly if risk factors are present, such as prior severe reactions to SCIT or administration of multiple allergens in poly-sensitized patients.

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Declaration of interest

C Incorvaia has been a scientific consultant for Bayer S.p.A. and Stallergens S.r.I. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have served as a consultant to ALK. All other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This research received no specific grant from any funding agency.