Incidence and risk factors for subcutaneous immunotherapy anaphylaxis: the optimization of safety

Abstract

Fatal reactions related to subcutaneous allergen immunotherapy are rare: one event in 2.5 million injections has been reported in the USA and none in Europe. The prevalence of very severe systemic reactions (systemic adverse events [SAEs]) is one in 1 million injections. Though the serious events rate is decreasing and the majority of SAEs (∼0.2% per injection) are moderate and reversible, they still represent a major concern. Uncontrolled asthma, long-term therapy with β-blockers and high degree of allergen sensitivity are generally considered risk factors. The relevance of other conditions, like previous local reactions, the use of extracts conjugated with adjuvants and accelerated build-up schedules is controversial, as well as the role of preventative strategies. A careful risk assessment of patients and optimal administration procedures may significantly decrease the risk of SAEs. However, more uniform safety data are required and an accurate safety profile should be provided for every allergen product.

Keywords:

• allergen immunotherapy
• anaphylaxis
• local reactions
• risk factor
• safety
• subcutaneous
• systemic reactions

Financial & competing interests disclosure

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. No writing assistance was utilized in the production of this manuscript.

Key issues

• The risk of subcutaneous immunotherapy (SCIT)-related systemic adverse events (SAEs) still represent a major concern that may, sometimes unnecessarily, limit the use of this effective treatment.

• According to real-life surveillance studies, SCIT-related fatal events are rare (one event every 2.5 million injections according to the most recent reports) and a decline in their incidence has been recently observed in the real-life setting. No fatal anaphylaxis has been reported in randomized clinical trials.

• The overall rate of SAEs per injection is approximately 0.2% (range: 0.026–0.37% in the USA and 0.01–0.3% in Europe). A near-fatal event every million injections was reported.

• One major limitation of the studies reporting SCIT safety data is the poor comparability between the provided results, due to substantial differences mainly concerning recording and grading systems, treatment schedules, allergen doses and allergenic products.

• A consensus about risk factors and their management still lacks, particularly concerning local reactions. Prevention strategies based on dose-adjustments and pre-medication with H1 anti-histamines are supported by weak evidences.

• A more standardized approach to SAEs is needed. A more uniform safety data collection is required and an accurate safety profile should be provided for every allergen product in a real-life setting.

• A careful risk assessment of patients and optimal administration procedures may significantly decrease the risk of SCIT-related SAEs.