Immunotherapy Safety: What Have We Learned from Surveillance Surveys?

Abstract

Subcutaneous allergen immunotherapy (SCIT) is beneficial for the treatment of allergic rhinitis, asthma, and in preventing stinging insect anaphylaxis, but is not without risks. Four retrospective surveillance surveys and one on-going national prospective study have attempted to characterize the incidence and risk factors for fatal and non-fatal SCIT reactions. These studies have contributed significantly to currently recommended SCIT safety guidelines. Recent surveillance studies indicate stable SR rates, and a possible decline in the incidence of fatal reactions since the implementation of evidence-based safety guidelines. This review will provide a detailed summary of the evidence from surveillance studies for risk factors associated with SCIT reactions, including: uncontrolled asthma, prior systemic reactions, dosing during peak pollen seasons, epinephrine being delayed or not given, dosing or administration errors, inadequate waiting times, reactions occurring more than 30 min after injections, injections given in medically unsupervised settings, concomitant beta-blocker and angiotensin-converting enzyme inhibitor (ACEi) use, and accelerated build-up regimens.

An Unusual, Delayed, Localized Bullous Reaction After Subcutaneous Allergen Immunotherapy

“…1,2 It is important to exclude extrinsic factors (eg, physical exercise, 1 One limitation to our case report is that no biopsy was performed, which may have been helpful in elucidating a mechanism. There is a previous report of delayed localized urticaria after receiving SCIT.…”

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

“…This trend could be related to an increased awareness of the potential risk factors, such as asthma, comorbidities, concomitant pharmacological treatments, increased seasonal allergen load, accelerated build-up schedules and type of allergen [33]. Though the evidences for their clinical relevance are not always strong, an accurate assessment of the patient profile and the choice of a proper administration protocol certainly improve the treatment safety [2,3,6,[33][34][35][36].…”

“…Recent major clinical studies could clearly reveal that cluster schedules with both (semi-)depot-allergen preparations and chemically modified allergen preparations ('allergoids') are well-tolerated therapeutic options in SCIT and their safety profile is similar to the safety profile of conventional buildup schedules (TABLE 4). Moreover, the role of accelerated buildup protocols should be considered also in the light of the potential 'increasing risk' effect of a higher number of administrations in conventional protocols, giving the fact that the allergen dose itself cannot be considered a risk factor [36]. More importantly, as some of the reported fatalities occurred when SCIT was administered at home [2], physician expertise and proper administration setting could significantly impact on the other identified administration-related risk factors.…”

Chinese Guideline on allergen immunotherapy for allergic rhinitis

“…Other potential risk factors for SCIT-related SRs, such as administration during the height of the pollen season, build-up dosing schedule (cluster vs. conventional), and treatment phase (maintenance vs. build-up phase) have been suggested, but none have been clearly established (249). However, some risk factors for severe adverse effects and fatal events are shown in Table 6 (250)(251)(252)(253).…”