Published Online: March 4, 2014
Based on a retrospective survey spanning the experience of North American allergists between 1990 and 2001, one fatal reaction to subcutaneous allergen immunotherapy (SCIT) occurred in every 2 to 2.5 million injection events, or 3.4 SCIT-related deaths per year. In response to these tragic events, updated practice guidelines issued by the Joint Task Force on Practice Parameters have included expert recommendations aimed at preventing SCIT fatalities. To assess the impact of these guidelines on clinical practice and to monitor treatment-related adverse events, the AAAAI/ACAAI annual surveillance program was initiated in 2008. This surveillance program has since served as a registry for physician reports of fatal and non-fatal systemic allergic reactions (SRs) to SCIT and skin testing. In addition, the surveillance project assesses the impact of specific clinical practices related to the administration of SCIT on modifying the risk of severe SRs.
In an article recently published in The Journal of Allergy and Clinical Immunology: In Practice, Epstein and colleagues summarized findings from the first four years of this study (2008-2012). All physician members of the AAAAI and ACAAI (3,919 SCIT-prescribers) were surveyed, and a single respondent was identified for multi-member practices to report the annual experience of his or her practice, each year, beginning on July 1, 2008 and ending on August 31, 2012.
Each year, physician respondents were asked to complete web-based surveys to report SRs of various severity grades, as well as strategies used to minimize reactions in their practice. Participants were also queried regarding fatal reactions to SCIT and skin testing that had occurred in other local practices. For all non-fatal events reported during Years 1-3 (2008-2011), a grading system that included three grades (Grade 1=Mild; Grade 2=Moderate; Grade 3=Severe) of SRs was used. For Year 4 (2011-2012), a shortened version of the World Allergy Organization grading system was adopted, which includes four severity grades (Grade 1=Mild; Grade 2=Moderate; Grade 3=Severe; Grade 4=Very Severe).
Participation in the survey peaked at 806 practices (1,922 SCIT-prescribers, or 49% of potential respondents) in Year 1, and declined to 630 practices (1,453 prescribers; 37% potential respondents) in Year 2, 513 practices (1,072 prescribers; 27% potential respondents) in Year 3, and 402 practices (1,073 prescribers; 27% potential respondents) in Year 4.
During the first four years of the study, data were gathered from 23.3 million injection visits. Only one confirmed injection-related fatal reaction was directly confirmed between 2008 and 2012. Systemic reactions from SCIT were reported in 82-85% of practices, and occurred in one in 1,000 (0.1%) injection visits. Despite variability in response rates, and a change in the grading system for 2011-2012, the rates of SRs of different severity grades was very similar across all four years. There were 9.4 SRs per 10,000 injection visits annually for Years 1-4 including 6.6/10,000 injection visits as Grade 1 (mild) SRs, 2.6/10,000 injection visits as Grade 2 SRs (moderate), and 0.4/10,000 injection visits as Grade 3 SRs (severe). Grade 4 life-threatening SRs were only recorded in Year 4; one Grade 4 SR was estimated to occur in every 1 million injection visits. Almost one-third of practices experienced at least one SR to allergy skin testing, but none reported severe Grade 3 or 4 SRs from skin testing. Cluster build-up, an accelerated build-up strategy, was associated with higher rates of SRs overall. Lowering doses during pollen seasons was significantly associated with lower rates of Grade 3 and 4 SRs in both maintenance and build-up vials.
SR rates have remained stable and the rate of fatal reactions to SCIT may be declining, but a high degree of vigilance, and continued study regarding risk factors for severe and fatal SRs is necessary. Further study regarding strategies to minimize risks associated with accelerated build-up regimens is warranted. Lowering doses in maintenance and build-up vials during pollen seasons appears to lower risks, but optimal algorithms and the impact of dose adjustment on efficacy have yet to be determined.
The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.