The REPEAT study: recognizing and evaluating periodic local reactions in allergen immunotherapy and associated systemic reactions

Background: prior studies have demonstrated that large local reactions (LLRs) to subcutaneous immunotherapy do not predict systemic reactions (SRs). However, a recent study demonstrated an increase in LLRs among systemic reactors in practices using routine local reaction dose adjustments.

Objective: to investigate the association between LLRs and SRs within a practice that does not dose adjust for LLRs.

Methods: we performed a retrospective analysis of an electronic immunotherapy database during a 12-month period at a single site that does not dose adjust for LLRs. An LLR was defined as larger than the size of the patient's palm measured at 30 minutes. Logistic regression was performed to investigate the association between SRs and LLRs after controlling for variable numbers of injections and visits among patients.

Results: three hundred sixty patients received a total of 9,679 injections (6,609 visits). Twenty-four patients (6.7% of patients) experienced 38 LLRs (0.4% of injections, 0.6% of visits), whereas 46 patients (12.7% of patients) experienced 51 SRs (0.5% of injections, 0.77% of visits). Only 10 patients (2.8%) experienced both LLRs and SRs, and 36 of 46 SR patients (78.3%) never had an LLR. Among the 24 LLR patients, the SR rate was 1.3% (12/932) of injections and 2.0% (12/611) of visits compared with the 336 non-LLR patients for whom the SR rate was 0.4% (39/8,747) of injections and 0.7% (39/5998) of visits. Of these 24 LLR patients, 10 (41.7%) experienced at least 1 SR vs 36 of 336 non-LLR patients (10.7%). After controlling for number of injections and 1 vs 2 injections per visit, a subgroup of LLR patients were more likely to have an SR during their subcutaneous immunotherapy course (odds ratio, 4.7; 95% confidence interval, 1.9-11.7). Recurrent LLR patients (n = 10) were not more likely to experience an SR (0.4% per injection).

Conclusions: although LLRs do not predict SRs, a subgroup (41.7%) of LLR patients experience a higher frequency of SRs during their immunotherapy course. In light of a similar previous study, this association occurs irrespective of whether a dose adjustment protocol is used for LLRs.