Small Bites of Allergy and Immunology: Rapid 2-step refill protocol vs standard immunotherapy dosing

At the American College of Allergy, Asthma & Immunology Annual Scientific Meeting in Orlando, Florida, investigators from Cleveland Clinic Children’s Hospital presented data comparing 2 refill protocols for subcutaneous immunotherapy (SCIT) for aeroallergens. The study evaluated whether a rapid 2-step cluster protocol differed in safety from the traditional multivisit dose-reduction approach when initiating a new maintenance vial.

When new maintenance vials are prepared, clinicians often reduce doses and rebuild over several visits because higher allergen concentrations may increase the risk of systemic reactions. As described in the presentation, “in the multi-visit standard dosing protocol, we typically scale back when we start a new maintenance file and build back up over three or four doses…in order to decrease the incidence of systemic reaction.”

The alternative protocol consisted of a same-day cluster approach. “The rapid two step or cluster dosing consists of 0.25 MLS given in two separate injections between 30 minutes on one visit.” This allows patients to return to a 0.5 mL maintenance dose in a single visit.

The investigators conducted an IRB-approved retrospective review of 477 pediatric and adult charts across multiple Cleveland Clinic sites. They examined patient age, asthma and eczema status, prior history of systemic reactions, and the incidence and severity of reactions during the study period.

Among the 477 patients, there were 10 systemic reactions. Six occurred in the multivisit standard arm and four in the rapid 2-step arm. The overall incidence of systemic reaction per injection was 0.7% in both groups. In the standard protocol, reactions were distributed across grades 1 through 3. In the rapid arm, 3 reactions were grade 3 and 1 was grade 4. The grade 4 reaction occurred in a patient who had exercised immediately before injection, a known risk factor for systemic reactions.

Because of the low number of events, the study was not adequately powered to detect small differences between protocols. However, the authors reported “no evidence of an increased rate of systemic reaction in the rapid two step build up protocol versus the multi visit standard protocol.” A prior history of systemic reaction was the most statistically significant covariate associated with subsequent reactions; asthma, eczema, and age were not statistically significant in this cohort.

Investigators plan to expand chart review to increase statistical power and to assess adherence to the recommended minimum 3 years of SCIT. A single-visit refill strategy may reduce office visits and support treatment continuation, with potential implications for long-term outcomes in allergic disease.