High-dose escalation allergen immunotherapy feasible for allergic rhinitis

Accelerated high-dose escalation of allergen immunotherapy (AIT) with a grass pollen allergoid was as safe and tolerable as the standard dose escalation schedule in patients with moderate-to-severe allergic rhinitis or rhinoconjunctivitis with or without comorbid asthma, a study has shown.

“Accelerated dose schedules might offer the opportunity to gain faster clinical and immunological tolerance compared with standard dose escalation,” said the researchers. “We were able to demonstrate that an accelerated high-dose escalation schedule with one strength [of the] grass pollen allergoid can indeed be used in [this setting with] a safety and tolerability profile comparable to the standard escalation schedule.”

The trial was conducted prior to grass pollen season (autumn and winter) in Spain, Poland, Germany, and Russia. Eighty-seven patients (mean age 34.3 years, 55.8 percent male) were randomized 1:1 to receive aluminium hydroxide-adsorbed allergoid preparations of six grass pollen species* either through an accelerated high-dose escalation scheme (10,000 TU/mL administered through three subcutaneous injections**; arm A) or a standard dose escalation schedule (1,000 and 10,000 TU/mL given via seven injections***; arm B). [Int Arch Allergy Immunol 2020;181:94-102]

A majority of participants in arms A and B (82.2 percent and 85.4 percent) reported at least one treatment-emergent adverse event (TEAE). Nearly 60 percent of the TEAEs across both arms were deemed AIT-related, the most frequent being injection-site swelling, pruritus, and erythema.

“Eighty percent of patients in [arm A] reached the first AIT injection of the maintenance phase without any dose adjustment,” noted the researchers. Moreover, among arm A participants who failed to reach the maintenance phase without dose adjustment, only three reported TEAEs that required a dose reduction.

Despite the higher incidence of systemic allergic reactions in arm A vs B (8.9 percent vs 2.4 percent), these were only classified as WAO^# grade 1/2 (ie, nonserious).

“[Moreover, most of] the systemic allergic reactions in [arm A] were observed in two patients from one trial site … [Therefore,] this result could be [due to] a specific trial site effect,” explained the researchers. This could be attributed to the injection-site hematoma described by one of the patients which, according to the researchers, could signal an incorrect administration technique that consequently led to the higher incidence of systemic allergic reactions.

“In summary, [our findings suggest that] a higher number of systemic allergic reactions does not necessarily indicate an accumulation due to the accelerated dose escalation scheme, but rather points to a specific trial site effect in combination with incorrect AIT handling,” they pointed out.

Of note was the different AE patterns observed with the timing of injections, as these mostly manifested following the first injection in arm A but only peaked after the fourth injection in arm B. The peak was observed at a dosage of about 1,000 TU, noted the researchers. “Hypothetically, these data might point towards faster tolerance induction in [arm A],” they said. Immunologic data would be essential to verify this theory as this could be a potential issue against the dose escalation scheme, they added.

One step up

“[AIT] is highly effective in patients with allergic rhinitis and allergic asthma and up to now, it is the only treatment that can modify the underlying course of allergic diseases … One hallmark of [AIT] is that increasing allergen doses are applied to reach the efficacious maintenance phase,” said the researchers. [Allergo J Int 2014;23:282-319; Allergy 2018;73:5-23]  However, the long-term updosing and maintenance phases may limit compliance and adherence, hence the goal to go “one step further”, they added. [J Allergy Clin Immunol 2013;132:353-360.e2]

Ultimately, the enhanced clinical and immunological tolerance could lead to improved compliance and adherence rates and fewer trips to the doctor, they said. Larger studies are warranted to substantiate the overall safety profile of the accelerated high-dose escalation strategy.