Rush-induction protocol enables safe aeroallergen immunotherapy
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Key takeaways:
- 12.6% of patients required epinephrine.
- Most reactions were mild with symptoms that may have been psychosomatic.
- Premedication may delay reactions during the protocol.
A four-step rush-induction protocol ending with 0.05 mL of the 1:10 v/v concentration was safe for patients at the beginning of aeroallergen therapy, according to a letter published in Annals of Allergy, Asthma & Immunology.
The protocol reduces time demands for patients with minimal risk, John C. Carlson, MD, PhD, specialist in allergy and clinical immunology, Ochsner Health System, New Orleans, and colleagues wrote.
“Allergy shots help to control allergy symptoms once a patient is on the full dose. Unfortunately, we have to work our way up to the full dose so that we don’t trigger an anaphylactic reaction,” Carlson told Healio.
A conventional weekly buildup schedule takes more than 7 months to get to the full therapeutic dose, Carlson explained, while the rush-induction protocol enables clinicians to cut this time to 2 to 3 months.
“Beyond getting relief much more quickly, it is really hard for patients to make it to clinic for the weekly injections for such a long stretch of time,” Carlson said. “Reducing the number of weekly visits makes it logistically possible for many people to get the injections while leading busy lives.”
Many patients are unable to take advantage of allergy shots because of the many weekly visits needed to reach the full dose, Carlson continued, which is the main reason why they come to his high-risk allergy center to get the rush-induction protocol.
“The rush protocols make it much more manageable, but we were worried about the risk,” Carlson said.
A review of all the authors’ high-risk protocols indicated that reactions were not caused by the number of allergens included in the allergy shots, but rather they were linked directly to the stopping dose.
“This was exciting because it means we can offer this safe protocol to anyone that wants to start on allergy shots,” Carlson said. “We hope that it makes this possible for busy people to get this treatment option.”
Study design, results
Patients were prescribed a single vial of extract completed with a half-day protocol with a final dose that was 10% of the antigenic content of the maintenance injection, or 0.5 mL at a 1:10 v/v concentration.
Due to concerns over increased risks for systemic allergic reactions, patients with two vials were stopped at 4% (0.2 mL, 1:10 v/v) of the maintenance dose for both vials. Similarly, patients with three or more vials were stopped at 1% (0.05 mL, 1:10 v/v) of the maintenance dose for each vial.
Patients also were prescribed premedication including prednisone, famotidine, second-generation antihistamine or montelukast beginning 2 days before the procedure, including a final dose of this premedication on the morning of the procedure.
Most patients completed their premedication, including 87% of the adult patients and 77% of the pediatric patients. Those who did not take all their premedication were allowed to proceed after engaging in joint decision-making.
With 103 patients overall (average age, 34 years; range, 7-67 years), the study included 52 patients with one vial (10% protocol); 31 with two vials (4% protocol); and 18 with three vials, one with four vials and one with five vials (all 1% protocol).
Every 15 to 30 minutes, patients received subcutaneous injections of increasing antigenic content, with starting doses of 0.3 mL of the 1:1,000 v/v vial and varied ending doses based on the protocol.
Twelve patients received epinephrine in the office, including 10 who received it after the last injections of their protocols. Another patient required it after the 2-hour observation. These patients included nine (17.3%) of those using the 10% protocol and four (12.9%) of those using the 4% protocol.
Additionally, nine of the 12 patients who received epinephrine in the clinic required a second dose after they had been discharged. The researchers presumed these reactions to be biphasic.
The researchers characterized most of the patients’ reactions as mild, although they also said that very high rates of symptoms or mild signs of reactions that could be systemic might have psychosomatic etiologies as well, with reassurance and distraction alleviating these symptoms.
Two patients using the 10% protocol developed grade 3 reactions based on the World Allergy Organization guidelines with symptoms before the procedure was complete. One of these patients did not complete the premedication regimen. The use of premedication may delay reactions during rush immunotherapy protocols, the researchers added.
Stopping the dose generated substantial differences in risks for reaction, the researchers continued, calling it likely that doses of a single allergen specific to individual patients cause reactions.
These risks may increase as the total number of allergens increases, the researchers added, because the probability that one allergen would exceed the reaction threshold for that patient would increase as well. Given the unexpectedly high rates of biphasic reactions, the researchers said, they advised caution when using the 10% dose.
Further, the researchers cautioned that although the extracts they used were prescribed according to guidelines, the quantities of allergenic proteins in individual extracts were not uniform across the study. Standardizing extract prescriptions should remove this variable in future prospective studies.
Similar to cluster protocols, the researchers said that stopping at the 1% dose may nearly eliminate risk for reactions requiring epinephrine as well.
Overall, the researchers concluded, using 0.3 mL of the 1:1,000 v/v vial, 0.1 mL of the 1:100 v/v vial, 0.3 mL of the 1:100 v/v vial and 0.05 mL of the 1:10 v/v vial injected 15 minutes apart can achieve savings in the buildup protocols most of the time.
Conclusions, next steps
The researchers had thought that reactions would be related to the number of allergens with which a person was being desensitized. Because of that fear, they stopped all patients with many allergies much earlier than patients with fewer allergies.
“Because we stopped so early, those highly allergic patients experienced no severe allergic reactions,” Carlson said.
“In contrast, patients that went further had many reactions, even if they were only being desensitized to a few allergens,” he continued. “We were surprised at how risky it was to go far in the protocol and how unexpectedly safe it was to stop earlier.”
Although rush-induction protocols enable patients to get to the therapeutic dose more quickly, it comes with an increased risk of an allergic reaction that requires epinephrine treatment, Carlson said.
“In our study, we determined the risk of an allergic reaction using different stopping points,” Carlson said. “Our safest stopping point got patients most of the way to the therapeutic dose with no allergic reactions. Going further caused more and more reactions.”
Although the researchers said they believe that the 1% protocol reduces time demands for patients who need immunotherapy with minimal risk to them, they also called for prospective and multisite trials to verify its safety.
The next big question is whether this approach can be used in the patients with the highest risk, which would be those with severe allergic asthma, Carlson said, adding that allergy shots change the immune system, which can lower the severity of asthma.
“Most centers will not give allergy shots to patients with severe asthma because there is a risk of death if things go wrong. But these are the patients that most benefit from allergy shots. The risk and reward are both high,” he said.
Carlson and his colleagues were able to provide this option to their patients because they work within a high-risk allergy center at Ochsner Hospital, Carlson said.
“If the protocol can be made safe for patients with severe asthma, this would enable allergists working outside of high-risk allergy clinics to help more patients,” he said.
In fact, Carlson said that he and his colleagues published their findings in the hopes that they would encourage other centers to offer this treatment to their patients.
“We’ve already been in contact with a few centers around the U.S. looking to implement it in their systems,” he said.
For more information:
John C. Carlson, MD, PhD, can be reached at john.carlson@ochsner.org.
Perspective
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The main advantage of this protocol is its quick time to achieve allergen desensitization. An additional major advantage is patient convenience, where patients receive several injections in 1 day without having to make repeated visits to the allergy clinic.
The disadvantage is the increased risk of a reaction. This is mitigated by providing steroids and antihistamines prior to the day of rush allergy shots.
The exact protocol was not outlined in this paper, but from the information provided, it seems like their protocol is very similar to the one we use in our clinic. However, we use the same protocol regardless of the number of vials administered. For the vast majority of our patients, they receive two vials. Also, the reported rate of reactions requiring epinephrine in this study was higher than what we experience.
Overall, it seems like the data the authors gathered reaffirmed current clinical practice. I do not see additional questions that need to be answered through further research.
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