Venom immunotherapy achieves maintenance doses after three up-dosing sessions

Key takeaways:

• Up-dosing sessions occurred weekly, followed by monthly maintenance dosing.
• Venoms included honeybee, yellow jacket, wasp, white faced hornet and yellow hornet.
• Reactions during treatment were grade 1 or 2.

A three-session rush venom immunotherapy protocol was safe and effective with nearly all patients achieving maintenance dosing with few systemic reactions, according to a study published in Annals of Allergy, Asthma & Immunology.

This cost-effective approach also may be more attractive to patients who need rapid and safe protection for venom allergies, Megan E. McCarty, MD, allergy-immunology fellow, division of pulmonary, allergy, critical care medicine and sleep medicine, University of Pittsburgh Medical Center, and colleagues wrote.

The rush protocol

Conventional venom immunotherapy requires gradual buildup with standardized venom extract over 3.5 to 4 months of weekly doses before monthly maintenance dosing.

The researchers’ rush protocol used three weekly buildup doses before monthly maintenance dosing.

The day before and on the day of the first and second sessions, patients using this protocol received premedication with 40 mg of prednisone, 10 mg of montelukast and full doses of second-generation H1 and H2 antihistamines. On the day of the third session, patients received a full dose of second-generation H1 antihistamine before treatment.

Venoms included honeybee, yellow jacket, wasp, white faced hornet and yellow hornet. Patients received extracts for each venom to which they were sensitized.

The first session involved five hourly doses of extracts, including 0.1 µg, 1 µg, 10 µg, and two doses of 20 µg, for a cumulative dose of 51.1 µg. The second session included three hourly doses, including two doses of 20 µg and one of 30 µg, for a 70 µg total. The third session included two hourly doses of 50 µg for a 100 µg total.

During each session, patients were observed for an hour following their final dose.

Monthly maintenance dosing with 100 µg of extracts of each venom that patients were allergic to followed 4 weeks after the third session. Thirty-minute observational periods followed each maintenance dose.

Patient population

The cohort included 55 adults (median age, 47 years; interquartile range [IQR], 37-57; 28% women) with at least one venom allergy. Each patient also had a history of systemic reactions to stinging insects, with 24 (44%) reporting two or more systemic reactions.

The researchers classified 17 of these reactions (31%) as severe, 28 (51%) as moderate and 10 (18%) as mild based on Brown grading criteria.

Reactions primarily involved cutaneous-mucosal tissue (n = 47; 85%), including 33 cases of swelling, 24 cases of urticaria, 10 cases of pruritus and three cases of flushing. Most patients (n = 31; 56%) also experienced respiratory symptoms, including the lower airway in 26 cases and upper airway or throat swelling in 13 cases. Cardiovascular (n = 21; 38%) and gastrointestinal (n = 8; 15%) symptoms were reported as well.

Yellow jacket was the most common allergy (n = 52; 95%). White hornet was next (n = 48; 87%), followed by yellow hornet (n = 42; 76%), wasp (n = 39; 71%) and honeybee (n = 37; 67%). Most patients reported more than one sensitization, and only six patients received venom immunotherapy for just one venom.

Treatment results

Forty-six (84%) of the patients did not experience any systemic reactions during the three up-dosing sessions. Five patients only had systemic reactions during the first session, one only reacted during the second session, two only had reactions during the third session, and one reacted during all three sessions.

Four of the nine patients who had systemic reactions (44%) and eight of the 46 patients who did not have systemic reactions (17%) had asthma.

Also, all the patients with systemic reactions were sensitized to yellow jacket and white hornet. Eight were sensitized to wasp, seven were sensitized to hornet and six were sensitized to honeybee.

All the reactions during the three up-dosing sessions were grade 1 or 2 according to the Brown criteria, and cutaneous reactions were most common.

During the maintenance period, five patients (8%) had six systemic reactions, including one classified as grade 1, two classified as grade 2 and three classified as grade 4. Three of these patients also had reactions during the three up-dosing sessions.

Furthermore, 11 of the patients who had a systemic reaction during any phase of treatment (18%) were on an angiotensin-converting enzyme inhibitor, compared with none of the patients who did not have any systemic reactions (P = .004).

Nearly all the patients, 53 of 55 (96%), achieved full maintenance dosing of 100 µg. The other two patients used 50 µg maintenance doses because they had adverse reactions including joint aches, chest tightness and shortness of breath with the full dose.

The researchers also collected baseline tryptase levels from 44 patients (80%), with a median of 5.1 ng/mL (IQR, 4-6.9). Levels equaled or exceeded 8 ng/mL for eight patients and equaled or exceeded 11.4 ng/mL for three patients.

Baseline tryptase level and severity of initial sting reaction according to Brown grading criteria were not associated, the researchers said.

Seven of the nine patients with systemic reactions during the three up-dosing sessions also had baseline tryptase levels recorded. Six of them had levels less than 5 ng/mL, and the seventh patient had a level of 13.5 ng/mL.

Nine of the 11 patients with systemic reactions anytime during treatment had baseline tryptase levels recorded as well. Seven had levels less than 5 ng/mL. Also, one had a level of 8.2 ng/mL, and another had a level of 13.5 ng/mL, both of which the researchers called elevated.

Thirty-four patients in the cohort (62%) continued receiving maintenance or build-up doses over a median of 38 months, including 10 patients who completed 5 years or more and six patients continuing treatment beyond 5 years.

Among the 45 patients who completed less than 5 years of treatment, 24 were still receiving treatment and 21 had discontinued treatment due to adverse effects, comorbidities, the COVID-19 pandemic, financial or insurance issues, or loss of follow-up, with one patient discontinuing maintenance treatment because of a systemic reaction.

Also, 91% of the patients with treatment adherence and 67% of those who discontinued treatment prematurely had a moderate to severe reaction to their index sting based on Brown criteria (P = .024).

Ten patients (18%) were stung again while they were on 100 µg of maintenance treatment. Three experienced local swelling, one had mild shortness of breath treated with antihistamine and one preventatively used an epinephrine autoinjector. The other five patients did not have any reactions.

Conclusions, next steps

Based on these results, the researchers called their rush venom immunotherapy protocol a safe and effective means for reaching maintenance dosing with results comparable to other rush protocols.

Also, the researchers noted that their protocol does not require inpatient hospitalization and that it includes all Hymenoptera venoms, with fewer injections and visits as well as noninvasive monitoring.

With 55 of 58 patients choosing this protocol over traditional build-up approaches through shared decision-making, the researchers further said that it is a more cost effective and attractive option for physicians and patients alike.