Sublingual immunotherapy may be used in buildup phase before oral immunotherapy
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Key takeaways:
- Children with histories of reactions, large SPT results or high serum-specific IgE were candidates.
- Buildup with sublingual immunotherapy lasted 1 to 2 years before an oral food challenge.
Children at high risk for reactions in oral immunotherapy for food allergy may benefit from sublingual immunotherapy before oral food challenges, according to a study published in the Journal of Allergy and Clinical Immunology: In Practice.
By eliminating the buildup visits of conventional OIT, this approach reduces both risks and health care utilization, Lianne Soller, PhD, allergy research manager, division of allergy, department of pediatrics, University of British Columbia, and colleagues wrote.
Generally, the researchers categorized OIT as safe and effective for infants and toddlers but risky for older children and adolescents. Also, the researchers wrote, these older patients face practical limitations that make long-term adherence difficult.
Although less effective, the researchers continued, sublingual immunotherapy (SLIT) may be safer for these older children and for children with greater risks, such as those with histories of severe reactions, high baseline serum-specific IgE (sIgE), or large baseline skin prick tests.
The researchers hypothesized that using SLIT for 1 to 2 years, followed by a low-dose OFC, would enable older patients and patients at higher risk for reaction to bypass supervised OIT buildup and begin OIT maintenance dosing.
Buildup phase
The study began with 188 pediatric patients (67.6% boys; median age, 11.3 years), with 61.7% who were allergic to multiple foods, who were enrolled in SLIT. Also, 75% of these patients were considered higher risk, with moderate to severe phenotypes.
These higher-risk patients included 23 with histories of grade 3 or 4 reactions before SLIT and SPT wheal diameters of 8 mm or less or sIgE of 50 kU/L or less; 90 with SPT wheal diameters greater than 8 mm, sIgE higher than 50 kU/L, and a history of mild reactions; and 28 with grade 3 or 4 reactions, SPT wheals greater than 8 mm and sIgE higher than 50 kU/L.
The cohort additionally included 146 (77.7%) patients who met International Food Allergy Consortium criterion 2, which includes a convincing objective history of a reaction with evidence of sensitization that is 95% or more of the positive predictive cutoffs for SPT or sIgE.
Two SLIT protocol options were available, beginning with 0.1 mg or 0.5 mg of protein, based on the severity of the patient’s allergy. Most patients followed a three-dose buildup protocol, although those with particularly severe features followed a five-dose buildup.
Every 4 weeks, a registered nurse conducted buildup visits with each patient, with 173 patients (92%) completing the buildup and 15 patients (8%) dropping out. The completion group and the dropout group had similar demographic and clinical variables as well as similar symptom profiles.
The most common reasons for dropping out included burdens, aversions and poor adherence with daily dosing (37.5%), lost to follow-up (31.25%) and recurrent reactions related to immunotherapy (25%).
Although 93.1% of the patients experienced symptoms during the buildup phase, 52.1% of them were grade 1, and 40.4% were grade 2. Only one patient (0.6%) had a grade 3 reaction, and none experienced any grade 4 reactions. Also, 82.7% of the grade 1 reactions were oral itch alone, which the researchers said was expected with SLIT.
The four patients (2.1%) who received epinephrine during buildup and went to the ED included one with a grade 1 reaction, two with a grade 2 reaction and one with a grade 3 reaction. Exercise was a cofactor contributing to anaphylaxis for one of these patients. All four patients continued SLIT without any further epinephrine.
Epinephrine rates during SLIT included 2.1 per 10,000 doses (0.02%), with 14.5 per 10,000 doses (0.15%) during buildup visits and 1.64 per 10,000 doses (0.16%) during doses at home.
The researchers also categorized the rate of grade 3 reactions as very low, including no grade 3 reactions during the buildup visits and 0.54 per 10,000 doses (0.005%) during the dosing at home.
Further, the researchers did not note any statistically significant differences in safety outcomes between the patients classified with moderate to severe phenotypes and those with mild phenotypes, nor were there any differences between patients with histories of moderate to severe reactions and those with mild histories but higher biomarkers.
Maintenance phase, OFCs
Target maintenance doses included 2 mg of food protein for patients aged 6 years and older and 4 mg of food protein for those aged younger than 6 years. Daily maintenance doses were administered for 1 to 2 years, with a median of 17.9 months (interquartile range, 12.8-21.5).
The researchers called the safety profile for the maintenance phase very favorable, with 41% experiencing grade 1 reactions and 3% experiencing grade 2 reactions. Also, none of the patients required epinephrine or an ED visit during the maintenance phase.
After the maintenance phase, 20 patients participated in 50 low-dose OFCs, with increasing amounts of food protein given every 20 to 30 minutes before reaching a cumulative dose of 330 mg or 340 mg of protein.
The researchers reported success in 35 OFCs (70%), and these patients began OIT with 300 mg maintenance doses. Also, nine patients who failed OFCs began taking OIT doses of 80 mg or higher and self-escalating to 300 mg at home, with as-needed medical guidance.
Overall, the researchers said, 44 of the OFCs (88%) enabled patients to transition to OIT without buildups that were medically supervised.
Five patients who experienced significant reactions during OFCs, including one who needed epinephrine and one who could not complete the OFC due to anxiety, were advised to continue SLIT for 1 to 2 more years before attempting the low-dose OFC again.
A few families decided to continue with SLIT instead of transitioning to OIT, the researchers said, but most wanted to expedite the switch because of its convenience compared with daily SLIT therapy.
Based on these findings, the researchers concluded that children with higher risks for reactions during OIT can use SLIT safely and effectively for the buildup phase of treatment before an OFC indicates they can continue with OIT for maintenance.
By bypassing OIT during the buildup phase, the researchers continued, patients are spared dozens of in-person visits with an allergist, reducing health care utilization, which is an advantage both for them and for publicly funded health care systems.
Perspective
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These findings are significant as a concept that can be further developed. People in this field have been thinking about various approaches as a potential “gateway drug” toward OIT. OIT is a robust therapy that can raise thresholds, potentially quite significantly, but carries frequent adverse events, especially for those most sensitive.
The concept is about using a therapy that may not be as robust as OIT but is very safe and might get that threshold high enough to more easily do OIT. Aiming this approach at those who might be predicted to have trouble with OIT is part of this concept.
Approaches could be epicutaneous immunotherapy (patch), omalizumab (Xolair; Genentech, Novartis), which is an anti-IgE approach, or, in this case, SLIT. These three have their own benefits and can meaningfully raise thresholds alone, but could also be viewed as a potential first step toward OIT.
The results here roughly align with past SLIT studies, meaning the approach was relatively safe (although there were reactions and the potential for significant ones is clear), and there can be decent increases in threshold. The study is interesting and unique in approaching multiple foods with SLIT, using commercial food products, and having a large number treated.
Admittedly, this is essentially a “real world” study that was not regimented, so there was no baseline OFC for most or no controls or comparison groups. It also was conducted at a single center. Therefore, generalizing results or contextualizing them is a problem to be solved with more studies, preferably controlled ones. The material is not standardized and the therapy not FDA approved, but the authors nicely discuss the practical issues in overcoming these barriers.
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