Peanut sublingual immunotherapy reaches clinically significant desensitization in children

March 31, 2023

4 min read

Source/Disclosures

Disclosures:
Kim reports serving on the scientific advisory board for ALK-Abelló, DBV Technologies, Kenota Health and Ukko Inc.; being a consultant for Allergenis, Allergy Therapeutics Ltd., Belhaven Pharma, Duke Clinical Research Institute, Genentech and Nutricia; and receiving grant support from the NIH National Institute of Allergy and Infectious Diseases and Food Allergy Research and Education. Please see the study for all other authors’ relevant financial disclosures.

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Key takeaways:

• The mean successfully completed dose increased from 48 mg to 2,723 mg of peanut protein by 48 months.
• 70% achieved clinically significant desensitization, and 36% achieved full desensitization.

Sublingual immunotherapy induced clinically significant desensitization with a favorable safety profile among children with peanut allergy, according to a study published in The Journal of Allergy and Clinical Immunology.

Along with its ease of administration, these factors make the treatment a promising option for peanut allergy, Edwin H. Kim, MD, MS, associate professor of pediatrics and division chief of UNC Pediatric Allergy & Immunology at University of North Carolina School of Medicine, and colleagues wrote.

Considering its ease of administration, safety and tolerability, researchers called sublingual immunotherapy a promising option for treating peanut allergy. Image: Adobe Stock

The study enrolled 54 participants (39 boys; 49 white) aged 2.3 to 11.9 years (mean age, 7.1 ± 2.6 years) with a confirmed peanut allergy, including 15 who had additional food allergies.

Edwin H. Kim

The researchers assessed reaction thresholds via double-blind placebo-controlled food challenges (DBPCFCs) at baseline, after 48 months of peanut sublingual immunotherapy (SLIT) and after 1 to 17 weeks of avoidance, in addition to other periodic testing.

However, only 47 participants completed peanut SLIT dosing and the 48-month DBPCFC, considered the per-protocol (PP) population. Further, 37 completed the avoidance DBPCFC.

The successfully consumed dose (SCD) increased from a baseline mean of 48.4 ± 93.2 mg to 2,723 ± 1904 mg of peanut protein by 48 months among the PP population. Also, 17 of these participants achieved an SCD of 5,000 mg without any symptoms, and 33 achieved an SCD of 800 mg or more, which the researchers considered clinically significant desensitization.

Mean wheal sizes in peanut skin prick tests decreased from 16.5 ± 7 mm at baseline to 9.1 ± 4.9 mm after 48 months in the PP group (P < .0001), with significant decreases after just 12 months, the researchers said.

The researchers also said they observed significant increases in peanut-specific IgE (Pn-sIgE) from baseline through 6 months with a return toward baseline by 12 months, and significant decreases by 24 months and through 48 months. Specific figures included a mean of 213 ± 351.2 kUA/L at baseline to 60.7 ± 162.7 kUA/L after 48 months (P < .0001).

Additionally, the researchers noted an increase in peanut-specific IgG4 (Pn-sIgG4) from a mean of 0.8 ± 1.4 mg/L at baseline to 20.6 ± 47.9 mg/L at 48 months, with significant increases observed after 6 months (P < .0001).

The ratio between Pn-sIgG4 and Pn-sIgE increased from baseline to 6 months and then reached statistical significance at 12 months, the researchers continued, with an overall increase from a mean of 6.7 ± 10.7 mg/L at baseline to 1,176 ± 2,823 mg/L at 48 months (P = .0012).

Decreases in the mean percentage of CD63+ basophils at 10 ng/mL and 1 ng/mL dilutions were seen at 6 months and persisted through treatment. For example, the mean percentage fell from 34% ± 30.1% at baseline to 18.8% ± 22.9% after 48 months at the 10 ng/mL dilution (P = .0012). Similarly, they fell from 19.7% ± 24.8% at baseline to 9.1% ± 17.8% at 48 months at the 1 ng/mL dilution (P = .0178).

Decreases in mean cytokine levels from baseline to 48 months included 2.2 ± 3.2 pg/mL to 0.6 ± 0.6 pg/mL for IL-4 (P = .0012), 778.3 ± 949.6 pg/mL to 141.1 ± 144.6 pg/mL for IL-5 (P = .0002) and 40.9 ± 46.9 pg/mL to 9.6 ± 11.4 pg/mL for IL-13 (P < .0001).

Interferon-gamma levels only decreased significantly after 48 months, but tumor necrosis factor-alpha levels remained the same after peanut SLIT. IL-10 levels fell from baseline to 12 months and then through 48 months as well.

Among the 37 participants who completed the avoidance phase, the median time to loss of clinically significant desensitization was 22 weeks (interquartile range [IQR], 10-100 weeks).

When the researchers used 300 mg as an alternative threshold for clinically significant desensitization, none of the participants in the avoidance phase experienced any reactions below this total.

The researchers also defined loss of desensitization as losing a step in the DBPCFC threshold and found that 49% of the avoidance group lost desensitization within the 17-week follow-up time.

With interval-censored survival analysis, the researchers continued, they calculated a 12-week median time to loss of one step during the DBPCFC (IQR, 11-12 weeks).

With 81,031 possible dosing days, the researchers reported that the participants took 97.6% of their peanut SLIT doses. Symptoms followed 4% of home-administered doses, with a 0.49% median rate of reaction per participant per dose.

Seven participants reported 2,525 of the 3,203 (83.3%) of the dosing symptoms, and one of these participants withdrew from the study. Oropharyngeal itching and lip swelling occurred with 3.7% of doses. Skin symptoms and abdominal symptoms happened with 0.1% of doses each.

Epinephrine was not used to treat any of the SLIT dosing symptoms, but antihistamines were administered for 143 symptom episodes, or 0.14% of the doses taken.

Based on the baseline biomarkers, the researchers hypothesized that the participants were not likely to outgrow their peanut allergy. Yet the changes in these biomarkers indicated that peanut SLIT broadly alters the allergic response across mast cells, basophils, B cells and T cells, with the possibility of a more durable desensitization effect.

Also, the researchers said their findings indicate that patients on SLIT can withstand accidental ingestions of peanut even with lapses in therapy lasting up to several weeks. Together, they concluded, SLIT is a promising option for treating peanut allergy.

Perspective

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Jennifer A. Dantzer, MD, MHS

To date, multiple modalities of immunotherapy for peanut food allergy have been investigated, including oral, SLIT, epicutaneous and subcutaneous immunotherapy. There is currently one FDA-approved product for peanut OIT.

While OIT may be efficacious, there is also a risk for potentially severe adverse side effects, as well as the need for frequent office visits. Therefore, it is important to continue to pursue alternative options. One such option is SLIT.

This single-site, open-label study adds some insight into the potential safety and efficacy of peanut SLIT for the treatment of peanut allergy in children aged 1 to 11 years. It is significant that the study showed a mean successfully consumed dose of 2,723 mg of peanut protein (approximately nine peanuts), with 70% of participants tolerating at least 800 mg (approximately 2.5 peanuts).

Importantly, as shown in other studies, not all participants had the same improvement. Another important finding was that SLIT doses overall seemed to be well tolerated, with most dosing symptoms being oropharyngeal and no epinephrine administered for SLIT dosing symptoms.

This study also implemented a unique method to assess durability of desensitization during the avoidance period. In most trials that include an avoidance period, all participants avoid the allergen for the same length of time, and then typically food challenges are repeated. However, Kim et al randomly assigned participants to 1 to 17 weeks of peanut SLIT avoidance before the final DBPCFC. They then used this information to assess time to desensitization. They estimated the median time to loss of desensitization was 22 weeks, which is longer than seen in many prior immunotherapy studies.

This was, as the authors noted, a “first-of-its-kind” approach, and there is a great need for additional information about duration of desensitization if one returns to avoidance. It is important to remember that there can be great variability between individuals in time required for loss of desensitization and, hence, why it would be great to see these methods replicated in future studies.

The main take-home is that SLIT might be a promising option as a relatively safe and effective therapy for some children with peanut allergy. Ultimately, additional large, multicenter, randomized, placebo-controlled studies in diverse patient populations would be needed to obtain generalizable information that could be used to change clinical care.

Jennifer A. Dantzer, MD, MHS

Assistant Professor of Pediatrics, Pediatric Allergy, Immunology and Rheumatology, Johns Hopkins School of Medicine

Healio Allergy/Asthma Peer Perspective Board Member

Disclosures: Dantzer reports no relevant financial disclosures.

Perspective

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Jay Lieberman, MD

This is a very nice, open-label study.

The results are significant. They show that most patients were desensitized, which we already knew SLIT could do. More importantly, they show that many patients remained desensitized even after avoiding the therapy for several weeks. This appears to be most evident in the kids who were able to tolerate the most amount of peanut during the 48-month oral food challenge. This is clinically relevant and pretty much new information for long-term SLIT.

I do not do food allergy SLIT. Very few allergists in the country do, outside of research like this. So, I cannot compare it with my own experience. But my hope is that one day, we will have a uniform and standardized SLIT to offer our food allergy patients.

The next step will be deciding how this would fit into regular practice. Are allergists going to take this into the real world? Will this be commercialized and have a standardized, regulated product? What about other foods? This should work the same for other foods. Can you do multi-food SLIT? Would this change safety or efficacy?

Overall, this showed what we know of SLIT. It is safer than OIT, and it can work for many patients as a desensitizing option.

However, this study also showed some more real-world and longer-term data that is very helpful. It was a little surprising how well some patients did off therapy for several weeks. I did not expect this, to be honest. I am very hopeful with these data, although I have no scientific rationale to suspect SLIT is a “cure” for food allergy, much in the same way we do not tell patients OIT is a “cure” for food allergy.

Also, it obviously was not controlled, although some of those studies have been, which has to be recognized.

And, as the authors point out, the patients were asked not to intake or expose themselves to any peanut during the avoidance phase of the trial. One never really knows if families really do this. They just went through 4 years of therapy. They showed that their child responded to the therapy. Then we tell them, “OK, now just stop the therapy in the name of science, and do not allow your child any peanut to prove how long this therapy works after you stop it.” It takes a lot of faith to assume no parents continue some form of therapy in these studies. But maybe I am just a skeptic.

Jay Lieberman, MD

Associate Professor and Director of the Allergy and Immunology Training Program, University of Tennessee Health Science Center, Le Bonheur Children’s Hospital

Disclosures: Lieberman reports having investigator roles with Aimmune Therapeutics, DBV, Novartis and Regeneron; having data safety monitoring board roles with AbbVie and Siolta; having advisory board roles with ALK, Aquestive Therapeutics, DBV and Novartis; and serving as an associate editor for Annals of Allergy, Asthma & Immunology and as an executive board member for the American Board of Allergy and Immunology.

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