Sublingual immunotherapy, a new treatment for peanut, could offer patients a safe and effective way to protect themselves from severe allergic reactions or even anaphylaxis, found a study partly funded by the National Institutes of Health.
People allergic to peanuts may have a new way to protect themselves from severe allergic reactions to accidental peanut exposure. It’s called sublingual immunotherapy – or SLIT – and it involves putting a minuscule amount of liquefied peanut protein under the tongue, where it is absorbed immediately into the blood stream to desensitize the immune system to larger amounts of peanut protein.
The research shows that SLIT could offer patients a safe and effective way to protect themselves from severe allergic reactions or even anaphylaxis. Dr Quefeng Li, assistant professor in the department of biostatistics at the University of North Carolina Gillings School of Global Public Health, was a study co-author.
“As a parent of two children with nut allergies, I know the fear parents face and the need for better treatments,” said first author Dr Edwin Kim, assistant professor of medicine at the UNC School of Medicine. “We now have the first long-term data showing that sublingual immunotherapy is safe and tolerable, while offering a strong amount of protection.”
Clinician scientists have developed three main immunotherapeutic ways to treat nut allergies, and all of them attempt to desensitise the immune system to nut proteins to help patients avoid severe allergic reactions. According to Kim, about 100 mg of peanut protein can trigger a severe allergic reaction. That’s the sort of trace amount people fear can show up in food “manufactured in a facility that processes peanuts.” For reference, one peanut kernel contains about 300 mg.
“The main idea behind immunotherapy is not for kids to be able to eat peanut butter and jelly sandwiches,” Kim said. “It’s to keep them safe from the small hidden exposures that could occur with packaged foods, at restaurants and with other food exposures.”
One immunotherapy method involves a patch on the skin that releases a small amount of peanut protein through the skin to desensitise the immune system. This approach has proved safe in clinical research but perhaps not as effective as researchers had hoped. It could become an US Food and Drug Administration (FDA)-approved treatment.
A second approach is called oral immunotherapy (OIT), which currently is under FDA review with a decision expected this year. OIT requires patients to ingest a small portion of peanut protein daily; over the course of time, this can desensitise the immune system to accidental exposures. In a large phase 3 OIT clinical trial, patients initially ingested 0.5 mg of peanut and increased the amount to 300 mg over the course of many weeks and then maintained that 300 mg daily intake for the remainder of the year. This trial showed substantial effectiveness in protecting patients, but some patients suffered serious side effects. A subsequent meta-analysis of OIT clinical trial data suggested that more clinical research on OIT was needed due to the risk of serious side effects.
A third approach is SLIT. Instead of having patients ingest peanut protein, doctors place a small amount of peanut protein under patients’ tongues, where it is immediately absorbed. Because the peanut protein avoids digestion, patients are given much less peanut protein – about 0.0002 mg initially. This amount then increases over the course of months to just 2 mg.
In 2011, Kim and colleagues conducted a small study of 18 patients to show that SLIT was safe and effective over the course of one year. Since then, Kim and his research team have followed 48 patients in the SLIT protocol of 2 mg daily for five years. In the new paper, the researchers showed that 67% of these patients were able to tolerate at least 750 mg of peanut protein without serious side effects. About 25% could tolerate 5,000 mg.
These data show that SLIT was about as effective as OIT, though the SLIT study was much smaller. SLIT also posed a much lower risk of serious side effects. The most common side effect was itchiness around the mouth that lasted about 15 minutes and did not need treatment. No one left the multi-year study because of side effects.
“SLIT participants tolerated between 10 and 20 times more peanut protein than it would take for someone to get sick,” Kim said. “We think this provides a good cushion of protection – maybe not quite as good as OIT – but with an easier mechanism (sublingually) and, as far as we can tell right now, a better safety signal.”
Kim and colleagues also are studying SLIT in a subset of children ages one to four because separate OIT data indicated that younger patients have a stronger, more lasting benefit to immunotherapy.
“We focus on the idea there is no one perfect drug for food allergy,” Kim said. “There will have to be a lot of shared decisions between physicians, patients and parents about what method of treatment is best for each patient. We think SLIT could be a good option for a subset of patients.”
The National Institutes of Health, the Wallace Foundation and Food Allergy Research & Education funded this research.
Background: Peanut sublingual immunotherapy (SLIT) for 1 year has been shown to induce modest clinical desensitization in allergic children. Studies of oral immunotherapy, epicutaneous immunotherapy, and SLIT have suggested additional benefit with extended treatment.
Objective: We sought to investigate the safety, clinical effectiveness, and immunologic changes with long-term SLIT in children with peanut allergy.
Methods: Children with peanut allergy aged 1 to 11 years underwent extended maintenance SLIT with 2 mg/d peanut protein for up to 5 years. Subjects with peanut skin test wheals of less than 5 mm and peanut-specific IgE levels of less than 15 kU/L were allowed to discontinue therapy early. Desensitization was assessed through a double-blind, placebo-controlled food challenge (DBPCFC) with up to 5000 mg of peanut protein after completion of SLIT dosing. Sustained unresponsiveness was further assessed by using identical DBPCFCs after 2 to 4 weeks without peanut exposure.
Results: Thirty-seven of 48 subjects completed 3 to 5 years of peanut SLIT, with 67% (32/48) successfully consuming 750 mg or more during DBPCFCs. Furthermore, 25% (12/48) passed the 5000-mg DBPCFC without clinical symptoms, with 10 of these 12 demonstrating sustained unresponsiveness after 2 to 4 weeks. Side effects were reported with 4.8% of doses, with transient oropharyngeal itching reported most commonly. Side effects requiring antihistamine treatment were uncommon (0.21%), and no epinephrine was administered. Peanut skin test wheals, peanut-specific IgE levels, and basophil activation decreased significantly, and peanut-specific IgG4 levels increased significantly after peanut SLIT.
Conclusion: Extended-therapy peanut SLIT provided clinically meaningful desensitization in the majority of children with peanut allergy that was balanced with ease of administration and a favorable safety profile.
Edwin H Kim, Luanna Yang, Ping Ye, Rishu Guo, Quefeng Li, Michael D Kulis, A Wesley Burks