Breaking Through Food Allergy Barriers with SLIT

Millions of people suffer from potentially life-threatening food allergies, living with fear and restriction in their daily lives. While oral immunotherapy (OIT) has shown promise in desensitizing patients to their allergenic foods, it carries some risks, especially for older children and adults. A team of scientists in Canada believe they may have found a safer way to move patients toward greater freedom through sublingual immunotherapy (SLIT).

Food allergies affect around 8% of children in the United States. The most common culprits are milk, eggs, peanuts, tree nuts, soy, wheat, fish and shellfish. An accidental exposure to even a tiny amount of the offending food can trigger a dangerous allergic reaction ranging from hives and swelling to breathing difficulties and loss of consciousness. Treatment is limited to strict avoidance and emergency injectable epinephrine in the event of an accidental reaction.

For many years, the only hope of gaining true tolerance to their allergens was through OIT—slowly increasing oral doses of the problematic food under medical supervision. However, over time it became clear that OIT posed certain risks, especially to older patients. Studies found that in comparison to children under 5, teenagers and adults were more likely to experience severe allergic reactions requiring epinephrine during OIT that could potentially be life-threatening.

Additionally, OIT regimens require frequent in-person clinic visits to slowly increase doses, often over a period of 6-12 months. This level of medical supervision poses challenges in terms of time, cost and accessibility for many patients and healthcare systems. With its looming risks and resource demands, OIT did not seem like a viable option for everyone with food allergies seeking relief. It was clear that safer alternatives were still needed.

Enter SLIT: While similar to OIT in using graded exposure to sensitize patients, SLIT involves holding drops or dissolving tablets of allergen extracts under the tongue rather than consuming them orally. The sublingual route provides a gentler means of exposure, bypassing the gastrointestinal system where allergic reactions are often most severe.

Early trials found SLIT to be much better tolerated than OIT, with far fewer systemic reactions. However, its effects trailed behind OIT in terms of how much allergen patients could eventually tolerate. Studies typically only raised SLIT doses to around 2-4 milligrams of allergen protein daily compared to 500-1000+ milligrams achievable with OIT. This meant SLIT alone still left patients at risk of potential allergic reactions from accidental exposures to their allergen in everyday life.

Seeking a better option, Dr. Lianne Soller and colleagues at BC Children’s Hospital in Vancouver designed a novel protocol combining SLIT with aspects of OIT. Their goal was to leverage SLIT’s impressive safety record while still moving patients closer to true desensitization.

They enrolled 188 patients ages 4-18 with multiple confirmed food allergies, three-quarters of whom had a history of moderate-severe past reactions. Over 3-5 supervised clinic visits every 4 weeks for build-up, patients steadily increased their SLIT doses under close monitoring. They then took their maintenance dose of 2 milligrams daily for 1-2 years.

After this initial SLIT phase, patients could attempt a “low dose oral food challenge” whereby they ingested increasing allergen amounts up to a cumulative 300 milligrams—roughly approximating the starting dose used in OIT maintenance. If they passed this low dose challenge without symptoms, they were instructed to continue taking 300 milligrams of the allergen orally each day as maintenance OIT therapy. If needed, those with mild reactions could escalate their OIT doses at home with guidance.

88% of patients managed to transition directly to OIT maintenance without requiring the typical multi-month clinic-based build-up phase

The results surprised even the scientists themselves. Out of 50 oral challenges attempted in 20 patients, 35 challenges—over two-thirds—were passed successfully without symptoms. An additional nine patients were able to transition to self-escalating OIT after mild reactions to their low dose challenges. In total, 88% of patients managed to transition directly to OIT maintenance without requiring the typical multi-month clinic-based build-up phase.

Equally important was the protocol’s tremendous safety record. Throughout 188 patients undergoing over 19,000 doses of SLIT build-up and maintenance, there was just one moderate allergic reaction requiring treatment and only four patients needed epinephrine injections—a rate of 2 reactions per 10,000 doses. No life-threatening grade 4 reactions occurred.

By comparison, previous studies found OIT carries a 5-10% risk of severe reactions requiring epinephrine, especially in older groups. Soller’s results suggest their SLIT pre-treatment drastically lowered this level of risk. The protocol also proved feasible to deliver within a real-world clinical setting at the busy children’s hospital.

“Our preliminary data show that an initial phase of SLIT to bypass supervised OIT buildups may not only be very safe but also effective for children where OIT is considered higher risk, such as teenagers,” says Soller. “It has the potential to improve access to immunotherapy through reduced health care needs.”

Of course, longer follow-up will be needed to confirm whether the protection from SLIT is durable over many years. Their next steps involve tracking how patients fare on extended OIT and whether they can one day eat thousands of milligrams of their allergens without fear, as is the ultimate goal of desensitization therapies.

Still, the initial proof-of-concept offered by this study immediately changes how scientists view SLIT’s potential as a gateway treatment to move patients along the path to tolerance. Their model could allow many who may have otherwise avoided OIT due to risks or barriers instead gain its benefits through a gentler introduction. Most importantly, it brings hope that through such collaborative innovation, the barriers surrounding food allergies can continue to bend, if not completely break, improving lives one patient at a time.

Reference(s)

1. DOI:https://doi.org/10.1016/j.jaip.2024.02.024

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