Allergen Immunotherapy
Allergen-specific therapies aim to modulate the allergic response to the specific allergens that someone is allergic to. The tricky part is that a lot of these therapies directly utilize the allergen in question, so there is a risk of an allergic reaction. A successful therapy maintains a high level of efficacy and safety.
Allergen-specific therapies allow an allergic individual to be exposed to a normal load of an allergen that they are allergic to without adverse effects. However, given the targeted nature of this treatment, if someone is allergic to multiple allergens, such as someone allergic to multiple foods, the therapy often fails to relieve someone of all of their allergies within a reasonable time frame at a reasonable cost.
Allergen Immunotherapy (AIT)(1, 2, 3, 7)
AIT is the process of administering incrementally increasing doses of a target allergen, typically over years of time, with the goal of inducing tolerance. It is unknown if the clinical tolerance induced by AIT is equivalent to "true" tolerance, the permanent state of non-reactivity experienced by nonallergic individuals, so the terms desensitization and sustained unresponsiveness (tolerance) are used when referring to the efficacy of AIT. Desensitization is a temporary state of hyporesponsiveness that is maintained by frequent exposure to the allergen, while tolerance is a prolonged state of hyporesponsiveness which persists after therapy.
AIT traditionally follows a pattern of a build-up phase and a maintenance phase. Treatment starts in the build-up phase where at first a very small dose of an allergen is administered, but over time the dose is increased with the goal of reaching an optimal dose. This optimal dose is different for each allergen and attempts to maximize efficacy and safety. Once this optimal dose is reached, the maintenance phase begins.
The goal of the maintenance phase is to continue to expose an individual to the allergen, but at a less frequent rate than the build-up phase. The maintenance dose can be the same as the optimal dose, or it may be less if efficacy has been demonstrated. If an individual were to stop taking their maintenance dose they may have sustained unresponsiveness for some time, but the desensitization gained from AIT is likely to wear off.
The primary mechanism leading to tolerance is an alteration of the Th2 immune profile. This is associated with an increase of T regulatory cells (Treg) and the Th1 immune response, which suppresses Th2 immunity via cytokines and IgG and IgG4 antibodies which compete with IgE.
In the aim to find the best route of exposure to induce tolerance, many different forms of AIT are currently being trialed.
Forms of AIT:
- Oral Immunotherapy (OIT)
- Sublingual Immunotherapy (SLIT)
- Subcutaneous Immunotherapy (SCIT) - "Allergy Shots"
- Epicutaneous Immunotherapy (EPIT)
- Intralymphatic Immunotherapy (ILIT)
- Intradermal Immunotherapy (IDIT)
- Tolerance Induction Program™ (TIP™)
Depending on many different factors, such as the specific allergen or the age of the individual, we are finding that different forms of AIT are working better than others. For example, SCIT has been successful for pollen and insect venom allergens, but it is avoided in favor of OIT for food allergens. Additionally, different forms of AIT have been shown to be less effective for individuals 18 years of age or older, while others have proven to be efficacious for the elderly.5
Oral Immunotherapy (OIT)1
In OIT, an allergen is ingested in gradually increasing amounts until a maintenance dose is reached. The goal of oral immunotherapy is to leverage the biology of the gastrointestinal system to induce desensitization or tolerance.
The first dose is monitored in the clinic, but subsequent doses can generally be self-administered at home once daily.
Currently, only one OIT treatment is FDA-Approved for peanut allergy (PALFORZIA).6
PALFORZIA is a powder that is manufactured from peanuts and packaged in pull-apart color-coded capsules for Dose Escalation and Up-Dosing. Unfortunately, there are many limitations to this treatment; it only induces desensitization (not tolerance), is not effective for people 18 years of age or older, most people experience adverse events, and the end result is the reduction of allergic reaction severity for accidental exposure, meaning that the patient still can’t include peanuts in their diet.
Sublingual Immunotherapy (SLIT)(1, 8)
In SLIT, liquid allergen extract is applied under the tongue through drops or a dissolvable tablet. The goal of sublingual immunotherapy is to leverage the biology of the mouth to induce desensitization or tolerance. Since the allergens are directly absorbed in the mouth, SLIT circumvents the rest of the gastrointestinal system, meaning that treatment is still effective in patients with gut disorders.
The first dose is monitored in the clinic, but subsequent doses can generally be self-administered at home once daily.
Here are some FDA-approved SLIT treatments that are available:
Grastek (Timothy grass)
Odactra (Dust mite)
Oralair (Grass pollens)
Ragwitex (Ragweed pollen)
There are also custom-made SLIT treatments offered by hospitals and clinics that expand the allergens offered.
Subcutaneous Immunotherapy (SCIT)1
In SCIT, also known as “allergy shots”, an allergen is administered by subcutaneous injection in incrementally increasing doses to induce desensitization or tolerance.
Due to the injection process and risks associated with administering SCIT, it cannot be self-administered and must be administered by a medical professional.
Typically, subcutaneous immunotherapy is only performed for various environmental allergens such as pollens, pet allergens, and insect sting venoms due to the high incidence of adverse effects with food allergens.
Intradermal Immunotherapy (IDIT)4
In IDIT, allergens are injected intradermally and can drain into lymph nodes to induce desensitization or tolerance.
Due to the injection process and risks associated with administering ILIT, it cannot be self-administered and must be administered by a medical professional.
Currently, no IDIT treatments are FDA-approved as this form of AIT is still severely underdeveloped.
Intralymphatic Immunotherapy (ILIT)4
© 2017 Kim ST, Park SH, Lee SM, Lee SP 10
In ILIT, allergens are directly injected into inguinal lymph nodes using ultrasound guidance. The goal of intralymphatic immunotherapy is to leverage the biology of the lymph nodes to induce desensitization or tolerance.
Due to the injection process and risks associated with administering ILIT, it cannot be self-administered and must be administered by a medical professional.
Currently, no ILIT treatments are FDA-approved as this form of AIT is still severely underdeveloped.
Epicutaneous Immunotherapy (EPIT)(1, 2, 4)
In EPIT, food protein is electrosprayed onto a patch that is applied to intact skin on the upper arm or between the shoulders. The goal of epicutaneous immunotherapy is to leverage the biology of the skin barrier to induce desensitization or tolerance.
The first patch is monitored in the clinic, but subsequent patches can generally be self-administered at home once daily.
Currently, no EPIT treatments are FDA-approved, but products such as Viaskin™ Peanut are trying to change that.
Tolerance Induction Program™ (TIP™)
TIP™ is a food allergy treatment program run by the Southern California Food Allergy Institute™. It relies on the concept of precision medicine, where it takes in various data points and comes up with a personalized treatment plan. Essentially, TIP™ is AIT + data + analytics.
In my opinion, TIP™ is the best option available for consumers today to treat food allergies.
The problem? It is only in California, it is quite expensive, and there is a long waitlist. TIP™ is not FDA-Approved and has not been through clinical trials because modern-day clinical trials rely on the concept of a single treatment being applied equally to many patients. A precision medicine approach is a personalized treatment being applied to one patient.
I am someone that believes data + AI will eventually solve all of humanity's health problems, so I would like to see the antiquated healthcare system make changes to better allow precision medicine solutions to be expanded across the world.