The Pollen Pill: Sublingual Pollen Immunotherapy

Illustrated by Shanthi Deivanayagam

The arrival of spring traditionally evokes feelings of renewal and hope as the cold of winter recedes and green plant life returns to the landscape. However, for up to 60 million people in the United States (including myself), spring is also accompanied by a runny nose, itchy eyes, asthma, and/or the addition of antihistamines to the shopping list [16]. Caused by an immune reaction to pollen from trees in spring and grass in early summer and fall, pollen allergies are relatively common in America and have even been on the rise [14].  

Beyond being a nuisance to allergy sufferers, pollen allergies can affect productivity and one’s academic performance. Studies have shown that during pollen season, having pollen allergies reduces sleep quality, increases fatigue, reduces social interactions, increases distraction and even correlates with lower standardized test scores [10, 3]. It is clear that untreated allergies can significantly impact one’s quality of life and even their higher education opportunities. For the effects that pollen allergies have on individuals and particularly students, there are few treatments available. The current way that individuals can manage symptoms is by taking antihistamines. Unfortunately, it is meant to only moderate symptoms and cannot prevent pollen allergies long-term.  

For those with severe symptoms, subcutaneous immunotherapy (SCIT) is a potential solution. Commonly referred to as “allergy shots,” SCIT desensitizes the immune system to pollen by repeatedly introducing pollen into the body. This results in greater tolerance for the allergen through increased Regulation T cell (Reg T) prevalence and lower IgE production (antibody associated with allergic reactions) [13]. Studies looking at the efficacy of SCIT and found that after six to nine years following treatment, most subjects using SCIT had reduced allergy symptoms and became less reliant on antihistamines compared to those who did not [8]. Thus, studies show that SCIT can potentially provide a long-term solution or cure to pollen allergies that antihistamines cannot.  

Despite its benefits, SCIT must be administered by clinicians. Unfortunately, although rare, SCIT can cause severe allergic reactions if not properly used. This means that SCIT can be inconvenient and uncomfortable for patients as it requires individuals to travel to a clinic or hospital to receive shots for up to five years, sometimes as frequently as three times a week in the beginning [7, 5, 2]. The high time investment and dedication required to complete treatment could reduce the number of individuals willing to receive SCIT, barring individuals from long-term allergy relief.  

However, a relatively new treatment known as sublingual immunotherapy (SLIT) may provide a more convenient way to administer immunotherapy. Reminiscent of the advice for allergy sufferers to consume local honey, the allergen is simply packed into a pill or drop (or even as an inhalant) and placed under the tongue before being consumed. It is hypothesized that the oral mucosa can absorb allergens, allowing the immune system to come in contact with and become tolerant towards the allergen [1].  Regardless of the mechanism, the primary benefit of SLIT over SCIT is the much lower risk of severe reactions to the treatment, making it safe for patients to self-administer pills at home without the need of constant trips to the clinic or hospital to receive doses [2]. Given this convenience, one would assume that compliance would be higher for SLIT compared to SCIT.  

Surprisingly, studies have found the exact opposite. A study of German pediatric patients by Christian Vogelberg et al found that the dropout rate for SLIT versus SCIT was 54% and 47% respectively [17]. Another study of Italian adults found the rate to be 46% and 26.7% respectively [9]. How could a treatment that is administered at home have lower patient adherence than one that requires regular visits to a clinic? Multiple studies including the German study points out that SLIT is generally less effective than SCIT at treating allergies (and particularly for tree pollen allergies when compared to grass pollen allergies) [17, 15]. One could imagine that if a patient was not seeing the results they wanted from the treatment, they would be more likely to give up on it. Of course, SLIT’s lack of efficacy is likely exacerbated by the low compliance in the first place. Additionally, newer research shows existing SLIT dosages are too low to be properly effective in patients [12]. Therefore, increasing the dosage could resolve this discrepancy, increasing compliance and further increasing the efficacy of SLIT to match that of SCIT.  

Furthermore, some have pointed out that SLIT may be too expensive and not worth the cost. Many of these studies were conducted in Europe where the cost of SLIT is greater than SCIT, further de-incentivizing individuals from continuing with SLIT as opposed to SCIT [4]. Similarly, a study comparing SCIT and SLIT in Canada also found that SLIT was more expensive, rendering it more difficult for patients to afford SLIT over SCIT. However, the authors note that after factoring in indirect costs such as transportation, SLIT became the cheaper option [6]. In addition to the added inconvenience of SCIT, traveling to and from a clinic or hospital to receive SCIT likely leads to increased costs. Thus, taking SLIT may be more economically viable only after factoring in the indirect costs.  

In terms of both economic viability and efficacy, SLIT appears to have potential as a useful and feasible alternative to SCIT. Many questions persist with regards to the correct schedule, dosage, and the efficacy of SLIT. This is in part due to the relatively new nature of this treatment option and the focus on grass pollen allergies rather than tree pollen allergies (as reflected in the FDA currently only approving SLIT for grass pollen allergies) [11]. However, current research is already looking at producing more effective SLIT for tree pollen in addition to addressing many other questions that remain unclear or unanswered. As it progresses, research will certainly find more ways to further develop SLIT and other allergy treatment options, improving the quality of life for the millions who live with pollen allergies today.  

Edited by: Stephanie Chen
Illustrated by: Shanthi Deivanayagam

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