Over 25% of Canadians suffer from Allergic Rhinitis, or “Hay Fever”, affecting Quality of Life (QoL), healthcare costs & productivity while putting this population at a 2x higher risk of uncontrolled asthma (Keith et al., 2012). McMaster University researchers found that 46% of those who suffer from Allergic Rhinitis experience chronic fatigue, while 32% have trouble concentrating (Keith et al., 2012).

Uncontrolled Asthma caused by Allergic Rhinitis costs Canadians $2B annually, with costs expected to double by 2030 (Sierra-Heredia et al., 2018). This unnecessary cost is partly due to the 70,000 preventable emergency room visits, with 87% of cases caused by allergic rhinitis induced Asthma (Patel, et al 2019). Furthermore, over 80% of asthmatics are diagnosed with Allergic Rhinitis or Chronic Sinusitis (CAe0A) as triggers, which can be treated (Egan et al., 2015).

The status quo for Canadian allergy and asthma sufferers is to take symptom suppression medications such as antihistamines or corticosteroids. In a 2012 review, researchers found that 52% of sufferers default to over-the-counter antihistamines while another 36% rely on other symptom suppression medications such as Intranasal Corticosteroids (INCS) (Keith et al., 2012). These medications do not treat the cause of allergic rhinitis and are intended for short-term use, as evidenced by 61% of users reporting poor or “somewhat” control of their symptoms and 44% of users experiencing decreasing efficacy of the medication (Tachyphylaxis) within the first month of use (Keith et al., 2012)

Allergy immunotherapy, the only long-term treatment for allergies, has been proven in clinical trials and in practice globally. However, only 5% of Canadian allergy sufferers are aware of this treatment (Keith et al., 2012). In addition to lack of awareness, access is heavily hindered in Canada due to the limited availability of this treatment, with only 200 allergists in Canada offering treatment and affordability barriers. Subcutaneous Immunotherapy (SCIT), commonly known as “Allergy Shots is the primary form of allergy immunotherapy in Canada. Additionally, SCIT requires 2-3x visits to a physician’s office weekly over three years for injections.

This article will discuss how the barriers to allergy immunotherapy can be overcome for Canadian sufferers using an alternative delivery of immunotherapy, Sublingual Immunotherapy (SLIT). SLIT has been proven in clinical practice to be effective outside of North America.

Allergies are an overreaction of your body’s immune system to a harmless foreign substance that enters your body, like pollen, dust, or animal dander. Substances that cause this reaction are known as allergens. An allergic reaction occurs when an allergen enters your body, and your oversensitive immune system overreacts by producing antibodies to fight the allergen. These antibodies release histamines that result in symptoms commonly associated with allergies, such as runny nose, irritated eyes, sneezing, or swelling (AAFA, 2022).

Allergies typically develop in childhood and may re-emerge later in life. Diseases and conditions such as allergic rhinitis (CA08.0), asthma (CA23), anaphylaxis (4A84), eczema (EA80), or hives (EB05) are commonly triggered as part of an allergic reaction in the body. Allergies are typically diagnosed with the assistance of diagnostics such as Skin Prick Tests (SPTs) or an IgE blood test such as the ImmunoCAP ISAC. SPTs involve exposing your skin to various allergens in a physician’s office to identify any reactions. The ImmunoCAP ISAC test identifies and measures the antibodies in your body that fight allergens through a blood draw.

Most Canadian allergy sufferers manage their allergies through over-the-counter or prescribed symptom suppression medications, such as antihistamines and corticosteroids (i.e. Flonase®). In 2020 alone, Canadians spent over $190M on over-the-counter antihistamines (Ipsos Reid, 2021). These medications only suppress symptoms caused by allergies rather than addressing the disease itself (Chu et al., 2021).

Antihistamines such as Benadryl®, Claritin® or REACTINE® work by attempting to block the attachment of histamines to the allergen, as illustrated in Step 4 of Figure A. Antihistamines do not stop antibodies or histamines from being created in your body in the first place (Chu et al., 2021). Corticosteroids such as Flonase® and Nasacort® work acutely by countering nasal passages' swelling and mucus accumulation.

Corticosteroids are typically taken alongside antihistamines to suppress symptoms caused by allergic reactions such as congestion, irritated eyes, runny nose, post- nasal drainage, difficulty breathing, etc. (Hox et al., 2020). While initially effective, 44% of Corticosteroid users report Tachyphylaxis within their first month of use (Keith et al., 2012).

Tachyphylaxis is a medication’s weakened pharmacological response (and therefore efficacy) due to continued or repeated exposure (Webb, 2011).

Allergy immunotherapy involves the administration of allergen extracts into the patient’s body to achieve clinical tolerance of allergens that cause symptoms in patients with allergic conditions and has been proven to be effective in patients with allergic diseases and also in those who do not respond well to symptom suppression medications (Frew, 2010). The concept of immunotherapy for allergies has been around for over 100 years, with Noon’s first documentation of use with Ragweed in 1911 (Durham et al., 2011).

Biologically, allergy immunotherapy works by inciting a change in T cell subset distribution with the generation of allergen-specific T regulatory (T-reg) cells while decreasing Th2 cells. These changes naturally occur when your immune system detects exposure to an allergen. Repeated and controlled allergen exposures stimulate IL-10 and TGF-β, creating type 1 peripheral T regulatory (Tr1) cells, which act in a uterine fashion to further activate Tr1 cells, resulting in peripheral tolerance. Continued activation of Tr1 cells results in a decrease in IgE production b B cells and an increase in IgG4 and IgA levels, resulting in long-term amelioration of allergy reactions and thus symptoms (Luong, 2009). This biological reaction is similar to vaccines, which help your body’s immune system develop immunity or tolerance to an external irritant such as a virus.

Unlike symptom suppression medication such as antihistamines or corticosteroids, allergy immunotherapy has been shown to modify the underlying cause of the disease, with proven long- term benefits. Although Subcutaneous Immunotherapy (SCIT) has been the gold standard, Sublingual Immunotherapy (SLIT) has emerged over the past 30 years as an effective and safe alternative with lower barriers to treatment (Durham et al., 2016).

Allergy Immunotherapy can be administered in two ways, Subcutaneously (SCIT), where allergens are injected into the patient’s body by a clinician, and Sublingually (SLIT), where allergens are self- administered by the patient through drops sprayed under the tongue. Both SLIT and SCIT have been proven to be effective in practice for the treatment of allergies.

A recent cost minimization analysis (CMA) performed by ALK in Canada explored the direct and indirect costs of Tree Pollen Subcutaneous Immunotherapy (SCIT) in Ontario & Quebec. This analysis estimated typical indirect and direct costs for SCIT treatment in Ontario to cost $1,432.22 per year, with treatment for three years amounting to $4,233.47 over three years (Ellis, 2021).

Beyond cost, the commitment to a long-term regimen for SCIT is reported as another barrier to treatment for many Canadians. A separate study performed by Blume et al. in Canada and the US with 670 SCIT patients enrolled at 6 sites in the US and 6 sites in Canada found patient time in addition to clinical time (7-22 minutes) to be substantial, averaging 80 minutes per visit of travel time & post injection wait time. Patients reported missing half of this time worth of work. With weekly visits during the build-up phase and monthly visits during the maintenance phase, patient time is an important component of SCIT. This study concluded extract costs and patient time as the primary drivers of the cost of SCIT (Blume et al., 2015).

Due to the nature of self-administration, resulting in cost and time savings, SLIT has the opportunity to make allergy immunotherapy more accessible for 9.5M Canadians. Despite SLIT’s potential to reduce improve the quality of life (QoL) for over 9.5M Canadians while reducing the burden on Canadian healthcare systems, it has not been widely adopted. Few Canadian allergy sufferers are aware of SLIT, with most allergists & physicians opting to recommend SCIT (Keith et al., 2012).

Physicians in Canada operate on a fee-for-service model, where they are compensated for each service they provide, including office visits or administration of injections. In the CMA performed by ALK in Canada, direct costs including Physician & Consultation Billings amounted to $936.90 per year of treatment, assuming 10 titration visits in the build-up phase, and monthly visits in the maintenance stage (Ellis et al., 2021).

In contrast, those treated with SLIT would only require a single visit per year, with billings reported at $101.95. The disparity in billings is primarily attributed to the difference in the number of office visits required for SCIT vs SLIT. SCIT requires 10 weekly titration visits, followed by monthly visits in the maintenance phase while SLIT requires a single initial visit when beginning treatment, followed by a single subsequent visit for each year of treatment (Ellis et al., 2021).

SLIT has also been proven to have a better safety profile with fewer systemic reactions, and to date, no reported fatal reactions when compared to the 3.4 deaths per year in SCIT and 46.7% of SCIT patients encountering at least one systemic reaction throughout their treatment (Wise, 2012).

With regards to efficacy, multiple studies have found SLIT to be either as effective or more effective in some instances than SCIT in the reduction of symptoms and induction of long-term remission. The chart below summarizes critical findings across multiple studies reviewing the efficacy of SCIT compared to SLIT across numerous studies and systematic reviews.

SLIT for Asthma in Children

Asthma is expected to affect over 400 million people globally by 2025 and is one of the most common chronic inflammatory disorders that develop during infancy. Although not exclusively associated with allergies/atopy, 75% of children with asthma are atopic (Tsabouri, 2017). Although asthma pharmacotherapy can effectively control symptoms, asthma medication cannot affect the underlying immune response; when medication is discontinued, symptoms may recur. This is where allergy immunotherapy can come in, as the only way to interfere with the underlying immune pathophysiology causing asthma (Tsabouri, 2017).

In a study of children between the ages of three and five, researchers concluded SLIT to be both safe and effective in the reduction of symptoms relating to both allergic rhinitis and asthma (Rienzo, 2005). In contrast, SCIT is not recommended in children below the age of 5 due to safety reasons (Yang, 2021).

At the present time, specific allergy immunotherapy such as SLIT or SCIT is considered the only curative treatment for asthma, especially in pediatric asthma, where it can modify the progression of the respiratory allergic disease (Giudice, 2020).

Adherence, the degree to which a patient correctly follows a treatment plan, is primarily measured through dropout rates in allergy immunotherapy. Lower dropout rates result in better adherence, improving the efficacy of treatment. Data from a German allergy clinic indicated dropout rates for SLIT at 39%, while 32.4% of SCIT patients dropped out within the first year of treatment (Lemberg et al., 2017).

Although only 27.8% of patients who dropped out were willing to provide the reasoning for dropout, feedback demonstrated that 31% of patients dropped out due to a relocation, and 22% of patients dropped out due to difficulty remembering to continue their daily regimen (Lemberg et al., 2017).

In a recent survey of patients at a sublingual immunotherapy clinic in the US, patients expressed daily reminders and regular check-ins with coaches as the best ways to support the required daily regimen. 67% of patients reported that a mechanism for daily reminders and dosage tracking, such as a mobile app, would help them remain adherent (Appendix B).

The patient feedback collected at the American clinic is supported by a review of studies exploring whether mobile apps effectively improve treatment adherence and reduce missed doses. In the assessment of the 11 studies, adherence was found to be enhanced by up to 40% when a mobile app was used in conjunction with treatment for dose tracking and reminders. Additionally, missed doses were reduced by an average of 28%, reducing treatment time (Pérez-Jover et al., 2019).

In conclusion, patients and the Canadian healthcare system stand to benefit from a wider-spread adoption of Sublingual Immunotherapy (SLIT). There is clear evidence that SLIT is an effective treatment against allergies and associated diseases such as asthma, with the potential to reduce the $190M spent annually on unsatisfactory symptom suppression medication and the $2B burden on Canadian healthcare systems due to uncontrolled asthma triggered by preventable allergic reactions.

Substantial evidence shows SLIT as effective or more effective in some instances than SCIT. Initial evidence shows SLIT, combined with a mobile app, could result in much higher adherence. Additionally, evidence suggests SLIT is the only safe and effective curative treatment for atopic asthma in children below the age of three.