Running header: REDUCING ALLERGIES WITH IMMUNOTHERAPY 1

Allergen-specific Immunotherapy in the Reduction of Allergy Symptoms

Keenan Fitts

University of South Florida

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Abstract

Clinical Problem: People with chronic moderate to severe allergies are at a higher risk for fatal

anaphylaxis, asthma, increased medical costs, and lead to a decreased quality of life.

Objective: This paper aims to evaluate the effectiveness and address safety implications using

allergen-specific immunotherapy (AIT) for people experiencing chronic severe allergies.

Data Sources: PubMed, EMBASE, Web of Science were accessed to obtain randomized control

studies and systematic reviews of treatments using AIT for subjects with inhalant, food, and

venom allergies. Keywords that were used were allergen immunotherapy, effectiveness of

allergen immune therapy, use of sublingual immunotherapy (SLIT), treatments of allergies using

subcutaneous injection therapy (SCIT), and safety of allergy immunotherapy.

Results: According to the World Allergy Organization (WAO) subcutaneous immunotherapy has

been effective in treating allergic rhinitis, asthma, and there is even evidence that suggest that it

can reduce the new onset of new allergies in children (2016). Consequently, there have been

reported studies of subjects experiencing anaphylaxis during the therapy and needing emergent

use of epinephrine auto-injectors. Additionally, AIT is not recommended for treatment of

medication allergies.

Conclusion: Overall, some studies show that AIT can reduce allergy symptoms by at least 50%

and has shown long-term success in treating venom allergies, inhalant allergies, and asthma.

Additionally, a study of oral immunotherapy treatment (OIT) of peanut allergies reported that

subjects were able to tolerate a dose of up to seven times their original baseline and also reported

improvement in their quality of life.

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Allergen-specific Immunotherapy in the Reduction of Allergy Symptoms

An allergy is a nondiscriminatory and chronic medical disease. Many of Americans, who

suffer from moderate to severe allergies, can experience increased stress, negative moods, and

low physical energy (Peniamina, Mirosa, Bremer & Conner, 2016). For many allergy sufferers,

over-the-counter medications and avoidance practices may not be enough, and are often costly.

According to Asthma and Allergy Foundation of America (AAFA), allergic conditions are the

fifth leading chronic disease in the US, costing $17.5 to $25 billion annually (2016). Research

also suggests that severe allergic reactions have an occurrence rate of 30% of emergency room

visits annually (Anagnostou et al., 2014). Therefore, there is also an increased concern for life-

threatening reactions such as anaphylaxis in relation to food, medications, and insect stings.

Current guidelines on managing allergies are based on taking preventive measures including

taking medications as prescribed, identifying and avoiding specific triggers (Anne-Marie &

Elias, 2015). Moreover, recommendations for acute treatment of anaphylaxis identify

epinephrine as a first-line medication followed by oxygen therapy, antihistamines, and later

consider use of corticosteroids (Anne-Marie & Elias, 2015). Allergen-specific immunotherapy is

capable of modifying a persons immune response. It is administered in conjunction with

avoidance and pharmacotherapy (WAO, 2016). This paper evaluates the effectiveness of allergy

immunotherapy as a method to treating patients with moderate to severe allergies. As a long-

term treatment, how does allergy immunotherapy in comparison to the current maintenance

medication and avoidance practices in reducing allergy symptoms in 6 months to 2 years?

Literature Search

PubMed, EMBASE, Web of Science were accessed to obtain randomized control studies,

current clinical guidelines, and systematic reviews of allergen immunotherapy and its efficacy in
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treatments. Keywords that were used were allergen immunotherapy, effectiveness of allergy

immune therapy, treatments of allergies using subcutaneous injection therapy (SCIT), and safety

of allergy immunotherapy.

Literature Review

Three randomized control trials and a review of current clinical guidelines were utilized.

Each controlled study evaluated different types of allergies with a common immunotherapy

treatment. In the first study, Anagnostou et al (2014) compared the treatment of peanut allergies

with oral immunotherapy versus the current standard of care (avoidance). This was a double-

blind study that included a sample of 85 participants who were randomly assigned to intervention

groups and placebo groups. The primary outcome showed a statistically significant decrease in

sensitivity of 62% of the subjects in the intervention group (p=0.001). Additionally, upon

completion of phase 2 of the study, two-thirds of the intervention group was able to tolerate a

dose peanuts seven times the initial starting dose. One weakness of this study was that there was

a risk of bias in that some of the participants became aware that they were receiving the active

treatment and may have under reported their symptoms. Secondly there was no long-term

follow-up to reevaluate the subjects symptoms. Strengths of the study include randomization of

subjects, use of double-blind placebo, all participants demonstrated clinical hypersensitive

reactions to peanuts, and all started with similar baseline variables.

Marogna et al. (2004) conducted a study to measure the efficacy of sublingual

immunotherapy (SLIT) and medications as a preventative treatment of allergy induced asthma;

as opposed to only using medications. The 3-year study was done as a randomized control trial

composed of 511 participants divided into intervention and control groups. Overall, the primary

outcome demonstrated improved clinical pulmonary function test (PFT) scores & metacholine
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challenges by 50%. The secondary outcome significantly reduced bronchial hyper-reactivity in

the intervention group (P < 0.0001 vs baseline). Conversely, the authors reported no significant

improvement with the control group (p=NS). There were some weaknesses noted in the trial, one

being that the study was unable to produce any information on the effect of SLIT on asthma in

comparison to adherence to current treatments. Secondly, the large sample size proved too

difficult for a long-term double-blind study and patients were aware of the treatment. As a

consequence, part of the outcome could be attributed to the placebo effect. The authors also cited

that the extreme changes in clinical scores as well as skin prick tests could not be explained by a

simple psychological effect. Strengths of the design included strict inclusion criteria, accuracy of

instruments, population size, and the length of the study.

Sola et al (2015) designed a study evaluating short-term treatment and safety of different

immunotherapy dosing regimens for SCIT. It was a 7-week double-blind randomized trial

utilizing 42 subjects divided into three parallel groups A, B, & C. The results showed 21-30%

improvement in skin reactivity for active group versus placebo but provides no statistical data.

Alternatively, there were a total of 90 mild adverse reactions out of 314 (29%) SCIT

administrations. The A-regimen accounted for only 8.5% of them and there were no life-

threatening adverse reactions; which was a major concern. The following results proved safety,

tolerability, as well as changes in immune response with short-term escalating dose regimens.

However, a few weaknesses presented against the study are the small sample size and the short-

term nature of the study does not allow for a deep statistical analysis. Also, the study was limited

to only one form of immunotherapy. Some of the strengths to this design were the strict double-

blind administration, the 3 different dosing regimens, and 3rd group for comparison.
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Anne-Marie & Elias (2015) reviewed management and prevention practices for

anaphylaxis based on the guidelines National Institutes of Health (NIH). The review focused

primarily on prevention and treatments of anaphylaxis while briefly mentioning prevalence and

diagnostic measures. Although there are no controlled studies proven efficacy of

pharmacological treatments, there is still a general consensus among experts. All practices

identify the use of epinephrine followed by antihistamines and oxygen. Also, the prevalence of

anaphylaxis in patients receiving AIT was shown to be extremely at an estimated 0.25%-1.3%

chance.

Synthesis

Anagnostou et al (2014) demonstrated an overall statistically significant decrease in

sensitivity of patients with peanut allergies (p=0.001) when utilizing OIT. In addition, Marogna

et al. (2004) used SLIT to demonstrate a 50% improvement of PFT scores and metacholine

challenges. Likewise, the outcome significantly reduced bronchial hyperactivity (P < 0.0001 vs

baseline). Sola et al. (2015) revealed that an escalating dosing regimen of SCIT could decrease

hypersensitivity from 21-30% and that the results could be safely achieved in a short time with a

proper dosing regimen. Lastly, the World Allergy Organization confirms that for patients who

are at risk for anaphylaxis due to insect stings, immunomodulation therapy might be life-saving

and greatly impact their quality of life (WAO, 2016).

Overall, the research reveals that various forms of AIT can significantly improve allergy

symptoms and the results can be achieved safely. While the research proves AIT is effective in

reducing allergy symptoms, there is still a need for larger trials to be conducted to determine its

overall safeness. Additionally, because AIT is typically a lengthy treatment, more research on the

cost benefit analysis of AIT versus long-term pharmacotherapy needs to be done.

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Clinical Recommendations

Allergen-specific immunotherapy has been its efficacy in various studies. Not only has

immunotherapy demonstrated a reduction of allergy symptoms but AIT has been proven to

prevent the onset of new sensitivities. Furthermore, research confirms that AIT can lower the

risks for anaphylaxis (long-term), reduce the patients need for pharmacotherapy, and ultimately

improve a patients quality of life. Before implementing as a standard guideline to practice, more

research needs to done evaluating the relationship between AIT and hospital/ER visits. Also

there needs to be a further investigation into the cost effectiveness of AIT.

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References

AAFA. (n.d.). Retrieved March 04, 2017, from http://www.aafa.org/page/allergy-facts.aspx

Anagnostou, K., Islam, S., King, Y., Foley, L., Pasea, L., Bond, S., . . . Clark, A. (2014)

Assessing the efficacy of oral immunotherapy for the desensitization of peanut allergy in

children (STOP II): A phase 2 randomized controlled trial. The Lancet, 383(9925), 1297-

1304. doi:10.1016/s0140-6736(13)62301-6

Anne-Marie, I., & Elias, A. G. (2015). Management and Prevention of Anaphylaxis.

F1000 Research. Retrieved March 02, 2017, from

http://europepmc.org/articles/PMC4754021

Allergen Immunotherapy for allergic rhinitis and asthma: A Synopsis. (2016). Retrieved March

03, 2017, from http://www.worldallergy.org/professional/allergic_diseases_center/

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Marogna, M., Spadolini, I., Massolo, A., Canonica, G. W., & Passalacqua, G. (2004).

Randomized controlled open study of sublingual immunotherapy for respiratory allergy

in real-life: clinical efficacy and more. Allergy, 59(11), 1205-1210. doi:10.1111/j.1398-

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Peniamina, R. L., Mirosa, M., Bremer, P., & Conner, T. S. (2016). The stress of food allergy

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doi:10.1080/08870446.2016.1143945

Sola, J., Snchez, V., Landeta, A., Madariaga, B., Martnez, A., & lvarez-Cuesta, E. (2015). A

Phase I clinical trial with subcutaneous immunotherapy vaccine of Timothy grass pollen

extract according to EMA guidelines. Immunotherapy, 7(4), 343-352.

doi:10.2217/imt.15.8