Immunotherapy for Cat Allergies: A Potential Strategy to Scratch Back

Introduction

Cat allergies are a common and costly problem in the United States. According to a survey from the American Pet Products Association, it is estimated that there are 85.8 million pet cats in the United States and of the 65% (79.7 million) of households in the United States with pets, 35% (42.9 million households) owned at least 1 cat. ¹ As many as 3 in 10 people with allergies have allergic reactions to cats and dogs with cat allergies occurring twice as frequently. ²

Felines produce a protein called Felis domesticus allergen 1 (Fel d 1), which is the major cat allergen affecting pet dander suffers. Fel d 1 is found primarily in cat skin and hair follicles and is produced in sebaceous, anal, and salivary glands. ³ The clinical symptoms associated with cat allergy include mild rhinitis, conjunctivitis, allergic inflammation, and even life-threatening asthmatic responses requiring epinephrine.

Pharmacotherapy is intended to alleviate and control symptoms once allergic disease has developed. The common pharmacologic options available to target inflammation symptoms are antihistamines, topical and systemic corticosteroids, mast cell stabilizers, leukotriene antagonists, β-adrenergic agonists, and monoclonal anti-IgE antibodies. ⁴ Literature indicates that antihistamines can alleviate worsening allergic rhinitis and maintain peak expiratory flow rates superior to placebo in allergic individuals undergoing a cat allergen challenge. ⁵ Inhaled corticosteroids are also effective in relieving allergy symptoms and are recommended as first line therapy by the Allergic Rhinitis and its Impact on Asthma (ARIA) group and the International Primary Care Respiratory Group (IPCRG) for allergic rhinitis in which nasal congestion is predominant.^6-8

While these medications can temporarily mask allergy symptoms, they do not treat the underlying condition. Many allergy sufferers would prefer not to use long-term anti-allergy medication to relieve symptoms. Various non-drug therapies exist to prevent or treat symptoms associated with cat allergies. The Environmental Assessment and Exposure Control guidelines describe 2 methods for dealing with allergen exposing pets: source control and abatement. Source control involves using measures to reduce occupant exposure to the allergen by complete removal of the animal. As an alternative, several US-based companies market “hypoallergenic” cats and dogs. Hypoallergenic cats are genetically altered to not produce Fel d 1, but remain problematic to allergy sufferers due to the other cat allergens they produce (albumin, cystatin, lipocalin, immunoglobulin A, immunoglobulin M, latherin, etc). There have been no studies that have shown conclusively that cats can be truly hypoallergenic.^9,10

Abatement involves the removal of or reducing exposure to contaminated materials that act as reservoirs in the home. This includes acts such as the use of HEPA (high-efficiency particulate arrestance) filters, vacuuming, chemically treating carpet, and the use of mattress encasements. ⁹ Unfortunately, cat allergens are the most prevalent pet allergens found and can even be detected in areas where cats do not live. ¹¹ One study showed that airborne Fel d 1 can be detected in virtually all homes with cats and lower concentrations can be found in roughly 30% of homes without cats. ¹² Because of this, there is a clear need for additional measures to alleviate and prevent allergic symptoms.

Immunotherapy is one therapeutic option that reduces the need for long-term medication administration and works to reduce the underlying allergic response. The purpose of this manuscript is to describe the efficacy and safety of immunotherapy when used to prevent or treat cat allergies.

Allergen-Specific Immunotherapy

The goal of allergen-specific immunotherapy (AIT) is to desensitize the patient to a particular allergen and induce immune tolerance through exposure to gradually increasing doses of the allergen itself. ⁴ Current AIT guidelines recommend patients for immunotherapy when their symptoms are not adequately controlled by medications and/or avoidance measures, when adverse effects of medications are unacceptable, or when the patient wants to reduce their long-term use of medication. ¹³

AIT has an 85% to 90% success rate at improving allergic symptoms and generally requires 3 to 6 months before symptom relief is noted. ¹⁴ It may take up to 12 to 24 months before full benefits are evident. Optimal duration of therapy has yet to be determined; however, studies suggest a minimum treatment period of 3 to 5 years.^14-16 Duration of treatment must be individualized based on the nature of the allergic problem, the rate and completeness of recovery, and whether symptoms return when immunotherapy is discontinued. ¹⁴

The two common methods of AIT administration are subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). A recent consensus report on updates on allergy immunotherapy, suggest both routes of administration are effective in reducing symptom scores for seasonal and perennial allergens, increase quality of life, and decrease the need of other medication. ¹⁷

Subcutaneous Immunotherapy Therapy

SCIT dates back to 1911 and can be a very effective means to help control allergy symptoms and prevent disease progression.^18,19 Traditional SCIT therapy requires multiple, frequent visits to a healthcare provider for injections and observation. Common practice is to administer 1 or 2 sets of subcutaneous injections a week starting at low doses (1:10 000 dilution) and titrating up to effective therapeutic ranges. Once maintenance dosing is achieved, the injection interval is gradually spread from every 2 weeks to every 4 weeks. ²⁰ In the case of cat allergens, the solution for injection is typically composed of 10 000 bioequivalent allergy units (BAUs) per milliliter (standardized extract) of lyophilized cat hair and dander added to glycerol and human serum albumin (0.03%). Effective maintenance doses are suggested in the 1000 to 4000 BAU range. ²¹

A systematic review by Abramson et al ²² evaluated 88 trials with 3459 asthmatic patients exposed to SCIT. The therapy resulted in significant reduction in asthma symptoms, medication use, and improvement in bronchial reactivity. The study found that for every 3 patients treated with subcutaneous immunotherapy, 1 case of deterioration in asthma symptoms was avoided (95% CI, 3-5) and that for every 4 patients treated, 1 patient would avoid increasing symptomatic medication use (95% CI, 3-6).

A second study found that SCIT therapy can reduce the need for systemic steroids in patients with allergic rhinitis. ²³ The retrospective evaluation of a Danish National Registry Database found that the mean annual steroid injections were 1.6 in patients not receiving SCIT and 1.0 in the SCIT group (P < .0001). The study also found that 84% of patients treated with SCIT did not require systemic steroids during treatment and 72% remained off steroid therapy after SCIT treatment completion. For the group receiving SCIT therapy, risk of receiving a steroid injection after SCIT treatment completion was lowest for those individuals receiving 1 year of immunotherapy with gradually increasing risk as duration of therapy increased. The authors interpret this finding to mean that the reduction in need for systemic therapy occurs only in those patients who respond appropriately to SCIT therapy within the first 3 years of treatment.

SCIT is not without risk. The World Allergy Organization has a grading system to classify the severity of allergic reaction. A grade 1 reaction refers to 1 organ system symptom/sign present and the highest grade, grade 5, refers to the death of a patient. ¹³ The American College of Allergy, Asthma, and Immunology and the American Academy of Allergy, Asthma, and Immunology (ACAAI/AAAAI) Immunotherapy Safety Survey reported that between 2008 and 2012, 1 confirmed fatality occurred among 23.3 million injection visits. ²⁴ The same survey found a 0.1% rate of SCIT-related systemic allergic reactions and that the rate for very severe (grade 4) reactions was 1 per 1 million injections. Generally, near-fatal or severe reactions are rare and most reactions are local in nature (redness, pruritus, swelling at injection site). ¹³

Allergy shots are not effective for food allergies or people with chronic hives. They are not recommended for people with severe uncontrolled asthma or heart problems, especially those taking beta blockers or ACE inhibitors as taking these medications may mask symptoms of anaphylaxis. Allergy shots should be avoided during pregnancy, but may be continued during pregnancy if started before conception and approved by a physician. ¹⁴

Sublingual Immunotherapy

SLIT typically requires daily administration with antigen drops or tablets held under the tongue for several minutes followed by either spitting out the allergen solution or absorbing/swallowing the sublingual tablet. ²⁵ Sublingual therapy is initiated with a full dose or a short escalation in dose, with the first dose given under medical supervision. ²⁶ The total dose of allergen administered via SLIT in 1 year is usually 20 to 200 times larger than the dose needed for SCIT. ²⁷

The efficacy of SLIT has been demonstrated by Alverez-Cuesta et al, ²⁵ where SLIT-treated patients experienced significant improvements in all symptom scores (total, nasal, bronchial, and ocular) and peak expiratory flow (PEF) readings (P < .05) versus placebo during natural exposure challenge. There were no local or systemic reactions reported and of the 17 withdrawals from the study, none were due to an adverse reaction. SLIT therapy, like SCIT therapy, has also been shown to reduce asthma symptoms, exacerbations, and use of inhaled corticosteroids in asthma-sensitive patients.^28-30

There are currently only 3 immunotherapy tablets in the United States with Food and Drug Administration (FDA) approval (2 targeting grass pollen and 1 targeting ragweed pollen). ²⁶ Other forms of SLIT may be prescribed off-label, but do not receive insurance coverage.

SLIT is generally considered to have a more favorable safety profile compared with SCIT. ³¹ Allergen exposure through sublingual tissue is less likely to cause anaphylaxis than SCIT.^31,32 SLIT therapy is contraindicated in patients with a history of eosinophilic esophagitis and those with severe, unstable or uncontrolled asthma. ²⁶ Patients with oral inflammation (thrush, ulcers, lichen planus) or oral wounds (from dental procedures, tooth extractions, etc) should temporarily discontinue therapy due to a potentially enhanced risk for anaphylaxis and all patients should be prescribed epinephrine for self-injection per manufacturer recommendation. ³³

Conclusion

Both SCIT and SLIT are valuable measures for those with cat allergies. Both routes of administration are effective in reducing symptom scores for seasonal and perennial allergens, result in an increase quality of life, and decrease the need of other medications. ¹⁷ Both routes of administration require multiple administrations that may take years to desensitize. SCIT is more invasive, requires frequent office visits, and has greater possibility of severe reaction. SLIT can be administered at home, and has a lower risk of anaphylaxis, but often requires daily administration and may not be covered by insurance. Both are effective immunologic options that can make a positive impact in reducing allergic symptoms for pet lovers and cat dander sufferers alike.