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Principles of immunotherapy for allergic rhinitis: Assess benefits and risks, check for response, consider patient preference

Presenter: Theodore M. Freeman, MD, San Antonio.

Evolution of Immunotherapy for Allergic Rhinitis. Presented April 29, 2023.


Candidates for immunotherapy for the treatment of allergy are those patients who present with an appropriate clinical condition with evidence of specific IgE antibodies by either skin testing or in vitro testing and test results that are consistent with the clinical symptoms. Appropriate clinical conditions include allergic rhinitis, allergic asthma, and Hymenoptera hypersensitivity. Other allergic conditions that may be amenable to immunotherapy are food hypersensitivity and atopic dermatitis, said Theodore M. Freeman, MD, allergist-immunologist from San Antonio, who presented the principles of immunotherapy.

The mechanisms by which immunotherapy exerts its effects are a reduction in end-organ response to an allergen resulting in decreased early and late phase response of the skin, conjunctiva, nasal mucosa, and bronchi; decreased allergen-induced eosinophil, basophil, and mast cell infiltration; blunting of mucosal priming, and a reduction of bronchial sensitivity to histamine. Humoral responses are noted as well, although these don’t correlate consistently with clinical response.

Benefits and risks to immunotherapy should be assessed. Check the patient’s response to avoidance of the allergen, if possible, medications the patient is taking, the effectiveness of prior treatments (ie, nasal steroids, antihistamines), patient preferences for treatment, and the severity of the disease.

“If they’re still candidates, we offer them immunotherapy,” he said. He uses stock allergenic extracts starting with a 10-fold dilution of the lowest-dose vial (vial #1), with injections once or twice weekly, eventually building to 0.5 mL. This process is repeated for vials #2, #3, and #4, which contain increasing concentrations of the allergenic extract. The maintenance dose is generally considered 0.5 mL of vial #4 “and it often takes several months to get to that maintenance dose,” he said.

The risk of immunotherapy is severe reaction (anaphylaxis), with an estimated fatality rate of 0.2 per 1 million tests. “We recommend keeping everyone in the office for 30 minutes to monitor for a severe reaction,” said Dr. Freeman. “Don’t forget that the management of anaphylaxis is epinephrine.”

The patient should be reassessed for clinical response and reactions every 6 to 12 months, as well as compliance with the immunotherapy schedule. “If they’re not compliant, there's no reason to continue immunotherapy and give them that intermittent risk [of reactions],” he said. “Generally, we have a three-strike rule; if they’ve had three severe reactions, you don’t want to keep going, but certainly you want to make sure they’re having a good response. If they’re not having a good response after being on the maintenance dose for a year, you need to reassess that patient to see if they have new antigens or why they’re not responding to the immunotherapy.”

With a good response, continue immunotherapy for 3 to 5 years, and then take a trial off immunotherapy and monitor for symptoms in the event that the patient is cured. “There’s no way to tell that unless we stop and see what happens,” he said.

Improving convenience

The problems with immunotherapy are twofold: the delivery system, as described, is cumbersome and the risk of anaphylaxis. To improve convenience, sublingual immunotherapy may be tried. The dose of allergen is larger with the sublingual versus the subcutaneous route. “You need 5, 10, to 20 times as much as given subcutaneously if you’re going to use those extracts for sublingual immunotherapy,” he said. “You have to do it every other day at least,” which increases the cost significantly, perhaps as high as $500 per month to perform sublingual immunotherapy.

Also, the extracts in the test kit are approved by the U.S. Food and Drug Administration (FDA) only for use in subcutaneous immunotherapy, so insurance coverage is lacking for sublingual immunotherapy. “You have to have patients that are really dedicated and have a lot of expendable income,” said Dr. Freeman. A sublingual tablet has been approved by the FDA but only for ragweed, northern pasture grasses (ie, timothy), and dust mites. The tablets are placed under the tongue for 1 to 2 minutes and then swallowed as they dissolve. This process is repeated from 3 days a week to as often as daily. The tablets are discontinued when the allergy season is over. As with other forms of immunotherapy, “we have to begin 12 weeks before the season and continue it throughout the season,” he said.

While anaphylaxis is not a risk with sublingual immunotherapy, patients often report symptoms in the oropharynx (ie, pruritus/swelling, irritation) and upper and lower gastrointestinal tract (ie, nausea, vomiting, diarrhea, heartburn).

Improving safety

To improve the safety of immunotherapy, consider premedication with omalizumab, advised Dr. Freeman. Omalizumab pretreatment has been shown to improve the safety and tolerability of cluster and rush immunotherapy schedules in patients with moderate persistent asthma and allergic rhinitis, respectively. Additionally, omalizumab used in combination with immunotherapy has been shown to be effective in improving symptom scores compared with immunotherapy alone.

Disclosures

Theodore M. Freeman, MD has no relationships with entities whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

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