Combination therapy helps control allergic reaction to ERT for Pompe
Case report: Allergy medicine omalizumab added to desensitization protocol
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Combining the allergy medicine omalizumab with a desensitization protocol helped a 40-year-old woman with Pompe disease overcome a persistent allergic reaction to enzyme replacement therapy (ERT), according to a case report.
People with Pompe disease who experience hypersensitivity, or allergic reactions, to ERT often undergo desensitization, a strategy that gradually increases the ERT dose to help the body adapt to the medication. However, when this is ineffective, there are few other therapeutic options. In this case, adding omalizumab (sold as Omlyclo and Xolair) to the desensitization therapy ultimately controlled the allergic reactions.
“This integrated … approach ultimately enabled the safe continuation of full-dose ERT without recurrence of hypersensitivity, providing a practical and reproducible framework for managing similarly complex cases,” researchers wrote.
The study, “Combined omalizumab and desensitization to control IgE-mediated hypersensitivity in enzyme replacement therapy for late-onset Pompe disease,” was published in the Orphanet Journal of Rare Diseases.
Immune system sometimes attacks version of GAA provided by ERTs
Pompe disease is a genetic condition that leads to a lack of, or a faulty, acid alpha-glucosidase (GAA) enzyme. GAA typically breaks down certain complex sugar molecules. Without enough working GAA, these molecules can build up in cells, leading to a variety of symptoms.
Treatment for Pompe disease typically relies on ERT, medications that provide the body with a working version of GAA. In the U.S., approved ERT options include Lumizyme (alglucosidase alfa, sold as Myozyme in Europe) and Nexviazyme (avalglucosidase alfa; Nexviadyme in Europe). Both are given as intravenous (into-the-vein) infusions every two weeks.
Sometimes, a patient’s immune system attacks the version of GAA provided by ERTs, leading to potentially severe allergic reactions. Immune cells called basophils, which also play a role in other types of allergies, trigger these mistaken attacks. A class of antibodies called immunoglobulin E (IgE) also contributes to the response.
“Although the overall safety profile of [Myozyme] and [Nexviadyme] is favorable, IgE-mediated reactions may occur even after years of uneventful infusions, abruptly threatening treatment continuity and patient outcomes,” the researchers wrote.
Woman was on ERT for 11 years before having an allergic response
The team from Italy described the case of a 40-year-old woman with Pompe disease who had been taking Myozyme without side effects for about 11 years. She then developed hives, swelling, throat tightness, and low blood pressure after a dose, suggesting an allergic response.
First, the woman’s clinicians tried giving her anti-inflammatory medications before ERT dosing. This was unsuccessful, and she had similar reactions that required emergency treatment with epinephrine.
To confirm that this was an allergic reaction, the team exposed a blood sample to Myozyme and measured basophil activity. The results of the basophil activation testing (BAT) suggested that she had indeed developed an IgE-related allergic reaction to the medication.
Based on this finding, they initiated a desensitization protocol that consisted of 15 steps over 10 hours until the full therapeutic dose was administered.
“Desensitization protocols represent the mainstay of management in patients with recurrent or severe [hypersensitivity reactions] who cannot otherwise continue ERT,” the team noted. “Rapid drug desensitization induces a temporary state of tolerance by administering the culprit drug in escalating doses through multiple steps and bags with increasing concentrations.”
For a few months, desensitization before each Myozyme dose successfully prevented allergic reactions. The woman then developed a breakthrough reaction, with hives and low blood pressure.
Although breakthrough reactions may occur despite optimized protocols, desensitization remains the cornerstone strategy for maintaining access to life-saving therapy.
At this point, the woman’s doctors suggested switching to Nexviadyme. BAT analysis of Nexviadyme suggested that the woman might be allergic to this medication as well. Rather than starting at a full dose, the team maintained the previously used desensitization protocol and added the immunosuppressant methotrexate.
However, a few months later, another breakthrough reaction occurred. Given the persistent hypersensitivity, the clinical team decided to administer an injection of omalizumab, which targets IgE. Two days later, they went through another round of Nexviadyme desensitization without any reactions.
Over the following months, they gradually shortened the desensitization protocol until the woman was able to start infusions from the full-dose solution.
“This stepwise increase minimized the risk of severe reactions during the reintroduction phase,” the researchers wrote.
She was ultimately able to start receiving full-dose (20 mg/kg) Nexviadyme infusions without desensitization. BAT analysis showed reduced basophil activation, suggesting that the combined approaches successfully reduced the allergic response. She reported an improvement in her quality of life with no further interruptions to ERT.
“Although breakthrough reactions may occur despite optimized protocols, desensitization remains the cornerstone strategy for maintaining access to life-saving therapy,” the researchers wrote. This case supports the desensitization approach, with the addition of omalizumab as a potential option for patients who continue to experience allergic responses.
The team also noted that regular BAT analysis allowed them to monitor the woman’s allergic responses with a simple blood test. This could be a helpful approach when directly exposing a patient to a possible allergy-triggering medication is deemed too risky, the scientists noted.
