Desensitization regimen can help manage anaphylaxis to Myozyme
Severe allergic reaction to Myozyme seen in 30% of children in small study
Anaphylaxis, a severe allergic reaction, occurred in nearly one-third of children with Pompe disease treated with the enzyme replacement therapy Myozyme (alglucosidase alfa) in a small study.
However, rapid desensitization regimens — using small doses initially and then increasing the doses — safely re-established tolerance to Myozyme in the long term. The treatment is sold as Lumizyme in the U.S.
The study, “Long-Term Experience with Anaphylaxis and Desensitization to Alglucosidase Alfa in Pompe Disease,” was published in the International Archives of Allergy and Immunology.
ERT’s lab-made proteins increase risk of anaphylaxis
Pompe disease is mainly treated with enzyme replacement therapy (ERT), whereby a lab-made supply of acid alpha-glucosidase (GAA), the enzyme missing in Pompe patients, is infused directly into the bloodstream. Without GAA, the complex sugar molecule glycogen builds up to toxic levels in body tissues, especially muscle.
Because ERT contains lab-made proteins, some Pompe patients have an increased risk of anaphylaxis — a severe life-threatening allergic reaction against these proteins. Symptoms include breathing difficulties, irregular heartbeat, low blood pressure, nausea, dizziness, and skin lesions.
However, studies reporting the occurrence of anaphylaxis in Pompe are limited to case reports.
To re-establish tolerance to ERT after an anaphylactic episode, patients can receive rapid drug desensitization in which ERT is restarted at very low doses and increased to a target dose by doubling it every 15–30 minutes over a few hours. However, data are also limited on the effects of desensitization with ERT.
In the study, researchers in Turkey reviewed the medical records of Pompe children treated with the ERT Myozyme to evaluate the frequency, clinical features, and management of anaphylaxis, and to assess those who underwent desensitization with Myozyme.
All 14 reviewed patients were diagnosed with the more severe infantile-onset type of Pompe disease, except for one with juvenile (late-onset) Pompe. The age of diagnosis ranged from 1-40 months (3.3 years), and nine children (64.3%) were girls. One patient died before starting ERT, and six of the 13 who received Myozyme died due to Pompe-related causes.
Anaphylaxis to Myozyme reported in 4 of 13 children in study
Anaphylaxis was reported in four of the 13 cases (30.8%), of which three were considered severe and one moderate. No record of other medicinal allergies among the patients and their families was noted. One patient and her mother had a history of asthma.
Desensitization regimens with Myozyme were used in these four cases and started with an initial dose ranging between 500,000 and 1,000,000 times lower than the target dose. All children continued a desensitization regimen with diluted ERT.
A total of 390 desensitization sessions were conducted, with a follow-up between 12 and 129 months (almost 11 years). Among the patients, one developed skin hives during the first two desensitization sessions (0.5%). The researchers found no differences between those who experienced anaphylaxis and those who didn’t in terms of sex, age at diagnosis, the start of ERT, its dose, and treatment frequency.
“Anaphylaxis with [Myozyme] is not rare in [Pompe disease] patients,” the team concluded. “Desensitization with [Myozyme] is safe and effective in the long term.”
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