
Asthma patients treated with the biologic drug, omalizumab, may experience delayed, hypersensitivity reactions. Specifically, a new study found a link between the drug and serum sickness, which is an immune-complex-mediated hypersensitivity reaction that classically presents with fever, rash, polyarthritis or polyarthralgias.
The link was discussed in the case study, “Serum Sickness-Like Reaction Secondary to Omalizumab,” and was and presented at the 2024 CHEST Annual Meeting in Boston. The poster presentation followed the case of a 45-year-old woman with severe asthma and allergic bronchopulmonary aspergillosis. She was on omalizumab for five years before symptoms emerged. Her symptoms resolved after switching to the drug tezepelumab.
Kathryn Hughes, MD, MPH, DAvMED
Although rare, the researchers noted, serum sickness and serum sickness-like reactions may occur with the use of omalizumab (Xolair) and other biologic medications.
“We look for type 1 hypersensitivity reactions in our clinic and for injection reactions, and we think a little bit less about these more delayed reactions,” Dr. Hughes told Healio. “I think it’s something to keep an eye out for.”
In addition to omalizumab, the patient was being treated with a fluticasone, umeclidinium and vilanterol inhaler as well as fexofenadine and omeprazole. A physical exam and self-reporting indicated the patient was experiencing monthly arthralgias, debilitating malaise, low-grade fevers and abdominal discomfort. The patient experienced these symptoms within a few days of her monthly omalizumab treatment. They would improve gradually within a week.
“Along this time, she had experienced gradual worsening of her chronic symptoms of cough, wheezing and urticaria as well, which had been previously well controlled for the past five years,” Dr. Hughes said.
Her providers suspected a serum-like sickness reaction and changed therapy from omalizumab to tezepelumab (Tezspire). The arthralgias, malaise and abdominal discomfort all resolved once omalizumab was discontinued.
“We gave her a short course of oral clinical steroids for treatment of an asthma exacerbation and noted that her respiratory symptoms, as well as all of her joint symptoms, dramatically improved,” Hughes said. “Then her respiratory symptoms gradually became controlled over the course of three doses.”
According to Dr. Hughes, serum sickness presents as immune complex depositions in various organs. It manifests in a wide range of reactions including fevers, rashes and constitutional symptoms as well as vasculitis and renal and other organ failures.
Serum sickness-like reactions are less understood in the immunology literature, she said, but appear to be less severe.
“They tend to have relatively normal labs and no organ damage,” Dr. Hughes said. “And they, in research, at least, have not identified immune complexes. So, it is difficult to tease out what exactly is driving that.”
Serum sickness and serum sickness-like reactions both tend to resolve once treatment with the offending drug has ceased, she said. The researchers do not recommend rechallenges if treatment must stop.
“You can use steroids to help bridge those symptoms until that drug is out of the system,” Dr. Hughes said. “In some mild cases, you can try to continue the drug if it’s still efficacious.”
In literature describing reactions with omalizumab and dupilumab (Dupixent), most of the sparse case reports describe reactions with the two drugs, Dr. Hughes said. This may be the case because they have been available longer, she said.
Dr. Hughes cautioned that there are no data suggesting that if a patient develops serum sickness in response to one biologic, it will develop in response to other drugs too. She also said that these reactions, although rare, can be seen with all monoclonal antibodies.
Dr. Hughes said this case was notable because the patient had developed these reactions after being well controlled for five years without any of these symptoms. If the patient would have presented with these symptoms after the second dose of omalizumab, the serum sickness would have been very difficult to identify, she said.
“Like, are these just side effects of the medication? Or is this more of an immunologic phenomenon?” Hughes said. “The fact that she developed them after five years would suggest more of an immunologic phenomenon.”