Anaphylaxis Risk Varies Among Monoclonal Antibodies in Patients With Severe Asthma

New research based on real-world data largely aligns with the scientific literature, although one monoclonal antibody—dupilumab—stood out for its very low risk.

Patients receiving monoclonal antibodies (mAbs) for severe asthma need to be monitored closely due to an increased risk of anaphylaxis, according to new study findings.

The report, published in Clinical and Translational Allergy, found 4 out of 5 common mAbs were associated with a heightened anaphylaxis risk, though the risk varied from therapy to therapy.

Results pertain to a small percentage of patients with hard-to-control asthma.

“Despite extensive efforts, there is still a small proportion of patients with severe asthma insufficiently controlled with high‐dose inhaled corticosteroids and are oral corticosteroid‐dependent,” explained the study’s investigators, including corresponding author Bin Zhao, MD, of Peking Union Medical College Hospital in China.

In such cases, mAbs like benralizumab (Fasenra), dupilumab (Dupixent), mepolizumab (Nucala), omalizumab (Xolair), and reslizumab (Cinqair) can be used as add-on maintenance.

However, Zhao and colleagues noted that there remain significant open questions about the risk of anaphylaxis in patients receiving these mAbs. They noted that real-world data for omalizumab differed from pre-approval clinical trials, and other mAbs have also been linked with cases of anaphylaxis.

Zhao and colleagues wanted to comprehensively examine anaphylaxis risk in patients with asthma using real-world data. To do so, they consulted the FDA’s Adverse Event Reporting System database, looking for instances of anaphylaxis among patients taking one of the 5 mAbs between January 2004 and September 2020. They found a total of 2006 cases.

Cases tended to occur in young and middle-aged adults, and females were much more likely than men to suffer from anaphylaxis (1403 cases vs 293 cases; in 310 cases, the patient’s gender was not available in the data). The primary indication for which the mAbs were prescribed was asthma, although the drugs were also prescribed to treat other conditions, most commonly chronic urticaria.

Given that the 5 mAbs had been on the market for different lengths of time, the investigators used multiple types of analyses to estimate anaphylaxis risk.

“The Bayesian analysis and non-proportional analysis found that omalizumab, benralizumab, reslizumab, and mepolizumab showed positive signals for anaphylaxis, while only dupilumab showed a negative signal,” they reported.

The rates of anaphylaxis broadly aligned with previous literature, with omalizumab carrying an anaphylaxis risk of between 0.1% and 0.2%, and reslizumab carrying a risk of approximately 0.3%. Zhao and colleagues noted that both drugs carry black box warnings.

The authors said benralizumab has been linked with hypersensitivity reactions, including anaphylaxis. They said patients taking omalizumab, benralizumab, and reslizumab should therefore be observed following injection for possible adverse events.

In the case of mepolizumab, Zhao and colleagues said it also had a “low but positive” anaphylaxis signal. This differed from clinical trials, in which no cases of drug-related anaphylaxis were reported. The authors said increased attention should be given to mepolizumab, given the contradiction between clinical trials and real-world evidence.

Dupilumab, on the other hand, appears to have the lowest risk of anaphylaxis, a fact Zhao and colleagues suggested may be due to its higher degree of humanization (99% human component, compared to 90% for the other 4 medications).

“Anaphylaxis reactions to humanized mAbs are not so common, but still exist because of the persistent immunogenicity caused by using transgenic mouse cell lines, which cannot generate human carbohydrate side chains,” Zhao and colleagues wrote. “However, fully human mAbs do not have this defect.”

They said the positive safety profile of dupilumab suggests it is a good candidate for self-administration at home.


Li L, Wang Z, Cui L, Xu Y, Guan K, and Zhao B. Anaphylactic risk related to omalizumab, benralizumab, reslizumab, mepolizumab, and dupilumab. Clin Transl Allergy. Published online June 3, 2021. doi:10.1002/clt2.12038