Study estimates anaphylactic risks of monoclonal antibodies used for asthma

Some monoclonal antibodies used in the treatment of inadequately controlled severe asthma may pose anaphylactic risks, according to a retrospective study of post-marking surveillance data published in Clinical and Translational Allergy.

Benralizumab (Fasenra, AstraZeneca), mepolizumab (Nucala, GlaxoSmithKline), omalizumab (Xolair; Genentech, Novartis) and reslizumab (Cinqair, Teva Pharmaceuticals) showed positive anaphylaxis signals, whereas dupilumab (Dupixent; Sanofi Genzyme, Regeneron) showed a negative signal.

Based on a lack of safety data on these five monoclonal antibodies (mAbs), researchers at Peking Union Medical College in Beijing evaluated 2,006 reports of anaphylaxis related to their use in the FDA Adverse Event Reporting System database between January 2004 and September 2020.

Researchers noted that most of the patients in these cases were young and middle-aged adults, with five to 10 times as many females as males in the cases related to omalizumab, benralizumab and mepolizumab, and all four cases related to reslizumab occurring in females. Children and older adults accounted for a small number of patients.

The duration of each drug’s market availability impacted the distribution of adverse report dates. Omalizumab, which has been available for nearly 20 years, had the most anaphylaxis cases, with reports increasing each year.

Additionally, although all five of the mAbs were used mainly for patients with asthma, omalizumab also was used for chronic urticaria, and dupilumab was used for atopic dermatitis.

The researchers used reporting OR (ROR), proportional reporting ratio (PRR), information component (IC), and empirical Bayes geometric mean (EBGM) algorithms to analyze anaphylaxis signals for the five mAbs.

Omalizumab had the highest of each these metrics. In fact, 1,773 of the cases (88.4%) were related to omalizumab. When drug use was considered in these cases, patients with asthma were more likely to have life-threatening outcomes than patients with chronic urticaria (18% vs. 12.9%; P = .022).

The researchers estimated the risk for anaphylaxis with omalizumab to be between 0.1% and 0.2%, whereas the risk for anaphylaxis with reslizumab in clinical trials was approximately 0.3%. The FDA has issued a black box warning for both drugs.

Benralizumab, mepolizumab and reslizumab also had positive anaphylactic reaction signals but with relatively lower ROR, PRR, IC and EBGM. However, researchers noted patients receiving benralizumab have experienced hypersensitivity reactions, including anaphylaxis.

Also, patients receiving omalizumab, benralizumab and reslizumab should be kept informed and have a post-injection observation period due to their relatively higher ROR, according to the researchers.

Although there were no cases of drug-related anaphylaxis during clinical trials of mepolizumab, it had a low but positive anaphylaxis signal, with a recently reported case of anaphylaxis following its administration.

Dupilumab was the only mAb with completely negative signals, possibly due to its degree of humanization, the researchers wrote. With 99% human components, dupilumab was the only fully human mAb of the five examined. The other four are humanized mAbs with 90% human components.

“Anaphylaxis reactions to humanized mAbs are not so common, but still exist because of the persistent immunogenicity caused by using transgenic cell lines ... however, fully human mAbs do not have this defect,” the researchers wrote, adding that this supports dupilumab’s self-administration at home.

Although the risk for death following anaphylaxis was low for all five mAbs, anaphylaxis following omalizumab was associated with disability in 14 cases.

Also, the researchers noted no significant difference in the proportion of life-threatening events among the five mAbs, but the benralizumab group had a significantly higher risk for initial or prolonged hospitalization due to anaphylaxis than the omalizumab group (42.86% vs. 28.92%, P = .024).

Overall, the data suggest female sex and those using the agents for asthma may be risk factors for anaphylaxis.

The results may be limited because the data were mined from a voluntary self-reporting system, and the recorded anaphylactic events were not well standardized, the researchers wrote. Also, mAbs with longer post-marketing periods tended to have more reported adverse events.

“As this was a real-world study that analyzed post-marking surveillance data, its results would be more representative of real experience in clinical practice than those of clinical trials,” the researchers wrote, adding that additional research is necessary to verify the results.