Repeat dosing needed for about 1 in 7 treated HAE attacks, study finds
Abdominal and multisite attacks were more likely to need retreatment
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About 1 in 7 treated swelling attacks in people with hereditary angioedema (HAE) required an additional dose of on-demand medication, with attack severity and treatment characteristics emerging as the main factors associated with retreatment, according to a real-world study from the Czech Republic that examined more than 8,000 HAE attacks.
Researchers found that abdominal attacks and attacks affecting multiple parts of the body were more likely to require repeated treatment. They also found that attacks initially treated with the approved on-demand therapy Firazyr (icatibant) were more likely to need an additional dose than those treated with C1 inhibitor (C1-INH) therapies, although they cautioned that differences in attack severity or other clinical factors may have influenced this finding.
“These findings may help anticipate attacks requiring repeated dosing and support individualized treatment strategies,” the researchers wrote.
Retreatment common in real-world data
The study, “Registry-Based Analysis of Treatment and Retreatment Attacks of Hereditary Angioedema,” was published as a research letter in Clinical & Experimental Allergy.
HAE is most often caused by genetic mutations that affect the production or function of a protein called C1 esterase inhibitor (C1-INH). When C1-INH is missing or faulty, the body produces too much of the signaling molecule bradykinin, causing fluid to leak from blood vessels into surrounding tissues. This leads to recurrent episodes of swelling that can affect the hands, feet, face, airways, or digestive tract, with abdominal attacks often causing severe pain.
Acute HAE attacks are treated with on-demand medications. These include C1 inhibitor (C1-INH) therapies, which replace the missing or faulty C1-INH protein to help reduce bradykinin levels and control swelling. Examples of on-demand C1-INH therapies include Berinert (human C1 esterase inhibitor) and Ruconest (recombinant C1 esterase inhibitor). Other C1-INH therapies, such as Cinryze (human C1 esterase inhibitor) and Haegarda (human C1 esterase inhibitor), are used to help prevent HAE attacks.
Another option is Firazyr, which works by blocking the effects of bradykinin.
“Although these therapies are generally effective, some attacks require repeated treatment,” the researchers wrote. “However, real-world data identifying predictors of retreatment remain limited.”
Registry study analyzed 8,448 attacks
To determine how often HAE attacks require retreatment and identify factors associated with repeated dosing, researchers analyzed data from the Czech national registry of primary immunodeficiencies, which includes essentially all diagnosed HAE patients in the country.
The study examined 8,448 attacks reported by 175 patients between March 2012 and September 2023, including 7,001 attacks in 167 patients treated with on-demand therapy. Retreatment was defined as receiving another dose of the same or a different on-demand therapy within 48 hours for the same attack.
Overall, 1,024 treated attacks (14.6%) in 101 patients required retreatment. Another 1,447 attacks (17.1%) were not treated, likely because symptoms were mild, resolved on their own, treatment was unavailable, or patients chose not to treat them.
Firazyr was the most commonly used first-line treatment, accounting for nearly two-thirds (63.7%) of treated attacks. Of these, 17.3% required additional treatment within the same attack episode. Plasma-derived C1 inhibitor (C1-INH) therapy was used to treat 17.8% of attacks, with 5.6% requiring further treatment. Recombinant human C1-INH therapy was used in 13.7% of attacks, of which 15.6% required repeated treatment.
Attack severity linked to retreatment
After accounting for differences in patients and attack characteristics, abdominal attacks were about twice as likely to require retreatment as attacks without abdominal involvement. The likelihood of retreatment also increased as more parts of the body were affected during a single attack, suggesting that more extensive or systemic activation of the bradykinin pathway may contribute to attacks that are more difficult to control, according to the researchers. Older age was associated with a slightly lower likelihood of requiring an additional dose.
Treatment type was also associated with retreatment. Compared with Firazyr, attacks initially treated with either plasma-derived or recombinant human C1 inhibitor (C1-INH) therapies were less likely to require another dose. According to the researchers, the drugs’ different pharmacological properties may partly explain these findings. For example, Firazyr has a relatively short half-life, which may contribute to higher retreatment rates.
However, they cautioned that treatment was not assigned randomly, meaning differences in attack severity or other clinical factors may also have influenced the results, limiting any conclusions about cause and effect.
“Our results confirm that retreatment is relatively common in real-world management of HAE, occurring in approximately 15% of treated attacks,” the researchers wrote, adding that “both disease severity and treatment characteristics influence the likelihood of repeated dosing during HAE attacks.”
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