HAE Prophylaxis Options Show High, Comparable Long-Term Adherence

Patients with hereditary angioedema (HAE) receiving berotralstat, lanadelumab, or subcutaneous plasma-derived C1 inhibitor (SC-pdC1-INH) had high, similar adherence and persistence rates.1

“Rates of berotralstat adherence and persistence were comparable with those of lanadelumab or SC-pdC1-INH,” wrote investigators led by Bruce L. Zuraw, MD, a professor in the division of Allergy and Immunology at the University of California, San Diego in La Jolla, California.

Investigators recognized the lack of data comparing targeted long-term HAE prophylaxis treatments and sought to assess adherence and persistence after initiation of berotralstat, lanadelumab, or SC-pdC1-INH. The team leveraged electronic health records linked to claims data and included 357 participants aged ≥ 12 years initiating berotralstat (n = 90), lanadelumab (n = 189), or SC-pdC1-INH (n = 78) between June 22, 2017, and September 12, 2023. Participants had ≥ 12 months of continuous enrollment before and after initiating long-term prophylaxis.

The primary outcome was adherence, defined as the mean proportion of days covered, and persistence, describing no treatment gap ≥ 45 days after long-term prophylaxis initiation. Investigators also conducted a subgroup analysis among patients with ≥ 2 claims for long-term prophylaxis, as well as a sensitivity analysis by reassigning cohorts based on the first claim for qualifying long-term prophylaxis after June 22, 2017.

The treatments had similar adherence rates: berotralstat (0.73), lanadelumab (0.78), and SC-pdC1-INH (0.74). Over 12 months, 66% on berotralstat, 69% on lanadelumab, and 67% on SC-pdC1-INH were adherent. These adherence rates were greater than average adherence rates across treatments for other chronic diseases, which range from 40% to 50%.

Berotralstat, lanadelumab, and SC-pdC1-INH also had similar persistence rates 12 months post-treatment initiation: 61%, 58%, and 53%, respectively. This was lower than the persistence rates at 3 months, ranging from 73% to 89%.

“This decrease may theoretically be due to patients stopping their index medication, losing coverage during a transition in insurance or the annual prior authorization process, or having a positive response to treatment and moving to a lower dosing frequency,” investigators explained.

The subgroup and sensitivity analyses also supported the similar high adherence and persistence rates of these HAE treatments. The percentage of patients with ≥ 2 fills was high (≥ 80%), with no significant difference between treatments.

“Because those cohorts were likely enriched with patients who were responsive to their index medication, it is unsurprising that adherence and persistence were higher in the two or more fills subgroup analysis than in the main analysis,” the team wrote.

The sensitivity analysis also showed similar treatment patterns between cohorts. However, previous long-term prophylaxis use was lower among patients who were indexed on berotralstat or lanadelumab than on SC-pdC1-INH.

Since lanadelumab and SC-pdC1-INH were approved before berotralstat, investigators reasoned that lower prophylaxis use is not attributable to a lack of options but indicates a preference for oral HAE medications or less frequent injections. They noted that a 2018 survey found 98% of patients on injectable long-term prophylaxis—and all patients not on it—would try an oral option if available.2 Research has previously shown reasons for discontinuing long-term prophylaxis include adverse events, low attack frequency, medication not working, preference for on-demand treatment, anxiety about long-term use, and healthcare provider recommendation.3

“The similarity in treatment patterns across cohorts reinforces the recommendation from the international European Academy of Allergy and Clinical Immunology/World Allergy Organization guidelines that the choice of [long-term prophylaxis] should be individualized and based on shared decision-making between patients and their health-care professionals,” investigators concluded.1

References

1. Zuraw BL, Lopez-Gonzalez L, Manjelievskaia J, Winer I, Dean A, Wall S, Nelson J, Nestler-Parr S, Gillard P, Christiansen SC. Adherence and persistence among patients with hereditary angioedema receiving long-term prophylaxis in the United States. Allergy Asthma Proc. 2025 Apr 29. doi: 10.2500/aap.2025.46.250029. Epub ahead of print. PMID: 40300843.

2. Geba D, Mohd Sani J, Gascon M, Hahn R, Aggarwal K, Rosselli J. Hereditary angioedema patients would prefer newer-generation oral prophylaxis. J Drug Assess. 2021 Jan 6;10(1):51-56. doi: 10.1080/21556660.2020.1863699. PMID: 33489436; PMCID: PMC7801100.

3. Mendivil J, DerSarkissian M, Banerji A, Diwakar L, Katelaris CH, Keith PK, Kim H, Lacuesta G, Magerl M, Slade C, Smith WB, Choudhry Z, Simon A, Sarda SP, Busse PJ. A multicenter chart review of patient characteristics, treatment, and outcomes in hereditary angioedema: unmet need for more effective long-term prophylaxis. Allergy Asthma Clin Immunol. 2023 May 29;19(1):48. doi: 10.1186/s13223-023-00795-2. PMID: 37248521; PMCID: PMC10227962.