Lanadelumab increases attack-free rates in hereditary angioedema patients
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Key takeaways:
- Lanadelumab reduced median HAE attack rates by 98.8%.
- Over 70% of patients increased their dosing interval.
- The mean time to a dosing interval increase was 8.2 months.
Lanadelumab effectively improved attack-free rates of type I and II hereditary angioedema patients, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice.
In previous trials, lanadelumab (Takhzyro, Takeda) reduced the frequency and severity of hereditary angioedema (HAE) attacks, Markus Magerl, MD, of the Institute of Allergology, Charité - Universitätsmedizin Berlin and the Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, and colleagues wrote.
The study team’s primary objective was to examine the effectiveness of lanadelumab on the attack-free rate (AFR) of patients with HAE.
Methods
This observational, retrospective medical chart review study took place at 19 sites in Germany (n = 6), France (n = 7), Austria (n = 3) and Greece (n = 3). Data was extracted between Sept. 15, 2021, and June 29, 2022. Patients had to be aged at least 12 years, have type I or type II HAE and have started long-term prophylactic (LTP) treatment with lanadelumab between August 2018 and May 2021.
Data collection occurred during the pre-index and post-index periods. The pre-index period began 12 months prior to the start of treatment and the post-index period ended at treatment discontinuation.
Collected data were pseudonymized and included patient demographics, HAE history and life-threatening attack history from time of HAE diagnosis to 1 day prior to index initiation. Data on comorbidities, HAE attack characteristics and HAE therapies were collected for 12 months prior to index initiation. Post-index data consisted of treatment patterns, HAE attack characteristics and on demand therapy use for HAE attacks.
The primary outcome included AFRs of patients taking lanadelumab every 2 weeks or every 4 weeks. HAE attack severity was categorized as mild, moderate or severe.
Results
In total, the study included 198 patients (98% adult; 61.6% female). The mean age at lanadelumab initiation was 43.4 years, and most patients had type I HAE (91.9%).
A family history of HAE was discovered in 143 patients (72.2%), whereas a history of life-threatening HAE attacks before treatment was found in 60 patients (30.8%) with a mean number of attacks of 4.8 (standard deviation [SD], 8.2).
In the pre-index period, 196 patients (99%) used on-demand treatment and 118 (59.6%) used LTP. The number of patients that switched to lanadelumab from a previous therapy was 103 (52%). More than one type of LTP was used by 11 patients (5.6%) prior to index initiation.
At least one HAE attack was experienced by all patients pre-index with a mean of 35.8 (SD, 33.2) attacks per person. The HAE attacks mostly affected extremities (n = 140; 70.7%) and the abdomen (n = 166; 83.8%), whereas laryngeal attacks were found in 31 patients (15.7%).
Pre-index HAE attack severity was mild for 109 patients (55.1%), moderate for 130 (65.7%) and severe for 99 (50%). An attack with unknown severity was found in 52.5% of patients and a life-threatening attack was experienced by 15 patients (7.6%).
A total of 82 patients (41.4%) began lanadelumab because of a lack of response to other HAE prophylactic therapy, 42 patients (21.2%) due to a lack of disease control before on-demand therapy and 48 patients (24.2%) started it because of an anticipation of efficacy.
The total length of time that patients took lanadelumab varied from a single dose to 43.6 months of treatment, with a median of 28.8 months. Lanadelumab was still taken by 96% of patients at the end of the follow-up period. The most common reasons for the discontinuation of lanadelumab were a patient’s decision (n = 2; 1%), tolerability (n = 1; 0.5%), pregnancy (n = 3; 1.5%) and moving (n = 1; 0.5%).
An increase in lanadelumab dosing intervals occurred in 144 patients (72.7%) with eight patients (5.6%) increasing from every 2 weeks to every 15 or 16 days, 38 patients (26.4%) increasing from every 2 weeks to every 17 or 18 days, 69 patients (47.9%) increasing to every 3 weeks, 25 patients (17.4%) to every 4 weeks, one patient (0.7%) increasing to every 6 weeks and three patients (2.1%) increasing to every 8 weeks.
The mean time to an increase was 8.2 months. Of the 144 patients that increased dosing intervals, reasons included a patient being attack-free (n = 119; 82.6%) or having an improved condition or sufficient maintenance (n = 28; 19.4%).
Within the post-index period (43.6 months), 120 patients (60.6%) had at least one HAE attack, with the time to the first attack ranging from less than 1 week to 158 weeks.
The pre-index monthly AFRs ranged from 16.2% to 28.3%, whereas post-index AFRs ranged from 82.7% to more than 95%. Cumulative AFRs improved to 54.4% 12 months post-index and 39.4% post-index with a median 28.8-month duration. Cumulative AFR in the second year of treatment was 59.8% and 69.6% in the third year.
The median monthly number of HAE attacks pre-index was 2.2 per person (interquartile range [IQR], 1-4) whereas post-index the number was 0 (IQR, 0-0.2). Lanadelumab significantly reduced the median HAE attack rate by 98.8% (P < .0001) compared with pre-index rates.
Among patients with an increase in dosing interval, the pre-index cumulative AFR was 0% and then 50% in the post-index period. The mean time from index to an HAE attack was higher in patients who increased their dosing interval compared with patients without an increase (34 vs. 25.3 weeks). The timing between an HAE diagnosis and treatment initiation was also higher among patients with an interval increase compared with those without (22.2 vs. 17.9 years).
Magerl and colleagues noted that these study results give insight into treatment patterns and the increase of dosing intervals when patients are stable and attack-free.
Perspective
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These findings are not surprising, but are significant in that they support the other pivotal trials from lanadelumab that demonstrate safety and efficacy and improved attack-free rates for HAE patients. It is very much in line with my experience and clinical practice. I actually wrote the first lanadelumab prescription in the United States, so I have a long track record with this medication, and the results are consistent with what I have seen clinically in the real world. When it hit the market in the U.S. several years ago, it changed the landscape of how we approach HAE patients and long-term prophylactic therapy. It was a game changer in a great way. This study supports the current body of literature and, hopefully, lanadelumab will provide patients a safe and effective option for preventing HAE attacks and give them more of a sense of normalcy in their lives.
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Magerl M, et al. J Allergy Clin Immunol Pract. 2024;doi:10.1016/j.jaip.2024.12.008.
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