Hereditary angioedema (HAE) is a rare genetic disorder that causes recurrent swelling of the skin, mucous membranes, or various internal organs at irregular intervals. International guidelines recommend long-term prophylaxis with lanadelumab or berotralstat as first-line therapy. The INTEGRATED trial evaluated the efficacy of lanadelumab and the effects of extending the dose interval in a real-world setting.
In the etiology of hereditary angioedema (HAE), the kallikrein-kinin system and the end product of this metabolic pathway, bradykinin, play a central role. The effects of lanadelumab – a fully humanized monoclonal antibody – are based on binding to plasma kallikrein, thereby reducing the formation of bradykinin. In Switzerland and other European countries, lanadelumab (Takhzyro®) is approved for the prophylaxis of recurrent attacks of HAE in patients over 12 years of age. The recommended starting dose is 300 mg every two weeks (q2w). “If patients are seizure-free, the administration interval can be extended to four weeksa,” explained Prof. Markus Magerl, MD, Allergie-Centrum-Charité-Universitätsmedizin Berlin. In addition, the INTEGRATED study demonstrated that individualized extension to other of the dose intervals also works (Fig. 1).
a Dose interval 4 weeks=q4w
Adjustment of the dose interval of lanadelumab during the course of the study.
The study included 198b patients over 12 years of age with HAE type I or II who had started long-term prophylaxis (LTP) with lanadelumab from November 2017 to October 2021. Of these, 182 (91.9%) had HAE type I and 16 (8.1%) had HAE type II. The mean age was 43.4 years, 61.6% were female, and 30.8% had a history of life-threatening attacks. The mean number of seizures at baseline was 35.8 over a 12-month period. The median treatment duration with lanadelumab was 28.8 months (interquartile range: 20.4-35.7). 96% of patients were still being treated with lanadelumab at the end of data collection. When looking at dose intervals, it is noticeable that 6 months after starting lanadelumab LTP, 30% of patients had already switched to an interval >2 weeks. 9.1% had an interval of four weeks and 8.1% had one of 3 weeks; 12.2% switched to a different interval. As the study progressed, the q2w dose interval was extended in an increasing number of patients (Fig. 1) . 36 months after Baselinec, the proportion of those with a 2-week interval was only 26.7%. “The others had longer intervals – most of them four weeks, some three weeks, eight weeks or other intervals,” the speaker said.
b Germany n=76, France n=86, Austria n=14, Greece n=22
c before initiation of lanadelumab LTP.
Conclusion: Lanadelumab improved seizure freedom
Primary endpoints included the efficacy of lanadelumab on cumulative and monthly seizure-free rate (AFR) and the effect of increasing the dose interval (q2w) on AFR. The final analysis suggests that lanadelumab LTP significantly improves AFR. Monthly AFRs ranged from 16.2% to 28.3% during the pre-index event period and from 82.7% to 84.8% thereafter (months 1 and 2), reaching as high as >95% (months 26, 36, 38, 39, and 41+). None of the patients had life-threatening seizures after the index event.
d Index event = onset of lanadelumab LTP.
Source: “Real-world Effectiveness of Lanadelumab in European Patients with HAE Type I/II: Results from the Retrospective INTEGRATED Study,” Prof. Markus Magerl, MD, Flash Talks 000786. EEACI Annual Meeting, 9–11 June 2023.
DERMATOLOGIE PRAXIS 2023; 33(4): 25
| Cover image: LucyHAE, wikimedia |
