Hereditary angioedema attacks fall nearly 95% with lanadelumab among adolescents
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Key takeaways:
- 95.2% of the patients completed 30 months or more of treatment.
- The mean change in quality-of-life score was –21.4 points.
- Patients who had not used lanadelumab before saw greater improvements.
Adolescents with hereditary angioedema experienced fewer attacks, improved quality of life and treatment satisfaction with lanadelumab, according to a study published in Annals of Allergy, Asthma & Immunology.
Treatment was safe and tolerable as well, Timothy Craig, DO, clinical researcher, allergy, asthma and immunology, departments of medicine, pediatrics and biomedical sciences, Penn State University, and colleagues wrote.
The study included 21 adolescents (mean age, 14.3 years; 47.6% girls) aged 12 to 17 years with type 1 (n = 18; 85.7%) or type 2 hereditary angioedema (HAE). Symptom onset developed at a mean age of 7 years.
The cohort included eight patients who rolled over from the HELP OLE study, which assessed the use of lanadelumab (Takhzyro, Takeda) in adolescents over 26 weeks, and 13 patients who had never used the biologic.
Patients began the new study with a single 300 mg subcutaneous dose of lanadelumab. They did not receive a second dose until after they had a confirmed HAE attack. Single 300 mg doses then followed every 2 weeks.
Twenty of the patients (95.2%) completed 30 or more months in the study, with an overall mean of 32.4 months. Eight patients (38.1%) completed the full study. Twelve (57.1%) withdrew because they transitioned to commercial lanadelumab outside of the study, and one (4.8%) was lost to follow-up.
The mean HAE attack rate fell from 1.58 a month at baseline to 0.11 a month at the end of the study for a mean reduction of 94.7%. Specifically, rates fell from 1.65 to 0.2 a month for the rollover patients (–90.9%) and from 1.54 to 0.06 a month (–97.1%) in the patients who had never used lanadelumab before.
Eight patients (38.1%), including two of the rollover patients and six of the new patients, did not experience any attacks during treatment. Mean percentages of attack-free days included 99.1% overall, 98.2% for the rollover patients and 99.6% for the lanadelumab-naïve patients. Also, patients experienced a mean attack-free period of 18.4 months, with a mean maximum duration of 24 months.
All the rollover patients, 92.3% of the lanadelumab-naïve patients and 95.2% of the overall cohort experienced a treatment-emergent adverse event, led by upper respiratory tract infections (n = 6; 28.6%). The researchers characterized most of the treatment-emergent adverse events as mild or moderate.
Almost all treatment-emergent adverse events reported by the 12 patients (57.1%) who experienced them pertained to the injection site, with 11 patients (52.4%) reporting 227 instances of mild or moderate injection site pain.
None of the treatment-emergent adverse events related to treatment were serious or severe, nor were they adverse events of special interest or causes of study discontinuations. There were no deaths due to treatment-emergent adverse events either.
Mean Angioedema Quality of Life Questionnaire (AE-QoL) scores fell from 27.5 at baseline to 7.5 at the end of the study, for a mean change of –21.4 that the researchers called a clinically meaningful improvement in health-related quality of life.
The change was much larger for the lanadelumab naïve group compared with the rollover group (–29 vs. –6.1), the researchers continued, although both were considered minimal clinically important differences.
The lanadelumab naïve group also had consistently higher mean changes in each domain on the AE-QoL than the rollover group, including fatigue/mood (–20.4 vs –10), fear/shame (–30.2 vs. 2.8), functioning (–39.6 vs –16.7) and nutrition (–28.4 vs –2.1).
The researchers also categorized EuroQoL 5 Dimensions 5 Levels scores as stable through the study and said there was a slight improvement in 12-item Short Form Health Survey scores from the HELP OLE baseline to the end of the study.
Patients further perceived their disease as under control based on Angioedema Control Test scores at the end of HELP OLE. The rollover and lanadelumab naïve groups both reported normal levels of anxiety and depression at the HELP OLE baseline and at the end of the study. Work Productivity and Activity Impairment Questionnaire-General Health scores saw a slight improvement from the HELP OLE baseline to the end of the study as well.
Patients also were satisfied with treatment, with the nine-item Treatment Satisfaction Questionnaire for Medication scores of 88.9 from the rollover group and 93.6 from the lanadelumab naïve group for effectiveness, 75.4 from the rollover group and 83.3 from the lanadelumab naïve group for convenience, and 86.7 from the rollover group and 90.7 from the lanadelumab naïve group for global satisfaction.
These findings indicate that lanadelumab effectively provided long-term prophylaxis for adolescents with HAE with clinical improvements in health-related quality of life and high satisfaction with treatment, the researchers concluded.
Perspective
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This study is not surprising, but it is significant in that it shows evidence of a viable treatment option for adolescents with HAE where, in times past, there have not been great options available.
These findings also are consistent with what we have seen in the adult population and with my patients. Lanadelumab has performed consistently in the original clinical trials and in the open label extension studies that look at more of the long-term safety and efficacy.
My favorite part of the study was its focus on quality of life among adolescents. When I think of chronic diseases, I consider the burden of disease and burden of treatment and the impact those have on patients.
HAE is known to have a high disease burden on patients, and it also has a high burden of treatment. Metrics such as quality of life are reasonable measures of this, and lanadelumab improved that overall burden in adolescents.
This will be significant as these adolescents move forward in their life. It would be interesting to follow the adolescents over time to see what impact the improved HAE and QOL has on their education, careers and psychosocial health.
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