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December 03, 2024
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Patients with hereditary angioedema down-titrate lanadelumab, maintain symptom control

Fact checked byKristen Dowd
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Key takeaways:

  • Median time between initiation of lanadelumab treatment and first reduction was 6.5 months.
  • Researchers said that down-titration may be considered with well-controlled symptoms.

BOSTON — Patients with hereditary angioedema may down-titrate lanadelumab treatment while exhibiting symptom control, according to a poster presented at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting.

The goal of the study “was to examine real-world treatment patterns and characteristics of patients with hereditary angioedema (HAE) who receive treatment with lanadelumab (Takhzyro, Takeda),” Maureen Watt, MS, director, global evidence and outcomes, Takeda Development Center Americas, told Healio.

Lanadelumab doses after first titration included 300 mg once every 4 weeks (86.7%), 300 mg once every three weeks (8%) and 5.3% once every 6 weeks (5.3%).
Data were derived from Watt M, et al. Real-world patterns of lanadelumab down-titration in patients with hereditary angioedema. Presented at: ACAAI Annual Scientific Meeting; Oct. 24-28, 2024; Boston.

Previous research

A previous real-world study of 186 patient charts with the same objective found a numerical reduction in HAE attack rates following drug initiation with low discontinuation rates and reductions in dosing frequency primarily due to well-controlled disease.

Maureen Watt

During this study, patients experienced a mean of 0.8 ± 1.2 attacks per month before treatment and 0.1 ± 0.3 attacks per month after starting treatment.

“Overall, 62.9% of patients remained on lanadelumab 12 months after initiation,” Watt said. “Eight (4.3%) patients had discontinued lanadelumab at the time of chart abstraction.”

However, 20 patients in the original 150-patient cohort initiated treatment with 300 mg of lanadelumab every 2 weeks with a reduction to doses of 300 mg every 4 weeks during the observation period.

“Therefore, it was the findings of the previously reported study cohort that prompted this real-world study of dosing in patients who initiate lanadelumab 300 mg every 2 weeks and then reduce their lanadelumab dosing frequency,” Watt said.

Current study

The current chart review included 75 patients (mean age, 32.7 years; 44% male; 66.7% white) with type 1 or 2 HAE with a mean time from diagnosis to index date of 3.6 years. Also, 26.7% of the cohort had experience with long-term prophylaxis for their disease.

The researchers who performed the chart extraction included allergists and immunologists (91%), and 78% of them were based in the community.

Patients began their treatment with 300 mg doses of lanadelumab once every 2 weeks between 2018 and 2023. First reductions in dosing frequency included 300 mg once every 4 weeks for 86.7% of the patients, 300 mg once every 3 weeks for 8%, and 300 mg once every 6 weeks for 5.3%.

Two patients reduced their dosing from every 3 weeks to every 4 weeks. One patient reduced dosing frequency from every 4 weeks to every 6 weeks. Another patient reduced dosing frequency from every 4 weeks to every 8 weeks. None of the patients increased their dosing frequency.

“The study found that in both the initial dose period of lanadelumab and the reduced dosing frequency period, there was an overall reduction in attack rates and severity of the attacks,” Watt said. “Additionally, health care resource utilization decreased.”

The median time to dosage reduction was 6.5 months (95% CI, 5.1-7.4), with 98.7% (n = 74) of reductions attributed to good disease control, which persisted after doses were reduced as indicated by a mean monthly attack rate of zero.

“This was maintained after dosage reduction,” Watt said.

Among 67 patients with follow-up data for 12 months or more, 91% stayed on lanadelumab at 12 months. Among 36 patients with follow-up data for 24 months or more, 97.2% stayed on lanadelumab at 24 months.

Conclusions, next steps

Based on these findings, the researchers said that lanadelumab provides flexibility in dosing regimens so patients can maintain good disease control and consider down-titration when their disease is well controlled.

“As this was a physician chart review, the study was limited in the planned data collection to data in a predefined case report form, which could be completed within 45 minutes per patient chart,” Watt said.

Watt also noted that this study was a retrospective chart review, so she and her colleagues could not collect data at multiple points in time to adequately track the progress of HAE control and improvements in these patients.

“Incorporating recent findings into how physicians care for patients with HAE is really about understanding and adapting to the patients’ diverse needs,” Watt said.

“It is important for physicians to understand the characteristics of patients who will respond well on every 4-week dosing,” she continued. “In this study, patients had been well-controlled (ie, attack-free) on every 2-week dosing for at least 6 months and had a lower baseline attack rate.”

The researchers are now developing a manuscript of the study, which will be submitted to a peer-reviewed journal early next year.