Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent edema attacks in various parts of the body, including the extremities, face, gastrointestinal tract, and airway. While most current treatments can help relieve acute symptoms pf HAE, long-term prophylactic treatment plays a critical role in minimizing attack frequency and improving quality of life. Current prophylactic options include therapies with various mechanisms of action, such as targeting C1 inhibitor replacement, kallikrein inhibition, and bradykinin pathway modulation.
To support evidence-based treatment decisions in the absence of head-to-head trials, the Value and Evidence team at EVERSANA (Sarah Walsh, Meaghan Bartlett, Elizabeth Halloran, Imtiaz Samjoo) along with the team at CSL Behring (John Sears, Yinglei Li, Maebh Kelly, Simona Gavata-Steiger, Chiara Nenci, Iris Jacobs, Ingo Pragst, Neelanjana Ray) conducted a systematic literature review and network meta-analysis (NMA) comparing the efficacy, safety, and patient-reported outcomes of long-term prophylactic treatments for HAE. In this analysis, we synthesized data from randomized controlled trials of four therapies approved for HAE prophylaxis: garadacimab, lanadelumab, subcutaneous C1 esterase inhibitor (C1INH), and berotralstat.
All therapies were found to significantly reduce HAE attack rates and improve quality of life compared to placebo, though their relative effectiveness varied. Notably, garadacimab demonstrated statistically significant reductions in time-normalized number of HAE attacks compared to lanadelumab administered every four weeks and berotralstat. Furthermore, garadacimab significantly decreased the rate of moderate to severe attacks compared to lanadelumab administered every two weeks and improved quality-of-life scores compared to berotralstat. This robust NMA can help inform clinical decision-making in the absence of direct comparative trials.
As the therapeutic landscape for HAE continues to evolve, our research contributes to a more nuanced understanding of available options, supporting clinicians in optimizing long-term management plans for their patients.
For a deeper understanding, access the Drug in R&D article here.
Author
Purva Barot is a Manager in the Evidence Synthesis group at EVERSANA, with deep expertise in systematic and targeted literature reviews, medical writing, and feasibility assessments for indirect treatment comparisons. She has contributed to…