REVISED ASSESSMENT OF ATTACK-FREE OUTCOMES IN HEREDITARY ANGIOEDEMA: AN UPDATED NETWORK META-ANALYSIS OF PROPHYLACTIC TREATMENTS
Author(s)
Yinglei Li, PHD1, Simona Gavata-Steiger, MBA, MPH2, Imtiaz Samjoo, BSc, MSc, PhD3, Erin Kodis, PHD1, Nicolas Scheuer, MSc2.
1CSL Behring, King of Prussia, PA, USA, 2CSL Behring AG, Bern, Switzerland, 3EVERSANA, Victoria, BC, Canada.
1CSL Behring, King of Prussia, PA, USA, 2CSL Behring AG, Bern, Switzerland, 3EVERSANA, Victoria, BC, Canada.
OBJECTIVES: To compare the relative efficacy of approved long-term prophylactic (LTP) treatments in clinical use for achieving attack-free status in patients with hereditary angioedema (HAE) using an updated network meta-analysis (NMA).
METHODS: A Bayesian NMA was conducted based on a systematic literature review of randomized controlled trials (RCTs) evaluating approved LTP therapies for HAE (PROSPERO protocol #CRD42022359207). HAE attacks and follow-up duration were defined by each study, and attack-free status was assessed from the start of treatment. The updated approach modelled attack occurrence directly using a binomial complementary log-log model, with a maximum follow-up offset to adjust for differing trial durations; the estimated baseline hazard and hazard ratio were converted to the probability of remaining attack-free over a common 26-week horizon, reported as relative risk (RR). Both random- and fixed-effects models were evaluated given the sparse network. Treatments were also ranked using probability of being best (P-best) and surface under the cumulative ranking curve (SUCRA).
RESULTS: All evaluated LTP treatments were associated with higher proportions of attack-free status versus placebo. Garadacimab 200 mg QM was associated with substantial improvements in attack-free status versus all selected comparators across analyses. In the random-effects analysis, garadacimab showed improved attack-free outcomes versus lanadelumab 300 mg Q2W (RR [95% CI]: 2.46 [1.20-11.25]), lanadelumab 300 mg Q4W (3.81 [1.50-29.54]), subcutaneous C1 esterase inhibitor 60 IU/kg BIW (5.23 [1.66-74.07]), donidalorsen 80 mg Q4W (4.37 [1.61-25.53]), donidalorsen 80 mg Q8W (7.10 [1.86-194.67]), and berotralstat 150 mg QD (36.77 [3.54-7495.85]). Garadacimab also ranked highest based on P-best (98.6%) and SUCRA (99.7%). Results were consistent in fixed-effects analyses.
CONCLUSIONS: Unlike the previous NMA, this updated analysis accounts for the greater opportunity to experience an attack with longer observation periods. Garadacimab 200 mg QM may increase the likelihood of remaining attack-free by 2.5-36 fold versus other HAE LTP therapies.
METHODS: A Bayesian NMA was conducted based on a systematic literature review of randomized controlled trials (RCTs) evaluating approved LTP therapies for HAE (PROSPERO protocol #CRD42022359207). HAE attacks and follow-up duration were defined by each study, and attack-free status was assessed from the start of treatment. The updated approach modelled attack occurrence directly using a binomial complementary log-log model, with a maximum follow-up offset to adjust for differing trial durations; the estimated baseline hazard and hazard ratio were converted to the probability of remaining attack-free over a common 26-week horizon, reported as relative risk (RR). Both random- and fixed-effects models were evaluated given the sparse network. Treatments were also ranked using probability of being best (P-best) and surface under the cumulative ranking curve (SUCRA).
RESULTS: All evaluated LTP treatments were associated with higher proportions of attack-free status versus placebo. Garadacimab 200 mg QM was associated with substantial improvements in attack-free status versus all selected comparators across analyses. In the random-effects analysis, garadacimab showed improved attack-free outcomes versus lanadelumab 300 mg Q2W (RR [95% CI]: 2.46 [1.20-11.25]), lanadelumab 300 mg Q4W (3.81 [1.50-29.54]), subcutaneous C1 esterase inhibitor 60 IU/kg BIW (5.23 [1.66-74.07]), donidalorsen 80 mg Q4W (4.37 [1.61-25.53]), donidalorsen 80 mg Q8W (7.10 [1.86-194.67]), and berotralstat 150 mg QD (36.77 [3.54-7495.85]). Garadacimab also ranked highest based on P-best (98.6%) and SUCRA (99.7%). Results were consistent in fixed-effects analyses.
CONCLUSIONS: Unlike the previous NMA, this updated analysis accounts for the greater opportunity to experience an attack with longer observation periods. Garadacimab 200 mg QM may increase the likelihood of remaining attack-free by 2.5-36 fold versus other HAE LTP therapies.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
CO80
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Rare & Orphan Diseases, Systemic Disorders/Conditions (Anesthesia, Auto-Immune Disorders (n.e.c.), Hematological Disorders (non-oncologic), Pain)