Matching-adjusted indirect comparison between garadacimab and lanadelumab for the long-term prophylactic treatment of patients with hereditary angioedema
Bibliographic record
Abstract
Aim: This study aimed to estimate the relative efficacy between garadacimab 200 mg once monthly (200 QM) and two dosing regimens of lanadelumab (300 mg once every 2 weeks [300 Q2W] and 300 mg once every 4 weeks [300 Q4W]) in adolescent/adult patients with hereditary angioedema (HAE) using matching-adjusted indirect comparisons (MAICs), in the absence of head-to-head randomized controlled trials. Materials & methods: Individual patient data were available from the phase II ( NCT03712228 ) and the phase III VANGUARD ( NCT04656418 ) trials investigating garadacimab, and published summary-level data from the phase III HELP trial investigating lanadelumab ( NCT02586805 ). The primary outcome was time-normalized number of HAE attacks. Secondary efficacy outcomes included time-normalized number of HAE attacks requiring on-demand treatment, time-normalized number of moderate and/or severe HAE attacks, and proportion of attack-free patients. Quality of life (QoL) was also assessed via change from baseline in AE-QoL total score. Results: Compared with lanadelumab 300 Q2W, garadacimab 200 QM statistically significantly reduced number of moderate and/or severe HAE attacks (rate ratio [RR]; 95% confidence interval: 0.25; 0.07, 0.84) and improved AE-QoL score (mean difference: -17.38; -33.67, -1.08). Compared with lanadelumab 300 Q4W, garadacimab 200 QM showed statistically significant improvements in all outcomes: HAE attacks (RR: 0.29; 0.13, 0.63), attacks requiring on-demand treatment (RR: 0.29; 0.13, 0.66), moderate and/or severe HAE attacks (RR: 0.15; 0.05, 0.49), proportion of attack-free patients (hazard ratio: 3.25; 1.45, 7.29), and AE-QoL score (mean difference: -21.29; -37.39, -5.18). Conclusion: These MAICs showed improved efficacy and QoL with garadacimab compared with lanadelumab across multiple endpoints. These findings demonstrate that garadacimab may provide improved therapeutic benefit compared with lanadelumab in the long-term prophylactic treatment of patients with HAE.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".