Analysis of icatibant for the treatment of laryngeal hereditary angioedema attacks in the FAST-3 study
Bibliographic record
Abstract
The efficacy and safety of icatibant for the treatment of edematous hereditary angioedema (HAE) attacks was established in three Phase III trials, including the For Angioedema Subcutaneous Treatment-3 study (FAST-3; NCT00912093). Here, data from the double-blind, controlled phase and open-label extension (OLE) of FAST-3 were analyzed post-hoc to specifically evaluate icatibant for the treatment of laryngeal attacks, which can cause potentially fatal airway obstruction. Controlled phase: adults with HAE type I/II were randomized to a single subcutaneous injection of icatibant 30 mg or placebo for their first mild-to-moderate laryngeal attack or moderate-to-very severe cutaneous/abdominal attack; severe laryngeal attacks were treated with open-label icatibant. OLE: attacks were treated with up to three icatibant injections, at ≥6-hour intervals. Three outcomes were analyzed for first icatibant-treated laryngeal attacks: 1) time to onset of symptom relief (earliest of three consecutive measurements for which there was a 50% reduction of patient–assessed 5-symptom composite 100 mm visual analog scale [VAS]); 2) time to almost complete symptom relief (earliest of three consecutive measurements for which all VAS symptom scores <10 mm); 3) patient- and investigator-assessed time to initial symptom improvement. Reinjection rates were also recorded. For first icatibant-treated laryngeal attacks in the controlled phase or OLE (n=27), median (95% CI) time to onset of symptom relief was 2.0 (1.5-3.5) hours, median (95% CI) time to almost complete symptom relief was 6.0 (3.0–24.3) hours, and median (95% CI) patient- and investigator-assessed time to initial symptom improvement was 0.7 (0.4-0.9) and 0.8 (0.5-1.1) hours, respectively. In the OLE, 41/43 (95.3%) laryngeal attacks were treated with one icatibant injection, 2/43 (4.7%) were treated with two injections, and none required three injections. Icatibant provided symptom relief for mild-to-severe laryngeal HAE attacks in FAST-3. In the OLE, almost all laryngeal attacks were treated with one injection only.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.007 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".