Tezacaftor/ivacaftor in people with cystic fibrosis who stopped lumacaftor/ivacaftor due to respiratory adverse events
Bibliographic record
Abstract
Background Increased rates of respiratory adverse events have been observed in people ≥12 years of age with cystic fibrosis homozygous for the Phe508del- CFTR mutation treated with lumacaftor/ivacaftor, particularly in those with percent predicted forced expiratory volume in 1 s (ppFEV 1 ) of <40%. We evaluated the safety, tolerability, and efficacy of tezacaftor/ivacaftor in people with cystic fibrosis homozygous for Phe508del- CFTR who discontinued lumacaftor/ivacaftor due to treatment-related respiratory signs or symptoms. Methods Participants ≥12 years of age with cystic fibrosis homozygous for Phe508del- CFTR with ppFEV 1 of ≥25% and ≤90% were randomized 1:1 and treated with tezacaftor/ivacaftor or placebo for 56 days. Results Of 97 participants, 94 (96.9%) completed the study. The primary endpoint was incidence of predefined respiratory adverse events of special interest (chest discomfort, dyspnea, respiration abnormal, asthma, bronchial hyperreactivity, bronchospasm, and wheezing): tezacaftor/ivacaftor, 14.0%; placebo, 21.3%. The adverse events were mild or moderate in severity. None were serious or led to treatment interruption or discontinuation. Overall, the discontinuation rate was similar between groups. The mean (SD) ppFEV 1 at baseline was 44.6% (16.1%) with tezacaftor/ivacaftor and 48.0% (18.1%) with placebo. The posterior mean difference in absolute change in ppFEV 1 from baseline to the average value of days 28 and 56 was 2.7 percentage points with tezacaftor/ivacaftor vs placebo. Conclusions Tezacaftor/ivacaftor was generally safe, well tolerated, and efficacious in people ≥12 years of age with cystic fibrosis homozygous for Phe508del- CFTR with ppFEV 1 of ≥25% and ≤90% who previously discontinued lumacaftor/ivacaftor due to treatment-related respiratory signs or symptoms.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".