Improved Clinical Outcomes During Long-term Osilodrostat Treatment of Cushing Disease With Normalization of Late-night Salivary Cortisol and Urinary Free Cortisol
Bibliographic record
Abstract
Purpose: To assess whether simultaneous normalization of late-night salivary cortisol (LNSC) and mean urinary free cortisol (mUFC) in patients with Cushing disease treated with osilodrostat is associated with better clinical outcomes than control of mUFC or LNSC alone. Methods: Pooled data from two phase III osilodrostat studies (LINC 3 and LINC 4) were analyzed. Both comprised a 48-week core phase and an optional open-label extension. Changes in cardiovascular/metabolic-related parameters, physical manifestations of hypercortisolism, and quality of life (QoL) were evaluated across the following patient subgroups: both LNSC and mUFC controlled, only mUFC controlled, only LNSC controlled, and neither controlled. Results: Of 160 patients included in the analysis, 85.0% had both LNSC and mUFC uncontrolled at baseline. At week 72, 48.6% of patients had both LNSC and mUFC controlled; these patients generally exhibited greater improvements in cardiovascular/metabolic-related parameters than those with only mUFC controlled or both LNSC and mUFC uncontrolled: systolic/diastolic blood pressure, -7.4%/-4.9%, -6.0%/-5.5%, and 2.3%/0.8%, respectively; fasting plasma glucose, -5.0%, -4.8%, and 1.9%; glycated hemoglobin, -5.1%, -4.8%, and -1.3%. Weight, waist circumference, and body mass index improved with control of LNSC and/or mUFC; physical manifestations of hypercortisolism generally improved regardless of LNSC/mUFC control. Patients with both LNSC and mUFC controlled or only mUFC controlled had the greatest improvement from baseline to week 72 in QoL. Conclusion: In osilodrostat-treated patients with Cushing disease, normalization of LNSC and mUFC led to improvements in long-term outcomes, indicating that treatment should aim for normalization of both parameters for optimal patient outcomes. Clinical trial identifiers: NCT02180217 (LINC 3); NCT02697734 (LINC 4).
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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 | 0.004 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".