<scp>BSH</scp> 2023 Oral abstracts book
Bibliographic record
Abstract
The complement C5 inhibitors eculizumab and ravulizumab are the current standards of care in patients with paroxysmal nocturnal haemoglobinuria (PNH), a rare chronic blood disorder.Ravulizumab provides the same clinical benefit as eculizumab in patients with PNH at a longer dosing interval (every 8 weeks [q8w] vs every 2 weeks [q2w]).Approximately 10%-15% of patients with PNH who receive the approved, fixed eculizumab dose (900 mg q2w) experience insufficient inhibition of intravascular haemolysis (IVH), characterised by breakthrough haemolysis (BTH) towards the end of the dosing interval.In such patients, increasing the eculizumab dose can be effective.However, currently there are no recommendations or clinical trial data regarding the impact of switching these patients to ravulizumab.Study 401 (NCT04320602) is an ongoing, phase 4, singlearm, multicentre trial designed to investigate the impact of switching treatment from fixed, high-dose IV eculizumab (1200 mg q2w) to weight-based IV ravulizumab q8w in adult (≥18 years of age; N = 18) patients with PNH.The primary endpoint is the proportion of patients who experience serum free C5-associated BTH (defined as ≥1 new or worsening symptom or sign of IVH with lactate dehydrogenase [LDH] levels ≥2 x upper limit of normal [ULN] and free C5 concentrations ≥0.5 μg/mL).Other endpoints include change in free C5 concentrations and LDH levels over time.This interim analysis describes data up to day 183 of follow-up.Data for 10/18 enrolled patients (55.6%) were available.From baseline to day 183, no instances of free C5-associated BTH were reported, free C5 concentrations remained below 0.5 μg/mL for all patients at all study timepoints, and LDH levels remained ≤1.5 × ULN in all patients.Up to day 183, 7/10 patients (70.0%) reported treatment-emergent adverse events that were mild (n = 3, 30.0%) or moderate (n = 4, 40.0%) in severity.BTH was reported in one patient which was deemed vaccine-related as two vaccinations were administered the day prior to the event.No elevated free C5 level was detected in the earliest available sample (0.11 μg/ mL, collected four days after the event) and the patient continued ravulizumab treatment.Results of this interim analysis showed that in a sample of ten patients with PNH, switching from high-dose IV eculizumab to standard, weight-based IV ravulizumab q8w was well tolerated.Up to day 183, no free C5-associated BTH was reported and the safety profile of ravulizumab was considered comparable to previously published studies.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.009 |
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; both teacher heads agree on what is shown here.
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".