MP393LONG-TERM SAFETY AND EFFECTIVENESS OF ECULIZUMAB FOR PATIENTS WITH ATYPICAL HAEMOLYTIC URAEMIC SYNDROME: OUTCOMES FROM A PROSPECTIVE OBSERVATIONAL CLINICAL TRIAL
Bibliographic record
Abstract
INTRODUCTION AND AIMS: To describe the risk of thrombotic microangiopathy (TMA) and long-term safety in patients (pts) with atypical haemolytic uraemic syndrome (aHUS) who received ongoing eculizumab (Ecu) treatment and those who discontinued Ecu or received a non-label recommended regimen. METHODS: Pts with aHUS who participated in any of 5 previous Ecu studies (parent study) could enrol in this observational, long-term follow-up study (NCT01522170). Pts were eligible whether or not they continued the approved dosing regimen after parent study completion. The primary endpoint was TMA rate for ON-treatment (i.e., receiving Ecu regardless of dosing regimen) and OFF-treatment (i.e., discontinued from Ecu) periods. Pts could have both ON and OFF periods. Time to first TMA was analysed using a Cox proportional hazards models with treatment status as a time-dependent explanatory variable. Data cut-off was March 2016. A post-hoc analysis evaluated TMA rate excluding TMAs based on a single laboratory criteria (defined in Table 2). Serious adverse events were also assessed. RESULTS: Clinical and demographic data of 54 adults and 39 children with a median follow-up of 61.5 months (>5 years) are presented in Table 1. Compared to ON-treatment, pts had a 2.8 fold higher TMA rate during OFF-periods (HR=3.4, p=0.001, Table 2). TMA during ON periods was less frequently associated with hospitalisation than OFF periods (4/21 TMAs [19%] vs 15/21 TMAs [71%], respectively). Exclusion of TMAs that only met a single laboratory criterion increased the difference in rate to 6.5 fold (Table 2). Within the ON-treatment group, pts on a non-label recommended regimen had higher TMA rates than patients receiving approved dosing (12.8 vs 6.1/100 pt years). Three pts died (1 ON-treatment, 1 OFF-treatment and 1 on non-approved dosing). No death was considered related to Ecu. Three pts experienced Meningococcal infection (all ON-treatment). All patients recovered and continued on Ecu. MP393 Table 1. Clinical and demographic data MP393 Table 2. Rate of TMA manifestations CONCLUSIONS: This is the largest prospective study of patients with aHUS receiving Ecu to date. Pts with aHUS are at greater risk of TMA when Ecu is discontinued or not administered at the recommended regimen. Ecu continues to be effective and well tolerated after >5 years of treatment. No unexpected safety events were reported.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| 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".