Eculizumab (ECU) Significantly Improves Health-Related Quality of Life (HRQoL) in Patients with Atypical Hemolytic Uremic Syndrome (aHUS)
Bibliographic record
Abstract
Abstract Abstract 4772 Background aHUS is a rare, genetic, life-threatening, disease caused by chronic uncontrolled complement activation, which leads to systemic thrombotic microangiopathy (TMA). Despite plasma exchange/infusion (PE/PI), >50% of patients (pts) will either die, require kidney dialysis or have permanent renal damage within the first year of diagnosis. In addition to causing progressive organ damage, the uncontrolled complement activation and subsequent TMA might be expected to impact HRQoL. In 2 prospective, controlled, single-arm phase II trials of aHUS pts receiving ECU, a terminal complement inhibitor, TMA was stopped, there was no longer a need for PE/PI or new dialysis. In one of the trials (C08-002), dramatically, 4/5 pts on dialysis permanently discontinued dialysis as of most recent follow-up. The current analysis evaluates the impact of ECU on HRQoL in aHUS pts. Methods In trial C08-002, 17 pts with aHUS resistant to PE/PI (persistent TMA despite ≥4 PE/PI sessions 1 wk before screening) received ECU. In trial C08-003, 20 pts previously received chronic PE/PI (≥1 every 2 wks and <3 per wk for ≥8 wks prior to ECU). Clinical data, including pt-reported outcomes, were collected at baseline and through the 26-wk treatment and ongoing extension studies up to data cut-off (mean [SD] duration of ECU treatment: C08-002=58 [29] wks and C08-003=60 [12] wks). HRQoL was measured with the EQ-5D self-reporting questionnaire and a 20-cm visual analogue scale (VAS) validated for a number of disease populations. EQ-5D has 5 dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) and 3 levels (no problem, some problems and extreme problems). Change in HRQoL was calculated using the US time trade-off (TTO) index and VAS valuation techniques, and ANOVA analysis. A change of >0.06 is considered a clinically meaningful change Results C08-002: 15/17 pts received ECU until Wk 26 (2 discontinued at Wks 1 and 6; protocol violation and an adverse event unrelated to ECU, respectively) and 13 continued into the extension study. Median age=28 yrs and 29% were on dialysis immediately prior to ECU. Median time from diagnosis to screening =10 mo. All patients had eGFR ≤60 mL/min/1.73m2. C08-003: 20 pts received ECU for 26 wks and 19 continued into the extension study. Median age=28 yrs. Median time from diagnosis to screening=48 mo. Median duration of eGFR ≤60 mL/min/1.73m2=180 days at baseline. HRQoL: In both cohorts of distinct trial pts, ECU substantially improved HRQoL through Wk 26, and sustained this thereafter during long-term ECU therapy (table). In trial C08-002, improvements were seen as early as Day 7 (0.12, p=0.0346). Point estimate improvement (95%CI) in HRQoL from baseline to1 yr was 0.32 (0.27-0.36) for C08-002 and 0.09 (0.05-0.14) for C08-003. On an individual pt basis, 87% and 73% of C08-002 and C08-003 pts, respectively, achieved a clinically meaningful change that represented a clinically important large or moderate improvement in HRQoL measures, respectively. Conclusions aHUS pts have an impaired HRQoL both from a direct impact of aHUS morbidity and management requirements (such as PE/PI), but also from the systemic nature of the disease. In patients with aHUS, significant improvements in HRQoL were achieved rapidly with ECU (as early as Day 7). Sustained long-term treatment with ECU maintained the improvements in HRQoL. Disclosures: Muus: Alexion: Honoraria, Research Funding. Off Label Use: The research described is a clinical trial of eculizumab in patients with aHUS, an indication in which its use is not approved. Licht:Alexion: Honoraria, Research Funding. Goodship:Alexion: Honoraria, Research Funding. Greenbaum:Alexion: Honoraria, Research Funding. Bedrosian:Alexion: Employment. Loirat:Alexion: Honoraria, Research Funding. Legendre:Alexion: Honoraria, Research Funding.
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".