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Eculizumab prevents thrombotic microangiopathy in patients with atypical haemolytic uraemic syndrome in a long-term observational study.

ABSTRACT: Background:Eculizumab, a terminal complement inhibitor, is approved for atypical haemolytic uraemic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA). Methods:In five parent studies, eculizumab effectively prevented TMA and improved renal and haematologic outcomes in patients with aHUS; therefore, these patients could enrol in this long-term, prospective, observational and multicentre study. The primary endpoint was the TMA manifestation rate off and on eculizumab post-parent study. Post hoc analyses evaluated rates during labelled versus non-labelled dosing regimens, and in those with versus without identified complement abnormalities. Serious targeted treatment-emergent adverse events (TEAEs) were evaluated. Results:Of 87 patients in the current study, 39 and 76 had off- and on-treatment periods, respectively; 17 (44%) with off periods reinitiated eculizumab. TMA manifestation rate per 100 patient-years was 19.9 off and 7.3 on treatment [hazard ratio (HR), 4.7; P?=?0.0008]; rates were highest off treatment and lowest during labelled regimens. TMA manifestations with hospitalizations/serious AEs occurred more frequently off versus on treatment. TMA rates were higher among patients with identified complement abnormalities (HR, 4.5; P?=?0.0082). Serious targeted TEAEs occurred at similar rates off and on treatment. Conclusions:As expected, patients with aHUS have increased risk of TMA manifestations after discontinuation of eculizumab or in the setting of non-labelled eculizumab dosing. Collectively, results show that maintaining eculizumab treatment minimizes risk of TMA, particularly in patients with identified complement abnormalities. Future studies are needed to further characterize TMA and longer term outcomes on labelled or non-labelled eculizumab regimens and after discontinuation of treatment.

SUBMITTER: Menne J

PROVIDER: S-EPMC6452204 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Eculizumab prevents thrombotic microangiopathy in patients with atypical haemolytic uraemic syndrome in a long-term observational study.

Menne Jan J Delmas Yahsou Y Fakhouri Fadi F Fakhouri Fadi F Kincaid John F JF Licht Christoph C Minetti Enrico E EE Mix Chris C Provôt François F Rondeau Eric E Sheerin Neil S NS Wang Jimmy J Weekers Laurent E LE Greenbaum Larry A LA

Clinical kidney journal 20180516 2

<h4>Background</h4>Eculizumab, a terminal complement inhibitor, is approved for atypical haemolytic uraemic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA).<h4>Methods</h4>In five parent studies, eculizumab effectively prevented TMA and improved renal and haematologic outcomes in patients with aHUS; therefore, these patients could enrol in this long-term, prospective, observational and multicentre study. The primary endpoint was the TMA manifestation rate off and ...[more]

PMID: 30976396

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Project description:BackgroundAtypical haemolytic uraemic syndrome (aHUS) is a rare, potentially life-threatening condition caused by dysregulation of the complement pathway. Eculizumab is currently the only approved treatment for this disorder.ObjectiveOur objective was to investigate the impact of early administration of eculizumab on inpatient resource use and hospitalisation costs in 222 patients with aHUS.MethodsWe conducted a retrospective analysis of the Premier Perspective® Hospital Database, including patients with a diagnosis of aHUS and evidence of eculizumab use for aHUS. Early initiation was defined as having received eculizumab within 7 days of admission, with late initiation defined as starting eculizumab on day 8 or later. This date represents the average time required to obtain a specific diagnostic test to discriminate aHUS from a similar haemolytic syndrome that requires a different treatment. Outcome measures were time from first eculizumab initiation to discharge, discharge status or death, days spent in the intensive care unit (ICU), readmission indicators, dialysis indicators, and total hospital costs. Time from first eculizumab initiation to discharge was analysed using a generalised linear model with a log link and an assumed underlying negative binomial distribution. Logistic regression models were used to test the statistical significance of early versus late initiation as a predictor of the occurrence of readmissions, dialysis, and death. Total hospital costs were analysed using a generalised linear model with a log link and an assumed underlying gamma distribution.ResultsBefore modelling, total length of stay and ICU duration were significantly longer for late initiators than for early initiators, and significantly more late initiators were readmitted within 90 days. Late initiation was associated with significantly higher hospital costs than early initiation. After multivariable analysis, late initiators were 3.2 times more likely to require dialysis. However, there was no significant association between early initiation and time to discharge, readmission, or death for any definition or early initiation after multivariable analysis. Estimated total hospital costs (year 2017 values) were $US103,557 in late initiators and $US85,776 in early initiators (p = 0.0024).ConclusionInitiation of eculizumab within 7 days of hospitalisation is associated with lower dialysis rates, less time in ICU, less plasmapheresis, and lower hospitalisation costs compared with late initiation.

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Eculizumab prevents thrombotic microangiopathy in patients with atypical haemolytic uraemic syndrome in a long-term observational study.

Publications

Eculizumab prevents thrombotic microangiopathy in patients with atypical haemolytic uraemic syndrome in a long-term observational study.

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