Dataset Information

Eculizumab in secondary atypical haemolytic uraemic syndrome.

ABSTRACT:

Background

Complement dysregulation occurs in thrombotic microangiopathies (TMAs) other than primary atypical haemolytic uraemic syndrome (aHUS). A few of these patients have been reported previously to be successfully treated with eculizumab.

Methods

We identified 29 patients with so-called secondary aHUS who had received eculizumab at 11 Spanish nephrology centres. Primary outcome was TMA resolution, defined by a normalization of platelet count (>150 × 10 9 /L) and haemoglobin, disappearance of all the markers of microangiopathic haemolytic anaemia (MAHA), and improvement of renal function, with a ≥25% reduction of serum creatinine from the onset of eculizumab administration.

Results

Twenty-nine patients with secondary aHUS (15 drug-induced, 8 associated with systemic diseases, 2 with postpartum, 2 with cancer-related, 1 associated with acute humoral rejection and 1 with intestinal lymphangiectasia) were included in this study. The reason to initiate eculizumab treatment was worsening of renal function and persistence of TMA despite treatment of the TMA cause and plasmapheresis. All patients showed severe MAHA and renal function impairment (14 requiring dialysis) prior to eculizumab treatment and 11 presented severe extrarenal manifestations. A rapid resolution of the TMA was observed in 20 patients (68%), 15 of them showing a ≥50% serum creatinine reduction at the last follow-up. Comprehensive genetic and molecular studies in 22 patients identified complement pathogenic variants in only 2 patients. With these two exceptions, eculizumab was discontinued, after a median of 8 weeks of treatment, without the occurrence of aHUS relapses.

Conclusion

Short treatment with eculizumab can result in a rapid improvement of patients with secondary aHUS in whom TMA has persisted and renal function worsened despite treatment of the TMA-inducing condition.

SUBMITTER: Cavero T

PROVIDER: S-EPMC5410989 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.