Abstract: FR-OR017
Thrombotic Microangiopathy Frequency in Patients with Atypical HUS: Discontinuing vs Remaining on Eculizumab Treatment
Session Information
- AKI: Can We Improve Outcomes?
October 26, 2018 | Location: 6A, San Diego Convention Center
Abstract Time: 05:42 PM - 05:54 PM
Category: Acute Kidney Injury
- 102 AKI: Clinical, Outcomes, and Trials
Authors
- Ariceta, Gema, Hospital Universitari Vall d' Hebron, Barcelona, Spain
- Ardissino, Gianluigi, Center for HUS Prevention, Control and Management, Milano, Italy
- Sartz, Lisa, Skåne University hospital, Lund, Sweden
- Fakhouri, Fadi, Centre Hospitalier Universitaire de Nantes, Nantes, France
- Gasteyger, Christoph, Alexion Pharma GmbH, Zurich, Switzerland
- Al-Dakkak, Imad, Alexion, Lexington, Massachusetts, United States
Background
Atypical hemolytic uremic syndrome (aHUS) is characterized by thrombotic microangiopathy (TMA). Eculizumab (Ecu), a C5 inhibitor, is the first approved treatment for patients (pts) with aHUS. Using data from the Global aHUS Registry, the largest database of patients with aHUS, we report TMA rate in pts receiving ongoing Ecu vs those who discontinued Ecu.
Methods
Pts enrolled in the non-interventional Global aHUS Registry (NCT01522183) up to 1 January, 2018 were included in this study of real-world data. Pts with unknown treatment status were excluded from this analysis. Additionally, pts with a cobalamin deficiency or diacyl glycerol kinase-ε mutation were excluded from the Ecu treated group. Data were stratified according to Ecu treatment status and descriptive statistics on TMA rate were calculated.
Results
Of the 1475 pts eligible for this analysis, 532 pts were never treated with Ecu and 943 pts were treated with Ecu. Among the latter, 682 pts remained on Ecu without discontinuing treatment, 218 pts discontinued Ecu without restarting and 43 pts discontinued and restarted Ecu. Overall, pts who remained on Ecu had a lower TMA rate than pts who were never treated and pts who discontinued treatment (3.6, 27.5 and 10.7 per 100 pt-years, respectively; Table).
Conclusion
In this, the largest cohort ever analyzed in a real-world, non-randomized setting to address the question of treatment maintenance in aHUS, pts who continued to receive Ecu had a substantially lower risk of TMA than those who discontinued or never received Ecu.
Clinical characteristics per eculizumab treatment status
| Never treateda | Discontinued never restartedb | Discontinued and restartedc | Ongoing treatmentd | ||
| n | 532 | 218 | 43 | 682 | |
| TMAs | Pts with TMA (events) | 171 (301) | 6 (7) | 7 (10) | 68 (120) |
| TMA rate/100 pt-years | 27.5 | 10.7 | 23.9 | 3.6 | |
| Time on Ecu (years) | Median (IQR) | – | 0.6 (0.1–1.2) | 2.7 (0.8–3.8) | 1.6 (0.5–3.5) |
| Time to restart Ecu (years) | Median (IQR) | – | – | 0.4 (0.1–1.5) | – |
| Follow-up time (years) | Median (IQR) | 1.9 (1.0–3.3) | 2.3 (1.2–3.2) | 3.0 (2.0–3.9) | 2.0 (1.0–3.1) |
| aPts who were never treated with Ecu (TMAs evaluated from enrollment to last follow up); bPts who discontinued Ecu and never restarted (TMAs evaluated from discontinuation to last follow up); cPts who discontinued Ecu and restarted (TMAs evaluated from first discontinuation to first restart); dPts who never discontinued Ecu (TMAs evaluated from treatment start to last follow up). The definition of TMA was as evaluated by investigator. Decision to treat or discontinue with Ecu was not randomized but made by the investigator. Ecu, eculizumab; IQR, interquartile range; n, total number in group; pts, patients; TMA, thrombotic microangiopathy. | |||||
Funding
- Commercial Support – Alexion Pharmaceuticals