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Kidney Week

Abstract: TH-PO802

Risk for TMA Recurrence and Renal Outcomes After Eculizumab Discontinuation in aHUS: Results from the Global aHUS Registry

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Ariceta, Gema, Hospital Universitari Vall d' Hebron, Barcelona, Spain
  • Fakhouri, Fadi, Centre Hospitalier Universitaire de Nantes, Nantes, France
  • Sartz, Lisa, Skåne University hospital, Lund, Sweden
  • Miller, Benjamin, Alexion Pharmaceuticals, Inc., Boston, Massachusetts, United States
  • Nikolaou, Vasilis, Parexel, Uxbridge, United Kingdom
  • Cohen, David J., Columbia University, New York, New York, United States
  • Siedlecki, Andrew M., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Ardissino, Gianluigi, Center for HUS Prevention, Control and Management, Milano, Italy
Background

Eculizumab (Ecu) modifies the course of disease in patients (pts) with atypical hemolytic uraemic syndrome (aHUS), but there are limited data to describe thrombotic microangiopathy (TMA) recurrence rates and long-term outcomes after Ecu discontinuation (d/c).

Methods

Pts in the Global aHUS Registry (NCT01522183) who received ≥1 month (mo) of Ecu with evidence of hematologic or renal response prior to d/c and with ≥6 mo of follow-up (f/u) were included. Those on chronic dialysis (≥3 mo) at the time of Ecu d/c were excluded. Classification as pediatric (<18 years) or adult was made at time of Ecu d/c.

Results

151 pts (62% female) were included in the analysis: 34% were pediatric and 66% were adults (median [range] age at enrolment, 6.0 [0.6–17.1] and 35.7 [18.4–81.2], respectively), 11% had a family history of aHUS and 41% had a pathogenic variant or anti-CFH antibody. Median (range) duration of Ecu prior to d/c was 1.0 (0.1–5.1) and f/u was 2.3 (0.1–7.1) years. 24% experienced TMA recurrence after Ecu d/c. More pts required antihypertensives at f/u vs at d/c (71% vs 54%). Pts with a family history of aHUS, pathogenic variants, lower eGFR and extrarenal manifestations appeared to be at a higher risk of TMA recurrence (Table).

Conclusion

Discontinuation of Ecu is not without risk and may lead to TMA recurrence in some patients with aHUS. A careful assessment of risk factors prior to the decision to d/c Ecu is warranted.

Patient characteristics by TMA recurrence status
VariableAll
N=148*
TMA recurrence
n=35
No TMA recurrence
n=113
Median (range) duration of Ecu before discontinuation, years1.0 (0.1– 5.1)1.0 (0.1– 5.1)1.0 (0.1– 4.5)
Median (range) eGFR prior to Ecu discontinuation, mL/min/ 1.73 m257.1 (4.9–183.1)50.5 (13.0–183.1)65.8 (4.9–176)
Median (range) time to TMA recurrence after Ecu discontinuation, monthsN/AAll: 5.3 (0.1–49.9)
Pediatric: 5.1 (1.4–49.9)
Adult: 10.2 (0.1–49.6)
N/A
Extra-renal manifestation at baseline, n (%)CV 31 (21)
Pulm 19 (13)
CNS 36 (24)
GI 55 (37)
CV 10 (29)
Pulm 9 (26)
CNS 10 (29)
GI 14 (40)
CV 21 (19)
Pulm 10 (9)
CNS 26 (23)
GI 41 (36)
Pathogenic variant, n (%)49 (33)16 (46)33 (29)
Anti-CFH antibody tested and positive, n (%)19 (13)2 (6)17 (15)
Family history, n (%)16 (11)9 (26)7 (6)
eGFR by age category, mL/min/1.73 m2, median (range)
Time pointAll
N=148
Pediatric
n=51
Adult
n=97
Baseline20.7 (3.5–183.1)33.8 (3.9–183.1)18.1 (3.5–156.8)
Discontinuation74.7 (3.6–144.0)93.4 (6.6–144.0)56.0 (3.6–132.3)
Last available follow-up70.2 (3.8–176.0)83.0 (6.1–176.0)61.4 (3.8–131.0)

*TMA recurrence status missing for n=3. Baseline was defined as period prior to first dose of Ecu. CV, cardiovascular; pulm, pulmonary; CNS, central nervous system; GI, gastrointestinal