ESPN 51th Annual Meeting

ESPN 2018


 
Report of 7 cases of eculizumab discontinuation in children with aHUS
ALEXANDRA MAZO 1 PETR ANANIN 2 TATIANA VASHURINA 2 ALEXANDER PUSHKOV 2 KIRILL SAVOSTIANOV 2 ALEXEY TSYGIN 2

1- NATIONAL MEDICAL RESEARCH CENTER OF CHILDRENS HEALTH, Moscow, Russia (AT THE TIME OF THIS RESEARCH)
2- NATIONAL MEDICAL RESEARCH CENTER OF CHILDRENS HEALTH, Moscow, Russia
 
Introduction:

Atypical hemolytic uremic syndrome (aHUS) is a rare disease with multiple organ involvement and predominant acute kidney injury. Treatment with Eculizumab is an only pathogenically aimed approach to aHUS. There is no guidelines yet regulating the term of eculizumab use. 39 children with aHUS were treated by Eculizumab under supervision of our institute. We report of results of discontinuing eculizumab treatment in 7 children with aHUS.

 

Material and methods:

Special diagnostic NGS panel to detect nucleotide substitutions in CFH, CFI, CFB, MCP, and THBD genes, MLPA for deletion at CFHR3/R1 locus. A clinical data were considered.

Results:

Eculizumab was discontinued in 7 patients due to different reasons. Two patients with CFH and CFI mutations relapsed and reestablished remission after eculizumab restart. One patient with deletion in CFHR1/CFHR3 and high titer of anti-CFH antibodies was successfully switched to rituximab. Four patients without mutations and complete recovery of renal function discontinued eculizumab after 7-20 months of treatment and stay stable 12-24 months under close observation. 

Patient No. Sex Age at aHUS onset (y) Complement abnormality Eculizumab duration (mo) Duration of eculizumab discontinuation (mo) Reason of discontinuation Relapse eGFR before eculizumab (ml/min/1.73m2) eGFR after eculizumab discontinuation (ml/min/1.73m2) eGFR at last follow up (ml/min/1.73m2)
 1  M  5.5  CFH (c.3148A>T)  20  2 Allergic reaction  Yes  65  65  69
 2  F  2.2  CFI (с.191C>T)  3  6 Unavailable Drug  Yes  8  8  8
 3  F  8.1 Homozygous deletion at CFHR3/R1 locus
 16  12 Stable Remission  No  8  71  80
 4  F  4.2  No  13  12 Stable Remission  No  110  95  97
 5  M  3.2  No  7  24  Stable Remission  No  100  104  101
 6  F 3.9  No  20  12 Stable Remission  No  95  110  120
 7  M  0.8  No  15  6 Stable Remission  No  8  110  112

  

Conclusions:

We propose a long lasting treatment with eculizumab for patients with mutations while in the absence of genetic abnormalities the treatment could be limited with one year if patient restored kidney function and keeps TMA remission. 

Supported by Russian Science Fund, grant №14-15-00994