Sindrome hemolitico uremico atipico

1. Congreso Nacional de Nefrología
Actualidades en el tratamiento de SHUa
Dr. Juan Antonio Flores Jiménez
Hematólogo-Medicina Interna-Trasplantes
Hospital de Especialidades Puerta de Hierro
Guadalajara, Jal.
Guadalajara, Jal. septiembre de 2021.

2. Conflictos de interés
• Speaker para Asofarma, Janssen, Novartis, MSD, Astra Zeneca,
Alexion, CSL Berhing
• Advisor para Asofarma, MSD.

5. Tratamientos disponibles
Plasmaféresis
Eculizumab
Combinación de trasplante riñon o riñon-hígado
Soporte
PG, plaquetas, líquidos IV, evitar nefróxicos, inicio de tto sustitutivo, nutrición.

6. Eculizumab: primer anticuerpo Anti-C5 humanizado
IgG, inmunoglobulina G
Rother et al. Nat Biotechnol 2007;25:1256–1264
Bisagra
CH3
CH2
IgG4 cadena pesada
Regiones constantes 2 y 3
(elimina activación de complemento)
Complementariedad de las regiones determinantes
(origen murino)
Marco de regiones humanas
 No mutaciones
 Línea germinal
IgG2 cadena pesada
region constante 1 y bisagra
(elimina el receptor anclaje Fc)

7. C5
Proximal
Terminal
Figueroa JE, Densen P. Clin Microbiol Rev. 1991;4(3):359-395. Walport MJ. N Engl J Med. 2001;344(14):1058-66. Rother RP et al. Nature Biotech. 2007;25(11):1256-64.
C5a
Eculizumab
 Las funciones proximales del
complemento permancen
intactas
– Anafilotoxina débil
– Aclaramiento de inmunocomplejos
– Opsonización de microorganismos
 El complejo terminal de ataque a la
membrana queda bloqueado C5b-9
 Alta afinidad por C5
Cascada
C5b-9
C5b
C3 C3a
C3b
Eculizumab bloquea el Complemento Terminal

8. Eculizumab
Brodsky, Blood Rev 2008
Eculizumab se une
específicamente a C5 y
bloquea su union a C5a y C5b
Activación del complemento terminal es
bloqueada
 Riesgo incrementado para infecciones por meningococo (0.5/año/100 pacientes)
 Uso obligatorio de la vacuna tetravalente conjugada para meningococo.
 ± Profilaxis antimicrobiana continua
 Es importante brindar información paciente y familia, tarjeta de información

9. Eculizumab Multinacional, Multi-Center Clinical Program in (N=67)
Study C09-001
(N=30)
19 Patients <18 years old
Clinical Diagnosis
of aHUS1:
Medical Practice
Setting
Clinical Diagnosis of aHUS With1:
 TMA (measured by platelet count, hemolysis)
 Organ Damage (serum creatinine ≥ULN)
 ADAMTS13 >5%; no positive STEC test
 No requirement for identified genetic mutation
Retrospective1
Prospective1
Long-term Extension Studies 2,3
86% (32/37) of patients continued chronic
eculizumab treatment in extension studies
Study C08-003
(N=20)
Adult/Adolescent
Study C08-002
(N=17)
Adult/Adolescent
(26 weeks)
Licht C et al. ASN Annual Meeting 2011 (Poster TH-PO366).
Greenbaum L et al. ASN Annual Meeting 2011 (Poster TH-PO367).

10. Prospective Studies: Eculizumab Dosing Schedule*
Pretreatment Induction Phase Maintenance Phase
2 weeks
before induction
Week
→
1 2 3 4 5 6 7 8
9 and
every
2 weeks
thereafter
Neisseria
meningitidis
vaccination/
antibiotics
Eculizumab
dose, mg
→
900 900 900 900 1200 X 1200 X 1200
 Administration: IV infusion over 35 min every 7 d during induction and every 14 d during maintenance
– Dose adjustment to every 12 days permitted
 Meningococcal prophylaxis: patients received meningococcal vaccination prior to receipt of eculizumab or received
prophylactic treatment with antibiotics until 2 weeks after vaccination
 Severe TMA complications observed in aHUS patients deviating from recommended dosing schedule
− 5/18 patients experienced TMA complications following missed dose
− Eculizumab was reinitiated in 4/5 patients
*For patients <18 years of age, administration of eculizumab is based on body weight.
Soliris® (eculizumab). Prescribing information. Alexion Pharmaceuticals, Inc. 2011.

11. Eculizumab – Approved Dosing Schedule in aHUS
For patients 18 years of age, eculizumab therapy consists of:
Patient Body Weight Induction Maintenance
40 kg and over 900 mg weekly x 4 doses
1200 mg at week 5;
then 1200 mg every 2 weeks
30 kg to less than 40 kg 600 mg weekly x 2 doses
900 mg at week 3;
then 900 mg every 2 weeks
20 kg to less than 30 kg 600 mg weekly x 2 doses
600 mg at week 3;
then 600 mg every 2 weeks
10 kg less than 20 kg 600 mg weekly x 1 dose
300 mg at week 2;
then 300 mg every 2 weeks
5 kg to less than 10 kg 300 mg weekly x 1 dose
300 mg at week 2;
then 300 mg every 3 weeks
Induction Maintenance
900 mg weekly x 4 doses
1200 mg at week 5;
then 1200 mg every 2 weeks
For patients <18 years of age, administer eculizumab based upon body weight,
according to the following schedule:
Prescribing information. Alexion Pharmaceuticals, Inc. 2011.

12. Soliris [prescribing information]. Boston, MA: Alexion Pharmaceuticals; 2019.
SELECT IMPORTANT SAFETY INFORMATION
12
WARNING: SERIOUS MENINGOCOCCAL INFECTIONS
Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris® (eculizumab). Meningococcal infection may
become rapidly life-threatening or fatal if not recognized and treated early.
• Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients
with complement deficiencies.
• Immunize patients with meningococcal vaccines at least 2 weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris
therapy outweigh the risk of developing a meningococcal infection. (See Serious Meningococcal Infections for additional guidance on the
management of the risk of meningococcal infection)
• Vaccination reduces, but does not eliminate, the risk of meningococcal infections. Monitor patients for early signs of meningococcal infections
and evaluate immediately if infection is suspected.
Soliris is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the Soliris REMS, prescribers
must enroll in the program. Enrollment in the Soliris REMS program and additional information are available by telephone: 1-888-SOLIRIS (1-888-
765-4747) or at www.solirisrems.com.

13. Recomendaciones de tratamiento: Consenso Español
Los autores del documento recomiendan su uso precoz tanto en pacientes con
sospecha clínica de SHUa en riñones nativos como en pacientes con recurrencia del
SHUa tras el TR.
Actualización en síndrome hemolítico urémico atípico: diagnóstico y tratamiento. Documento de consenso. Campistol JM, Arias M, Ariceta G, Blasco M,
Espinosa M, Grinyó JM, Praga M, Torra R, Vilalta R, Rodríguez de Córdoba S. Nefrologia 2015;35(5):421–447

14. TMA Event-Free Status Achieved and Maintained
Through 2 Years with Ongoing Eculizumab
• No decrease in platelet count
>25% from baseline AND
• No plasma exchange/infusion
AND
• No new dialysis
For at least 12 consecutive week
• In 20/20 patients:
• Elimination of PE/PI AND
• No new dialysis
• The benefit was sustained
through the entire study
period (median eculizumab 62
weeks)
Median of
62 Weeks
Treatment
Week 26
80%
(56-94)
85%
(62-97)
Primary
endpoint
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Patients
Achieving
TMA-Event–Free
Status
16/20 17/20 19/20
95%
(75-100)
2 Years
Goodship T et al. Presented at ASN; November 1, 2012; San Diego, CA. Poster TH-PO442

15. Number of
patients
Figure 1. Mean (SE) Changes from Baseline to
Week 52 in (a) Platelet Count
17
 Mean platelet
increase between
baseline and 52
weeks: 90 x109/L
(p<0.0001)
 Significant
increase in
platelet count as
early as Day 7
(p=0.027)
 Platelet increase
sustained through
a median duration
of 64 weeks
Chronic Eculizumab Inhibited
Complement-Mediated TMA as Measured
by a Significant Increase in Platelet Count
0
20
40
60
80
100
120
140
0 28 56 84 112 140 168 196 224 252 280 308 336 364
Least-squares
Mean
(95%CI)
Change
in
Platelet
Count
(10
9
/L)
from
Baseline
Days
16 15 14 15 15 14 6 13 13 13 12 11 12
†
†
*p≤0.01
†p<0.05
†
* * * * * * * * * * * * * * * * *
Complement-mediated TMA
C08-002
Greenbaum L et al. ASH Annual Meeting 2011 (Oral Presentation 193).

16. Eculizumab eliminó la diálisis en 4/5 pacientes
(n=5)
One patient developed a new dialysis requirement during eculizumab treatment; this patient discontinued eculizumab due to an
adverse event unrelated to eculizumab treatment (worsening of pancytopenia).
Patients eliminated dialysis within 14 days following initiation of eculizumab.
Permanecieron libres de diálisis
hasta por 64 semanas
Greenbaum L et al. ASN Annual Meeting 2011 (Poster TH-PO367).
%
pacientes
libres
de
diálisis

17. Earlier Intervention With Eculizumab Leads to Greater Improvement in
Renal Function
60
36
23
7
-10
10
30
50
70
0.26-0.3 0.3-1.0 1.0-2.0 2.0-4.0
Mean
Change
in
eGFR
Through
Median
Duration
of
64
Weeks
(mL/min/1.73m2)
Duration from Current Clinical Manifestation of TMA to Screening
(months)
n=4 n=4 n=4 n=3
 Week 52 (repeated measures model with clinical disease manifestation as covariate, p =
0.03)
Median duration of aHUS current clinical manifestation to study was 0.75 months (range, 0.2–4.0).
Greenbaum L et al. ASH Annual Meeting 2011 (Oral Presentation 193).

18. Earlier Intervention With Eculizumab Leads to Greater Improvement in
Renal Function
n=4 n=4 n=4 n=3
Pooled analysis from four phase 2, open-label, single-arm, prospective clinical studies of eculizumab for
patients with aHUS. N=97
Vande Walle et al., 2016

19. Earlier Intervention With Eculizumab Leads to Greater Improvement in Renal Function
n=4 n=4 n=4 n=3
Pooled analysis from four phase 2, open-label, single-arm, prospective clinical studies of eculizumab for
patients with aHUS. N=97
Vande Walle et al., 2016

20. Soliris [prescribing information]. Boston, MA: Alexion Pharmaceuticals; 2019.
Patient Counseling
Advise the patient to read FDA-Approved Patient Labeling (Medication Guide)
Signs and Symptoms of Meningococcal Infection
• Inform patients about any of the signs and symptoms of meningococcal infection and strongly advise patients to seek immediate medical attention if these
occur. These signs and symptoms are:
• Headache with nausea or vomiting
• Headache and a fever
• Headache with a stiff neck or stiff back
• Fever
• Fever and a rash
• Confusion
• Muscle aches with flu-like symptoms
• Eyes sensitive to light
• Inform patients that they will be given a Soliris® (eculizumab) Patient Safety Information Card that they should carry with them at all times. This card
describes symptoms which, if experienced, should prompt the patient to immediately seek medical evaluation.
20

21. Soliris [prescribing information]. Boston, MA: Alexion Pharmaceuticals; 2019.
Patient Counseling
Other Infections
• Counsel patients about gonorrhea prevention and advise regular testing for patients at-risk.
• Inform patients that there may be an increased risk of other types of infections, particularly those due to encapsulated bacteria.
Aspergillus infections have occurred in immunocompromised and neutropenic patients.
Inform parents or caregivers of children receiving Soliris® (eculizumab) for the treatment of aHUS that their child should be vaccinated against
Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) according to current medical guidelines.
Discontinuation
• Inform patients with aHUS that they there is a potential for TMA complications due to aHUS when Soliris is discontinued and they will be monitored by their
healthcare professional for at least 12 weeks following Soliris discontinuation.
• Inform patients who discontinue Soliris to keep the Soliris Patient Safety Information Card with them for three months after the last Soliris dose, because
the increased risk of meningococcal infection persists for several weeks following discontinuation of Soliris.
21

22. What is the efficacy of
eculizumab in patients with
aHUS in terms of Impact on
renal functioN?
Table of Contents
Important Safety
Information
M/GL/SOL-a/0001

23. CKD Stage At 26 weeks in Patients With aHUS on Eculizumab1,a
23
aAt week 26, data was not available for 12/41 (29%) patients.1
CKD, chronic kidney disease.
1. Fakhouri F, et al. Am J Kidney Dis. 2016;68(1)84-93. 2. Fakhouri F, et al. Presented at: American Society of Nephrology Kidney Week 2014
Annual Meeting; November 11-16, 2014; Philadelphia, PA.
5%
15%
35%
5%
12%
29%
0%
21%
33%
4%
17%
25%
12%
6%
36%
6% 6%
35%
0%
5%
10%
15%
20%
25%
30%
35%
40%
Stage 1 Stage 2 Stage 3 Stage 4 Stage 5 Unknown
%
of
patients
CKD Stage
All patients On dialysis on baseline Not on dialysis at baseline
C10-004:
Earlier Diagnosis and
Treatment
63% (26/41) of patients improved by 1 or more stage of CKD at the end of
26 weeks, which increased to 68% (28/41) at the end of 1 year1,2
Table of Contents

24. What is the efficacy of
eculizumab in patients with
aHUS who have underwent
renal transplant?
Table of Contents
M/GL/SOL-a/0001

25. Renal Transplant Is Associated With a High Rate of Graft Loss in
Patients With aHUS
aDiagnosis of TMA post-transplant was assessed by histological criteria, including arterial and glomerular lesions.
TMA, thrombotic microangiopathy.
Le Quintrec M, et al. Am J Transplant. 2013;13(3):663-675.
25
Graft survival was significantly lower in patients with than in those without subsequent TMAa
71 51 42 37 25 15 8 3 1
Number at risk
Death-censored
graft
survival
(%)
Time (months)
100
80
60
40
20
0
0 20 40 60 80 100 120 140 160
Death-Censored Graft Survival in 57 Patients With aHUS Who
Received 71 Renal Grafts
51% 5-year graft survival
Used with permission from Le Quintrec M, et
al. Am J Transplant. 2013;13(3):663-675.

26. Secondary end point Results: impact
on kidney transplants in C08-002
and C08-003
26
eGFR, estimated glomerular filtration rate.
1. Licht C, et al. Kidney Int. 2015;87(5):1061-1073. 2. Legendre CM, et al. N Engl J Med. 2013;368(23):2169–2181.
• In C08-002, there was no change in the number of patients who received a kidney transplant between
baseline and the end of the extension study1
• No patients lost existing renal grafts in C08-002 or C08-0031
C08-002:
Progressing TMA
C08-003:
Long Duration of aHUS and
CKD
Early intervention with eculizumab was associated with greater
improvement in eGFR in both trials2

27. What is the efficacy and safety
of eculizumab in patients With
aHUS who have undergone
renal transplant?

28. A Pooled Post Hoc Analysis of Patients With
and Without Renal Transplant
Legendre CM, et al. Transpl Int. 2017;30(12):1275-1283.
28
Patients in this post hoc analysis included those enrolled in the 4 prospective eculizumab
clinical trials (C08-002, C08-003, C10-003, and C10-004)
C08-002
N=17
C08-003
N=20
C10-003
N=22
C10-004
N=41
Post Hoc Analysis
N=100
Native kidney
n=74
Transplanted kidney
n=26

29. Demographic and Baseline Clinical
Characteristics
aP values were calculated using Wilcoxon rank-sum tests for continuous variables and Fisher exact tests for categorical variables between native kidney and transplant subgroups at baseline.
eGFR, estimated glomerular filtration rate; LDH, lactate dehydrogenase; PE/PI, plasma exchange/plasma infusion; TMA, thrombotic microangiopathy; U/L, upper limit.
Legendre CM, et al. Transpl Int. 2017;30(12):1275-1283.
29
Characteristic
All Patients
(N=100)
Native Kidney
(n=74)
Transplanted Kidney
(n=26)
P Value Between
Subgroupsa
Age, median (range), years 28.0 (0-80) 24.0 (0-80) 41.5 (17-69) 0.0002
Female, n (%) 62 (62) 46 (62) 16 (62) 1.0000
Identified complement mutation or autoantibody, n (%) 59 (59) 46 (62) 13 (50) 0.3549
Time from aHUS diagnosis to screening, median (range), months 2.7 (0.03-311.3) 0.85 (0.03-235.9) 34.8 (0.13-311.3) <0.0001
TMA events, median (range), n 1 (1-9) 1 (1-9) 2 (1-8) 0.0005
Duration of current TMA manifestation to first eculizumab dose, median
(range), months
0.72 (0.03-47.4) 0.69 (0.03-47.4) 1.25 (0.03-36.7) 0.4081
First TMA manifestation, n (%) 58 (58) 51 (69) 7 (27) 0.0002
No PE/PI during current manifestation, n (%) 28 (28) 18 (24) 10 (39) 0.2061
Platelet count, median (range), × 109/L 126 (16.9-420.5) 118.5 (18.0-420.5) 139.8 (16.0-337.5) 0.1080
hemoglobin level, median (range), mg/dL 89.5 (41.0-131.0) 85.5 (41.0-131.0) 96.5 (54.0-131.0) 0.0075
LDH level, median (range), U/L 369 (131.0-7164.0) 380.5 (134.0-7164.0) 304.5 (131.0-2693.0) 0.1313
eGFR, median (range), mL/min/1.73 m2 16.0 (5.6-105.5) 12.0 (5.6-105.5) 22.2 (10.0-72.3) 0.1386
Dialysis at baseline, n (%) 43 (43) 37 (50) 6 (23) 0.0214
Patients with transplanted kidneys were older, had a longer time from aHUS diagnosis to screening for a clinical trial, were less likely to be experiencing
their first TMA manifestation, and were less likely to be on dialysis

30. Patients Both With Native and Transplanted
Kidneys Achieved Hematologic Study End points
With Eculizumab Usea
*P values between native kidney and transplant subgroups were calculated using Fisher exact tests.
aEnd points were defined by study protocols. Complete TMA response was defined as platelet count ≥150 × 109/L, LDH<ULN, and ≥25% decrease from baseline in SCr level. TMA
free status was defined as no decrease in platelet count >25% from baseline, no PE/PI, and no new dialysis. Hematologic normalization was defined as a platelet count ≥150 × 109/L
LDH<ULN. Categorical end points were required to be sustained for 2 or more consecutive measurements obtained ≥4 weeks apart.
CI, confidence interval; LDH, lactate dehydrogenase; PE/PI, plasma exchange/plasma infusion; SCr, serum creatinine; TMA, thrombotic microangiopathy; ULN, upper limit of normal.
Legendre CM, et al. Transpl Int. 2017;30(12):1275-1283.
30
End point
All Patients
(N=100)
Native Kidney
(n=74)
Transplanted Kidney
(n=26)
P Value*
Complete TMA response
n (%)
95% CI
72 (72)
62−81
55 (74)
63−84
17 (65)
44−83
0.4486
TMA event-free status
n (%)
95% CI
92 (92)
87−98
69 (93)
87−99
23 (88)
74−99
0.6433
Hematologic normalization
n (%)
95% CI
93 (93)
86−97
71 (96)
89−99
22 (85)
65−96
0.0727

31. Patients with transplanted kidneys required more
time to achieve study end points vs those with
native kidneys
TMA, thrombotic microangiopathy.
Legendre CM, et al. Transpl Int. 2017;30(12):1275-1283.
31
Patients in both groups with platelet counts <150 × 109/L experienced significant improvement by 26 weeks of
eculizumab treatment (P<0.0001 for patients with native kidneys and P=0.006 for patients with transplanted kidneys)
66
98
33
56
66
33
98
56
0 20 40 60 80 100
Time to complete TMA response
Time to hematologic normalisation
Days
Transplanted kidney (n=26) Native kidney (n=74)

32. Patients Both With Native and Transplanted Kidneys Achieved Renal
Study End points With Eculizumab Use
CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; SD, standard deviation.
Legendre CM, et al. Transpl Int. 2017;30(12):1275-1283. Legendre CM, et al. Transpl Int. 2017;30(12):1275-1283.
32
All patients experienced a significant increase in eGFR from baseline to 26 weeks (P<0.0001 for
patients with native kidneys, n=71; and P=0.0092 for patients with transplanted kidneys, n=25)
End point Native Kidney Transplanted Kidney
Absolute eGFR at 26 weeks, mean (SD), mL/min/1.73 m2 61 (41), n=71 37 (25), n=25
eGFR change from baseline at 26 weeks, mean (SD), mL/min/1.73 m2 38 (36), n=71 11 (20), n=25
Absolute eGFR at 18 months, mean (SD), mL/min/1.73 m2 66 (31), n=35 42 (27), n=20
eGFR change from baseline at 18 months, mean (SD), mL/min/1.73 m2 44 (34), n=35 13 (23), n=20
CKD stage improvement by ≥1 stage at 26 weeks, n/N (%) 47/74 (64) 13/26 (50)
CKD stage improvement by ≥1 stage at end of study, n/N (%) 55/74 (74) 15/26 (58)

33. Safety in the Post Hoc Analysis
TEAEs, treatment-emergent adverse events.
Legendre CM, et al. Transpl Int. 2017;30(12):1275-1283.
33
TEAEs were similar in both groups and were mild or moderate in severity
Native Kidneys Transplanted Kidneys
Number of patients experiencing TEAEs 47% (35/74) 53% (14/26)
Most frequently reported TEAEs (occurring in >5% of the
subgroup)
Alopecia, headache, leukopenia, vomiting
BK virus infection, headache, leukopenia,
lymphopenia, pyelonephritis, urinary tract
infection
Most frequently reported severe TEAEs
Dyspnea (1/74), gonococcal genitourinary tract
infection (1/74), influenza (1/74), hypertension
(1/74), peritonitis (1/74), venous thrombosis
(1/74)
Meningococcal meningitis (1/26), pyelonephritis
(2/26), renal impairment (1/26), vein disorder
(1/26)
Development of meningococcal infection 1 patient 1 patient
Deaths None reported
1 patient died due to complications from intestinal
hemorrhage unrelated to eculizumab use
Table of Contents

34. How does Eculizumab Impact
HRQoL in Patients With aHUS?
M/GL/SOL-a/0001

35. Mean EQ-5D Score Over 26 Weeks With
Eculizumab Usea
aA change from baseline of 0.06 is considered clinically meaningful.
eGFR, estimated glomerular filtration rate; FACIT, Functional Assessment of Chronic Illness Therapy; SF-36, 36-Item Short Form Health Survey.
Fakhouri F, et al. Am J Kidney Dis. 2016;68(1)84-93.
35
C10-004:
Earlier Diagnosis and
Treatment
Mean
eGFR
change
from
baseline
(mL/min/1.73
m
2
)
0.35
0.3
0.25
0.2
0.15
-0.35
-0.3
0.05
0
-0.05
-0.1
-0.15
-0.2
-0.25
0.1
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 23 25 26
22 24
n = 32
Eculizumab treatment (weeks)
28 6 7 22 23
†
*
*
Beginning after 1 month of eculizumab treatment, FACIT-
Fatigue scores improved compared with baseline (P=0.005)
Used with permission from Fakhouri F, et al. Am J Kidney Dis. 2016;68(1)84-93.
Table of Contents

36. Are there any additional biomarker studies
evaluating the ability of eculizumab to inhibit
terminal complement in patients with aHUS?

37. Fold Increase in Markers of Proximal Complement Activity
in Patients With aHUS vs Healthy Volunteers
A pre-specified exploratory analysis of biomarkers in patients with aHUS enrolled in
C10-004
BL, baseline; HVs, healthy volunteers.
Cofiell R, et al. Blood. 2015;125(21):3253-3262.
Fold Increase in Markers of Terminal Complement Activity
in Patients With aHUS vs Healthy Volunteers
Plasma Ba sVCAM-1
Median-fold
elevation
compared
with
that
of
HVs
7 -
6 -
5 -
4 -
3 -
2 -
1 -
0 -
Patients with aHUS at BL
HVs
Patients with aHUS on eculizumab
therapy
U-C5a U-sC5b-9
Median-fold
elevation
compared
with
that
of
HVs
400 -
300 -
200 -
40 -
30 -
20 -
1 -
0 -
Patients with aHUS at BL
HVs
Patients with aHUS on eculizumab
therapy
Blockade of terminal complement activation with eculizumab led to reductions in levels of markers of complement activation,
including U-C5a and U-sC5b-9 (P<0.0001 vs baseline by 2.5 weeks and at all later points)