Cyclophosphamide and rituximab in frequently

relapsing/steroid-dependent nephrotic syndrome

Hazel Webb, Graciana Jaureguiberry, Stephanie Dufek, Kjell Tullus, Detlef Bockenhauer

dr. Ruswandiani

 Idiopathic Nephrotic Syndrome is a rare

disease in childhood, incidence 16:
100000

Introductio
n

Steroid sensitive nephrotic syndrome

(SSNS) : response of the disease to
glucocorticoids: prednisolone
Etiology : idipoathic, immune- mediated,
infections
Single episode or chronic relapsing course
with consuquent toxicity from repeated or
ongoing use of glucocorticoid : obesity,
striae distensae, stunted growth,
behavioral abnormalities, osteoporosis

 NS resolves spontaneously
< 10% patients ongoing relapse
Frequent relaps/ steroid depedent NS
( FRSDNS)
To minimize side effect other
immunosuppresive drugs / steroid sparing
medications : cyclosphosphamide,
myocophenolate mofetil, calcineurin
inhibitors
Rituximab is increasingly used in FRSDNS
minimize the use of steroid and other
immunosuppresive drugs

 Retrospective
Medical Record
Great Ormod Street Hosipital for Children
(GOSH), London
December 2006 April 2014

Methods

Case : FRSDNS use rituximab

Control: FRSDNS use cyclophosphamide
Time to first relapse after treatment, side
effects, and other immunosuppresive
medications used
Relapse 3 days of 3+ on dipstick for
protein, plus presence of edema and/or
hypoalbuminemia (<25 g/l)

MannWhitney U test

Results &
Discussion

Baseline
Data
Patient

Median time to relapse : cyclophosphamide : 7 months,

Rituximab 14 months

Long-term remission (>24 months) at least 2 years of

follow-up after treatment :
cyclophosphamide 24% , rituximab 32 %

Other Immunosuppresive medications at

commencement of CPA or rituximab
treatment
Cyclophosphamide

Rituximab
35 CPA before

2 CNI
40 1st
steroid sparing
medication
Prednisone 0.4
mg/kg/day

14 prednisone
only

42

79

37 Levamisole

18 CNI +
prednisone
8 MMF +
prednisone
2 CNI+ MMF +
prednisone

Prednisone 0.3
mg/kg/day

Immunosuppresive medications at first

relapse after of CPA or rituximab treatment

Cyclophosphamide
67 children ( 84%) weaned off prednisolone, median time :
3 months
12 children ( 16%) relapse while still on prednisolone
Median time until 1st relapse : 3 months

Rituximab

36 children (86%) tappering off prednisolone 3 months

6 children (14%) relapse while still on prednisolone
Median time until 1st relapse : 12 months

Side
Effects

3 patients with cyclosphosphamide

neutropenia adjust dose and/or
premature stop of the drug
1 patients bladder obstruction from a
clot from hemorrhagic cystitis
cystoscopy
Patients with rituximab no side effect

median
time to
relapse
(n=34) was
16 months
(range,173months),

Median time
to relapse:
5 months
(range, 1
36 months)
which was

significantly different (p=0.03)

Rituximab 750 mg/m2

single dose

Rituximab
+
cyclophos
phamide

Rituximab 750 mg/m2 in 2

doses

Median time to relapse in children with a

previous cyclophosphamide course
(n=34) and without ( n=8) 9 : 16months
(p=0.305)

Discussion

 Rituximab plays an important role in the

treatment of FRSDNS with a median time
to relapse of 14 months compared to 7
months after cyclophosphamide
Similar to that in other recent reports in
children with FRSDNS of 618months .
No current guidelines about optimal
dosage
Few recent trials FRSDNS, single
injection of 375 mg/m2 good effect

 Rituximab >> cyclophosphamide

Conclusion

Time to first relapse 2x longer and time

off steroid post treatment 4x longer after
rituximab
Rituximab +++ in the most difficult to
treat patients, that is those who received
both cyclosphosphamide and rituximab

 Some of this apparent superior effect

more intensive immunosuppression
received concomitantly.
Children receiving cyclophosphamide
were only receiving prednisolone as
additional immunosuppression
The majority of patients (67 %) receiving
rituximab received at leas one additional
immunosuppressant besides
prednisolone, that is a CNI and/or MMF

Advice

Whether rituximab should continue to be

reserved only for the most difficult to
treat patients or could be a first time
steroid sparing agent in patients FRSDNS
RCT need in the future