4 - PosterSessionOnline

RITUXIMAB TREATMENT IN RESISTANT PRIMARY
GLOMERULONEPHRITIS: A CROATIAN CLINICAL RETROSPECTIVE STUDY
Mario Laganović 1, Mladen Knotek2 , Krešimir Galešić3, Dario Nakić4, Dubravka Mihaljević 5, Ana Vrdoljak 1, Vanja Ivković 1, Marijana Ćorić 6,
Danica Ljubanović Galešić7, Bojan Jelaković1
1 Department
of Nephrology, Hypertension, Dialysis and Transplantation, University Hospital Center Zagreb, School of Medicine University of Zagreb, Croatia,
2 Department of Nephrology, Clinical Hospital Merkur, School of Medicine University of Zagreb, Croatia
3 Department of Nephrology and Dialysis, Clinical Hospital Dubrava, School of Medicine University of Zagreb, Croatia
4 Department of Nephrology and Dialysis, General Hospital Zadar, Croatia
5 Department of Nephrology, University Hospital Center Osijek, School of Medicine University of Osijek, Croatia,
6 Department for Pathology, University Hospital Centre Zagreb, School of Medicine University of Zagreb, Croatia
7 Department for Pathology, Clinical Hospital Dubrava, School of Medicine University of Zagreb, Croatia
Introduction
Resistant primary glomerulonephritis (rPGN) represents significant clinical problem. Therapeutic resitance to conventional treatment
which includes steroids, alkylating agents , calcineurin inhibitors and micofenolate mofetil have consequence of prolonged exposure to immunosuppressive
therapy, complications of persistant nephrotic syndrome or progression to end stage renal failure. Increased knowledge of pathogenesis of glomerular disease
leads to development of new treatment modalities which provided hope that patients resistant to conventional treatment could be treated with more effective and
better tolerated therapy. B cell targeted therapy is a plausibile treatment option in disease in which B cells and antibodies play a critical role.
Objective: our aim was to investigate effectiveness of rituximab, monoclonal antibody directed against the B-cell antigen CD 20, in this particular group
of patients. We perform the first Croatian multicentre retrospective study to evaluate the clinical course of patients with rPGN treated with rituximab.
Subjects and methods
Results
Baseline patients characteristics and respose o treatment are shown on table
We included 25 patients (15/60% M, 10/40%
F), median age 50 y (22-71) with biopsy proven PGN: 11 membranous
nephropathy (MN), 9 focal segmental glomerulosclerosis (FSGS), 2
minimal change disease (MCD), 2 ANCA associated vasculitis (AAV)
and 1 membranoproliferative glomerulonephritis (MPGN). All patients
were treated previously
with combination of corticosteroids,
cyclophosphamide, cyclosporine and mycophenolate mophetil without
achieving remission. Rituximab was administered either in 2 doses of 1
g 2 weeks apart or 375 mg/m2 in 4 weekly doses. We defined complete
remission as persistent proteinuria < 0.3 g/du and normal serum
creatinine (cCr) and partial remission as persistent proteinuria < 3.5
g/du or decrease > 50% from baseline with stable sCr.
1. During a median follow-up of 10.5 ( 3-48) months after rituximab administration 18
(72%) patients achived complete (6/24%) or partial remission (12/48%), both patients
with MCD and AAV, 81% patients with MN and 44% patients with FSGS. The average
time to remission was 6 (2-16) months. 2 patients progressed to ESRD (1 MN, 1
FSGS). Average time of depletion of CD 20 lymphocyte was 14 (7-30) days (figure1).
Initial sCre was 136 (67-441) µmol/l eGFR 68 (21-127) ml/min/1.73m2 and proteinuria
6.64 (2.4-50) g/dU. Significant reduction was observed in the proteinuria values 2,0
(0.1-13 g/dU (p=0.031). eGFR increased by 7.8 ml/min/1.73m2 (p=0,044). On logistic
regression adjusted for proteinuria and eGFR only length of follow-up was positive
predictor of response to rituximab (OR 1.03 CI 1.00-1.05 p=0.05). No serious, treatment
related side effects were observed.
Table 1. Baseline patients characteristics and response to treatment
Patient Gender
1
F
2
M
3
M
4
F
5
M
6
F
7
F
8
M
9
M
10
M
11
M
12
F
13
F
14
M
15
M
16
M
17
F
18
F
19
M
20
M
21
M
22
M
23
M
24
F
25
F
Age
64
53
27
50
42
30
36
32
37
71
38
55
50
70
41
49
56
35
64
61
69
22
59
58
51
Diagnosis
FSGS
FSGS
FSGS
FSGS
FSGS
FSGS
FSGS
FSGS
FSGS
MN
MN
MN
MN
MN
MN
MN
MN
MN
MN
MN
MCD
MCD
AAV
AAV
MPGN
Disease
duration
(months)
96
144
120
180
36
12
24
48
72
144
24
4
180
180
36
240
51
5
48
48
12
204
12
36
60
Previous
Creatinine
therapy
(µmol/l)
CS+CYP+CSA
304
CS+CYP+CSA
136
CS+CYP+-CSA+MMF
118
CS+CYP+-CSA+MMF
87
CS+CYP+-CSA+MMF
203
CS+CYP+-CSA+MMF
441
CS+CYP
347
CS+CYP+CSA
74
CS+CYP+CSA
87
CS+CYP+CSA
92
CS+CYP+CSA
88
CS+CSA
92
CS+CYP+-CSA+MMF
90
CS+CYP+-CSA+MMF
194
CS+CYP+-CSA+MMF
175
CS+CSA
85
CS+CYP+CSA
204
CS+CSA
89
CS+CYP
99
CS+CYP+CSA
70
CS+CYP+CSA
189
CS+CYP+-CSA+MMF
67
CS+CYP
229
CS+CYP
179
CS
92
eGFR
(ml/min/
1,73 m2)
21
70
85
66,9
54,5
20
13,1
113
91
125
153,6
78,7
80
41
47,8
88,3
27
66,9
70,2
105,7
34
127
27,1
26,8
59,3
Proteinuria
(g/dU)
16,5
5
5
7,9
13,9
50
21,9
10,4
7,6
9
5,8
5,3
7,9
14
4,72
4,25
4,7
2,6
3,5
5,3
9,5
6,8
11
2,8
2,43
Systolic
BP
(mmHg)
120
120
140
150
160
110
135
160
150
140
140
110
125
120
120
130
185
150
130
140
160
110
150
140
130
Diastolic
BP
(mmHg)
80
80
100
80
103
74
88
105
92
80
80
70
76
80
80
80
105
90
80
85
80
70
90
85
80
RTX dosing
regimen
(doses)
2
4
4
4
4
4
4
4
2
2
4
4
4
4
4
4
4
2
2
2
2
2
4
2
2
Dose
(mg)
2000
2000
2000
2800
3200
3600
2800
3600
1000
4000
2800
2000
2800
3600
3600
1400
2000
1000
1000
1000
2000
1600
2000
1500
1000
Follow- Response
up
to
(months) tretment
12
PR
5
PR
5
NR
48
PR
14
NR
12
NR
6
NR
36
NR
3
CR
18
CR
4
NR
16
PR
29
CR
20
PR
4
NR
14
PR
24
CR
7
PR
9
CR
7
PR
7
PR
12
CR
6
PR
17
PR
6
PR
F- female; M- male; FSGS – focal segmental glomerulosclerosis; MN – membranous nephropathy; MCD – minimal change disease; AAV – ANCA associated vasculitis; MPGN – membranoproliferative
glomerulonephritis; CS – corticosteroids; CYP – cyclophosphamide; CSA – cyclosporine; MMF – mycophenolate; CR – complete remission, PR – partial remission, NR – no remission
Figure 1. Cumulative dose of rituximab, CD depletion and time to remission
grams 3000
2500
Conclusion
2555
2254
2000
1800
1750
1500
1000
1000
500
0
FSGS
CD20 deplation
(days)
Time to remission
(months)
MN
MCD
AAV
MPGN
21
15
-
7
14
5.5
6
6
4
3
Rituximab appears to be effective and safe treatment
option for patients with resistant primary glomerulonephritis
particularly for patients having membranous nephropathy,
minimal change disease and ANCA associated vasculitis.
Less pronounced benefit was observed in focal segmental
glomerulosclerosis. Gradual response to treatment should
be expected with higher rates of remission after longer
follow-up.
References:
1.Evans R, Salama AD. Nephron Clin Pract 2014;126:97
2. Sinha A, Bagga A. A Nat Rev Nephrol 2013:9:154
3. Rood IM, Hofstra JM, et al. J. Adv Chron Kidney Dis 2014;21(2):166
53 ERA
CATEGORY H – Clinical nephrology, primary and secondary glomerulonephritis
173--MP
Poster printing financially
sponsored by:
Clinical Nephrology, primary and secondary glomerulonephritis.
Mario Laganovic
DOI: 10.3252/pso.eu.53era.2016