email: emilio.besada@uit.no
Rituximab (RTX) is an anti-CD20 antibody used in ANCA-associated vasculitis (AAV) for induction and maintenance of remission.
The objective of this study is to determine the effects of CYC on Ig levels in patients treated with long- term pre-emptive RTX maintenance.
Objective:
Results:
During RTX maintenance therapy in AAV, the largest Ig decrease occurs after the first infusion round, but Ig levels continue to decrease thereafter albeit at a lower speed.
A high cumulative CYC dose (>50g) as well as combining RTX with CYC at initiation leads to larger decline of Ig during RTX maintenance therapy
Conclusion:
Cyclophosphamide effect on immunoglobulins levels in AAV patients treated with long-term pre-emptive rituximab
maintenance.
Besada E ¹, Koldingsnes W ², Nossent JC ¹ ³
1 Bone and joint research group, Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway 2 Department of Rheumatology, University Hospital North Norway, Tromsø, Norway
3 Division of Medicine, Royal Darwin Hospital, Department of Health, NT, Australia
Methods:
Retrospective study of 38 patients (35 with GPA and with 3 with CSS) treated with RTX between April 2004 and September 2011 for active disease. 58% of the patients had renal involvement. The cumulative cyclophosphamide (CYC) dose was 14g (0-250). Twelve patients (32%) were treated with combination CYC-RTX at initiation.
RTX was initiated as two 1g infusion 2 weeks apart (RA protocol) and thereafter 2g RTX was administered annually to achieve long-term B cell depletion. Patients were closely monitored during 46.5 (2-88) months follow-up with clinical and serological surveillance. They received a median of 5 (1-10) rounds of RTX for a cumulative dose of 8g (2-13)
0 2 4 6 8 10 12
1(38) 2(34) 3(30) 4(29) 5(26) 6(18) 7(11) 8(7) 9(3) Number of rounds (number of patients)
Total Ig g/L
All patients
Patients still treated with RTX at last visit
Patients that discontinued RTX due to hypogammaglobulinemia Median serum Ig levels declined continuously but not in a linear
fashion after each RTX re-treatment
Median decrease in immunoglobulins classes and total immunoglobulins after the first (33 patients included), the second (30 patients) and the third round (28 patients) as well at last visit (38 patients).
Ig decline after first round
Ig decline after second
round
Ig decline after third round
Overall decline from baseline to
last visit
IgG g/L 1.70 0.20 0.05 2.80
IgA g/L 0.32 0.06 0.03 0.40
IgM g/L 0.25 0.03 0.03 0.39
Total Ig g/L
2.35 0.27 0.39 3.46
The largest decline in Ig level occurred after the first RTX round.
Patients with a cumulative CYC dose > 50g (29%): Patients receiving initial RTX in combination with CYC (32%):
0 2 4 6 8 10 12
Prior RTX After 1.
round
After 2.
round
After 3.
round
Nadir level under maintenance Patients with cumulative CYC > 50g Patients with cumulative CYC <50g
Had lower levels of total Ig after the first 3 RTX rounds and had also lower levels during RTX maintenance.
P=0.038 P=0.158
P=0.019 P=0.016 P=0.002
0 0,5 1 1,5 2 2,5 3 3,5 4 4,5 5
IgG IgA IgM Total Ig
RTX combined with CYC at initiation RTX without CYC at initiation
Had bigger overall decline from baseline in all Ig classes.
P=0.028
P=0.028 P=0.011
P=0.030
