Session Information
Date: Sunday, November 8, 2015
Title: Vasculitis Poster I
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose:
The ‘Euro-Lupus’ low dose cyclophosphamide (CPM) protocol has been validated for use in lupus nephritis patients in randomised controlled trials. A recent controlled study of this protocol by the French vasculitis group has shown favourable results in ANCA positive vasculitis. Our aim is to assess the efficacy and safety of low dose CPM in systemic vasculitides patients.
Methods:
We retrospectively assessed 26 patients with systemic vasculitis at the Louise Coote lupus Unit at Guy’s and St Thomas’ Hospital who received low dose CPM induction therapy along with corticosteroids during the last 15 years. All patients fulfilled the ACR/Chapel Hill classification criteria for Granulomatosis with Polyangiitis, eosinophilic Granulomatosis with Polyangitis and Microscopic Polyangitis. All patients received 3 pulses of methylprednisolone 500mg and 6 pulses of CPM infusion 500 mg with mesna fortnightly as induction therapy. Subsequently Azathioprine, Methotrexate or Mycofenolate Mofetil were used as remission maintaining agents. Data regarding inflammatory markers Erythrocyte Sedimentation Rate (ESR) and C-reactive protein (CRP), Birmingham Vasculitis Activity Score (BVAS) and Vasculitis Damage Index (VDI) scores were assessed at baseline and after 6, 12, 24, 60, 120 and 180 months. Data on all relapses, organ involvement, duration of remission, corticosteroid requirement, repeat CPM infusions, Rituximab and adverse events were recorded.
Results:
26 patients (13 males, 13 females) were assessed. 22 were Caucasians, 2 mixed ethnicity and 2 Asians. Median age was 54 years. 20 patients had positive ANCA antibodies (15 anti-PR3, 5 anti-MPO). 6 were ANCA negative. The median disease duration prior to induction therapy was 3.12 years. 10 patients had pulmonary involvement (pulmonary hemorrhages, haemoptysis, cavitating lung lesions, nodules), 9 necrotizing crescentic glomerulonephritis, 1 myocarditis, 7 neurological manifestations (raised ICP, occipital masses, mononeuritis multiplex), 3 orbital granulomas, 1 necrotizing scleritis, 2 otitis media with hearing loss and 1 bowel ischaemia. Co-morbidities were antiphospholipid syndrome (2 patients), positive lupus anticoagulant (2), type 2 diabetes mellitus (1), past Tuberculosis (1) and sleep apnoea (1). All patients received tapered doses of oral prednisolone (median dose 30 mg) following the induction regimen.
Median duration of remission was 2.40 years. There was improvement in BVAS, CRP and ESR. 10 patients had relapses over 5 years. 5 patients required repeat CPM pulses for flares and 7 received Rituximab. 12 adverse events were recorded. Renal function remained stable over the years. 1 death has been recorded (See Table)
Conclusion:
Low dose intravenous infusion of CPM in combination with steroids may be effective in achieving remission in systemic vasculitides. This regimen may have fewer adverse events than conventional therapy with high dose CPM.
Table:
|
Time (1/12=1month) |
Pre therapy |
6/12 |
12/12 |
24/12 |
60/12 |
120/12 |
180/12 |
|
BVAS |
15.52 (n=23) |
4.54 (n=22) |
5.42 (n=19) |
9.00 (n=9) |
4.40 (n=5) |
2.00 (n=3) |
2.00 (n=2) |
|
ESR (mm/hr) |
28.77 (n=22) |
18.26 (n=19) |
24.52 (n=17) |
31.00 (n=6) |
9.60 (n=5) |
8.50 (n=2) |
8.50 (n=2) |
|
CRP (mg/L) |
45.54 (n=22) |
15.21 (n=19) |
12.84 (n=19) |
16.50 (n=6) |
7.60 (n=5) |
1.00 (n=2) |
1.00 (n=2) |
|
Creatinine (umol/L) |
84.52 (n=21) |
91.50 (n=20) |
94.20 (n=20) |
107.28 (n=7) |
105.83 (n=6) |
129.50 (n=2) |
139.00 (n=2) |
|
e GFR (ml/min) |
79.15 (n=20) |
76.56 (n=16) |
74.78 (n=18) |
67.50 (n=8) |
70.75 (n=4) |
46.00 (n=2) |
44.00 (n=2) |
|
PCR |
72.44 (n=16) |
20.75 (n=12) |
17.62 (n=8) |
31.00 (n=4) |
0 (n=1) |
342.00 (n=1) |
181.00 (n=1) |
|
Remission (BVAS =0) |
|
N=4 |
N=3 |
N=1 |
N=1 |
N=1 |
N=1 |
|
Prednisolone dose (mg) |
30 (n=21) |
14 (n=20) |
13 (n=21) |
14 (n=8) |
9 ( n=5) |
6 (n=2) |
7.5 (n=2) |
|
Relapses |
|
N=2 |
N=5 |
N=1 |
N=2 |
|
N=1 |
|
Rituximab therapy |
|
N=2 |
N=3 |
N=2 |
|
N=1 |
|
|
Repeat CYP therapy |
|
N=3 |
N=2 |
N=1 |
|
|
|
|
VDI (median) |
1.76 (n=21) |
2.60 (n=20) |
2.67 (n=18) |
3.62 (n=8) |
2.4 (n=5) |
1.33 (n=3) |
1.00 (n=2) |
|
Adverse events |
|
UTIs (recurrent) (n=1), SCC (n=1), cataract (n=1) |
Reactivation of variccella zoster/ Shingles (n=1) |
Death (n=1), steroid induced diabetes/ pancreatitis (n=1) |
Squamous cell carcinoma (n=1) |
MI (n=1) |
Hurtle cell tumour (n=1 |
To cite this abstract in AMA style:
Grigoriou A, Sangle S, Ling C, D'Cruz DP. a Retrospective Analysis of Low Dose Cyclophosphamide Therapy in Systemic Vasculitides [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/a-retrospective-analysis-of-low-dose-cyclophosphamide-therapy-in-systemic-vasculitides/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-retrospective-analysis-of-low-dose-cyclophosphamide-therapy-in-systemic-vasculitides/