Abstract: PUB211
Complement Inhibition with a Short Course of Eculizumab for Refractory Vasculitis
Session Information
Category: Glomerular Diseases
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Uriol Rivera, Miguel, Hospital Universitari Son Espases, Palma de Mallorca, Illes Balears, Spain
- Obrador, Aina, Hospital Universitari Son Espases, Palma de Mallorca, Illes Balears, Spain
- Jimenez, Sonia, Hospital Universitari Son Espases, Palma de Mallorca, Illes Balears, Spain
Background
Systemic vasculitis (SV) is a life-threatening disease and, in some cases, refractory to intensive multi-immunosuppressant drugs.
Complement hyperactivation has gained interest in the pathogenesis of the SV.
We report the efficacy of the short course of C5-inhibitor (eculizumab) in refractory cases of lupus nephritis (r-LN) and refractory ANCA-associated glomerulonephritis (r-AGN).
Methods
In this retrospective study, nine consecutive patients were included (r-LN:n=3 and r-AGN:n=6). All patients were previously treated with three or more drugs: corticosteroids(n=9), mycophenolate(n=9), rituximab(n=8), immunoglobulins(n=5), therapeutic plasma exchange (n=4), cyclophosphamide(n=1), and belimumab(n=1). Eculizumab was considered for use in off-label indication in patients with progressive renal deterioration (worsening creatinine, protein-to-creatinine ratio) or developing a high-risk lethal complication after the induction immunosuppressive therapy. The histologic lesson observed were: a) r-LN: Type VI (n=1), Type V (n=1), and type IV (n=1), and b) r-AGN: sclerotic (n=3), and malignant hypertension+/-thrombotic microangiopathy (n=1), in two patients who developed pulmonary haemorrhage, no renal biopsy was performed.
Results
Mean age (SD): 54(17) years. Median (min-max) of follow-up: 23(2-48) months. Overall, 2(22%) patients are in chronic renal replacement program (one r-AGN patient who was dialysis dependent at presentation, and presented a complement H mutation, and one r-LN within 12 months after the onset eculizumab). 8 patients showed hypocomplementemia. As a whole the mean (95%CI) eGFR (EPI-CKD), increased: 8.0 (-3.0 to 19.1) ml/min/1.73m2 (P = 0.13). In r-AGN, the mean (95%CI) eGFR increased :13(-1.8 to 28,25), P= 0.07; while in r-LN, a slight change was observed: -2.1(-24.8 to 20.59), P = 0.72. The median(p25-p75) protein-to-creatinine ratio decreased from 2.6 (1.6-5.5) to 0.6(0.4-1.2) mg/mg (P= 0.01). The eculizumab doses [median(p25-p75)] required in r-LN and rAGN patients were: 8400 (7800-10200) mg and 3150 (2475-5700) mg, respectively. No major side effects were recorded.
Conclusion
The coadjuvant complement inhibition with eculizumab stabilized or increased renal function and decreased proteinuria significantly in refractory vasculitis. The short course of eculizumab seems to be highly effective in r-AGN, and also was associated with lower doses needed.