Abstract: SA-PO261

Plasmapheresis, Rituximab, and Low-Dose Cyclophosphamide for Remission Induction Therapy in Severe ANCA-Associated Vasculitis

Session Information

Category: Glomerular

  • 1005 Clinical Glomerular Disorders

Authors

  • Gulati, Kavita, Imperial College London, London, United Kingdom
  • McAdoo, Stephen Paul, Imperial College London, London, United Kingdom
  • Galliford, Jack W., Imperial College London, London, United Kingdom
  • Griffith, Megan, Imperial College London, London, United Kingdom
  • Cairns, Tom, Imperial College London, London, United Kingdom
  • Pusey, Charles D., Imperial College London, London, United Kingdom
Background

Rituximab (RTX) is an established treatment for remission-induction in ANCA-associated vasculitis (AAV), though data regarding its use in immediately organ- or life-threatening disease are limited. We have studied the use of RTX as adjuctive therapy to plasmapheresis (PEX), cyclophosphamide (CYC) and oral steroids in patients presenting with diffuse alveolar haemorrhage (DAH) or severe renal failure (presenting requirement for dialysis or serum creatinine >500μ/L).

Methods

This is a cohort study of patients treated for severe AAV between 2011-15 with a combination of PEX, low dose pulsed i.v. CYC (6x500-750mg) and RTX (2x1g after completion of PEX) and tapered oral corticosteroids (initial dose 1mg/kg, maximum 60mg od) without intravenous steroids. Maintenance therapy was commenced at 3 months with azathioprine (MMF if intolerant) and patients received prophylactic treatment for PCP, peptic ulcer disease and osteoporosis. Data are reported as median & IQR.

Results

Thirty patients have been treated with this regimen, with median follow-up 2.1 yrs. Median age was 62 yrs (IQR 55-75); 50% were PR3-ANCA+ve, 50% MPO-ANCA+ve. Presenting BVAS was 21 (16-25), creatinine 452 μmol/L (338-590), and 43% required dialysis. DAH was present in 43%. Patients received 7 (7-10) plasma exchanges, and cumulative RTX and CYC doses were 2g (all patients) and 3g (2.5-3.5), respectively. At 6 months, 90% of patients were in remission (BVAS=0). All patients achieved B cell depletion (<1 cell/μL) and 83% became ANCA negative at median 5.1 months. The median time to B cell repopulation (>10 cell/μL) was 35 months. Sustained B cell depletion was associated with low rates of relapse during long-term follow up: at 1, 3 and 5 years, 96%, 84% and 75%, of patients, respectively, were in sustained remission. The serious infection rate was 0.4/yr and 6 patients developed hypoIgG. Renal survival was 72%, 64%, 64% at 1, 3 and 5 years. Overall patient surival was 93%, 79% 79% at the same respective time points.

Conclusion

This combination regimen was an effective remission-induction strategy in severe AAV. Long-term relapse rates and renal and patient survival were favourable in a cohort of patients presenting with life-threatening disease manifestations. Combination regimens warrant further investigation in severe AAV.