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Kant S, Habbach A, Gapud EJ, Manno RL, Gattu R, Seo P, Geetha D: Sequential Therapy for Remission Induction in Severe Antineutrophil Cytoplasmic Autoantibody-Associated Glomerulonephritis. Am J Nephrol 2019 DOI 10.1159/000503318
The optimal treatment strategy for induction of a remission in antineutrophil cytoplasmic antibody-associated (ANCA) vasculitis with severe renal involvement is in a state of flux as new data emerges from clinical trials and observational studies.
Kant and associates examined a novel regimen in a retrospective analysis of 9 patients with new or relapsing ANCA associate vasculitis (AAV) who presented with severe renal disease (dialysis dependency or an estimated glomerular filtration rate (eGFR) of 11‑22ml/min/1.73m2). Six were anti-MPO and 3 were anti-PR3 subtypes. All patients were treated with 3 daily IV methylprednisolone pulses, 1000mg each, and then 60mg of oral prednisone tapered rapidly to 5mg by month 3. The patients were initially given oral cyclophosphamide which was stopped when the vasculitic activity improved and the serum creatinine began to decline (at between 28 and 53 days after starting therapy) and rituximab, 375mg/m2 was given 4 times a week. Plasmapheresis was given to 3 patients for pulmonary involvement.
All patients went into clinical remission and all but one patient recovered sufficient renal function to avoid dialysis. The eGFR at 12 months was 16‑94ml/min/1.73m2.
While retrospective and uncontrolled, these results suggest that when severe renal disease is present (chronic kidney disease (CKD) stages 4–5). Clinical remission and avoidance of permanent end stage kidney disease (ESKD) is possible. Whether the sequential protocol with rituximab following short term oral cyclophosphamide use (median 35 days) and rapid steroid tapering is an “optimal” strategy cannot be defined by such a small study (n=9) with short term follow up. A properly designed randomized trial is needed to confirm these results. Initial therapy with rituximab and steroids alone might give equivalent results. It is doubtful that plasmapheresis had much to do with the good results observed in this small cohort.
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