Pegcetacoplan for the Treatment of Paediatric C3 Glomerulonephritis: A Case Report.

Complement 3 glomerulonephritis (C3GN) is a rare glomerular disease involving dysregulation of the complement system. We describe our experience using pegcetacoplan, an inhibitor of C3 and its activation fragment, C3b, for treatment-resistant C3GN in a 9-year-old boy referred for evaluation of refractory membranoproliferative glomerulonephritis. Despite treatment with intense immunosuppression (high-dose steroids, mycophenolate mofetil and calcineurin inhibitor), he continued to have high disease activity with low C3 levels (35 mg/dL), hypertension, symptomatic oedema, anaemia, and nephrotic-range proteinuria (e.g., urine protein-to-creatinine ratio [uPCR], 10 g/g; serum creatinine, 0.4 mg/dL). Given the concern for refractory C3GN following a steroid taper and tacrolimus trial with modest response (reduced proteinuria), we initiated pegcetacoplan 540 mg twice weekly for 1 week, followed by 648 mg twice weekly. Laboratory values before pegcetacoplan initiation included uPCR, 1.1 g/g, serum creatinine, 0.87 mg/dL, serum albumin, 4.7 g/dL, and serum C3, 30 mg/dL. Clinically significant improvements in serum C3 (142 mg/dL) and uPCR (422 mg/g) were observed within 1 week of pegcetacoplan initiation; within 3 months (uPCR, 322 mg/g; serum creatinine, 0.69 mg/dL; serum C3, 297 mg/dL), all immunosuppressive and antihypertensive medications were discontinued. No adverse effects of pegcetacoplan were reported. A kidney biopsy after 6 months of pegcetacoplan treatment showed mesangial and focal endocapillary proliferative glomerulonephritis with isolated C3c deposition by immunofluorescence, consistent with previous C3GN diagnosis. In this paediatric patient, compassionate use of pegcetacoplan was associated with rapid clinical improvement without adverse effects, and clinical effectiveness was confirmed by laboratory and histologic results within 6 months of treatment initiation.