A Case of Complete Remission Rapidly Achieved with Pegcetacoplan in Mycophenolate-Prednisone-Resistant C3 Glomerulonephritis

Introduction: Complement C3 glomerulonephritis (C3GN) is a glomerular disease that can represent a treatment challenge. Emerging new therapies targeting the complement system show promise for improved renal outcome. We shared a case of a patient who achieved complete resolution of proteinuria and disease activity shortly after initiation of pegcetacoplan, a novel injectable targeted C3 inhibitor. Case Description: A 34-year-old man presented to the hospital with 1-week new-onset leg edema. Blood pressure was 186/99 mmHg. Examination revealed 2+ pitting edema in lower extremities. Laboratory testing revealed a serum creatinine (sCr) 1.3 mg/dL. Urine protein-to-creatinine ratio (UPCR) was 9.8 g/g. Urinalysis reported >100 RBCs/hpf, >100 WBCs/hpf. Urinary sediment microscopy (uSEDI) showed numerous white blood cell casts (WBCC) (up to 4/lpf), acanthocytes, RBC casts and lipid casts. Serum C3 <11 mg/dL, C4 39 mg/dL. A kidney biopsy was performed. Histopathology showed glomeruli with global endocapillary proliferation, 2 cellular crescents, and 10% IFTA by light microscopy; mesangial C3 (3+) and IgM (1+) by immunofluorescence, and subendothelial and subepithelial deposits by electron microscopy, consistent with C3GN. Treatment was started with mycophenolate 1 g bid and prednisone 20 mg qd, as well as lisinopril 40 mg qd. After 6 months of treatment, UPCR remained high at 5.2 g/g (range 1.8-6.3 g/g in the preceding 4 months) and the uSEDI remained consistently “active”. At this stage, stimulated by the announced positive results of the VALIANT trial, we opted to enroll the patient in an IRB-approved Early Access Program (EAP) to start treatment with pegcetacoplan. After 3 months of regulatory steps, the patient began treatment. Right before, UPCR was 2.2 g/g and uSEDI still “active” and unchanged. Six weeks into pegcetacoplan therapy, UPCR dropped to 0.3 g/g and the uSEDI showed marked reduction in activity with absence of WBCC, acanthocytes, RBC casts or lipid casts, and serum C3 normalized to 148 mg/dL. sCr remained fairly stable throughout the course of the treatment (1.1 – 1.5, latest 1.2 mg/dL). Patient tolerated pegcetacoplan without adverse effects. Discussion: This case highlights the role of potential role of pegcetacoplan for the treatment of C3GN refractory to other immunosuppressants.