Eculizumab as a treatment for C3 glomerulopathy: a single-center retrospective study

Abstract

Background C3 Glomerulopathy (C3G) is a rare glomerular disease caused by dysregulation of the complement pathway. Based on its pathophysiology, treatment with the monoclonal antibody eculizumab targeting complement C5 may be a therapeutic option. Due to the rarity of the disease, observational data on the clinical response to eculizumab treatment is scarce. Methods Fourteen patients (8 female, 57%) treated for C3 glomerulopathy at the medical center of the University of Freiburg between 2013 and 2022 were included. Subjects underwent biopsy before enrollment. Histopathology, clinical data, and response to eculizumab treatment were analyzed. Key parameters to determine the primary outcome were changes of estimated glomerular filtration rate (eGFR) over time. Positive outcome was defined as > 30% increase, stable outcome as ±30%, negative outcome as decrease > 30% of eGFR. Results Eleven patients (78.8%) were treated with eculizumab, three received standard of care (SoC, 27.2%). Median follow-up time was 68 months (IQR: 45–98 months). Median eculizumab treatment duration was 10 months (IQR 5–46 months). After eculizumab treatment, five patients showed a stable outcome, six patients showed a negative outcome. Among patients receiving SoC, one patient showed a stable outcome, two patients showed a negative outcome. Conclusions The benefit of eculizumab in chronic progressive C3 glomerulopathy is limited.

C3G and Ig-MPGN—treatment standard

“…The anti-C5 monoclonal antibody eculizumab [ 28 ] (Figs 1 and 2 ) has been tested in single C3G or Ig-MPGN patients, small retrospective series [ 29 , 30 ] and in an off-on-off-on study, the EAGLE (Evaluating the Morphofunctional Effects of Eculizumab Therapy in Primary Membranoproliferative Glomerulonephritis) trial [ 31 ], with mixed results (Table 3 ). In some patients, proteinuria improved and renal function stabilized; however, the response to treatment was mostly partial in the long-term and about half patients did not benefit from the treatment.…”

Spatially resolved transcriptomic profiling for glomerular and tubulointerstitial gene expression in C3 glomerulopathy

“…4 While complement inhibitors have been proposed as potential diseasespecific therapies, recent studies of the C5 inhibitor eculizumab in C3G have not shown consistent efficacy. 5,6 The recent recognition of C3G as a distinct histopathological entity has allowed more precise characterizations of the underlying pathophysiology. Studies based on familial cases as well as animal models showed that constitutive activation of the alternative pathway is key to the development of the disease, mediated by factors including mutations in complement regulator genes and autoantibodies to enzymes in the complement cascade.…”