(361) Real-world demographics, clinical characteristics, and medication utilization in biopsy-confirmed primary C3 glomerulopathy: A 20-year single-center EHR cohort study

Background: : C3 glomerulopathy (C3G) is a rare progressive nephropathy with limited real-world characterization.

Objective: : We describe baseline demographics, clinical features, and medication utilization in primary C3G using EHR data.

Methods: : In this retrospective cohort study (2002–2022), we identified 56 biopsy-confirmed primary C3G cases from nference nSights de-identified EHR database, representing 7.3 million patients primarily across five U.S. states (MN, WI, IA, FL, and AZ). C3G was defined by ≥2 structured ICD codes ≥15 days apart and/or ≥2 positive NLP mentions (or one of each) ≥15 days apart, plus biopsy confirmation within ± 60 days of the earliest qualifying ICD code or positive NLP mention. Patients with secondary etiologies (e.g., infections, monoclonal gammopathies, systemic diseases, neoplasms) were excluded. Baseline demographics, comorbidities, clinical manifestations, and lab measurements were captured in the 12 months before diagnosis. Medication orders for disease-related classes (immunosuppressants and renin-angiotensin system blockers) and select individual agents were captured during baseline and the first 12 months follow up.

Results: : The cohort (N=56) was young (median age 22 years, IQR 13.5) with 27% in the pediatric age group ( < 18 years); half were female, and the majority were White (86%). Comorbidity burden was low (Elixhauser score 0 in 59%, 5–10 in 32%). In the baseline period, mean eGFR was 69.9 ± 45.8 mL/min/1.73 m², 43% exhibited proteinuria ≥1 g/24 h (25% nephrotic-range ≥3 g/24 h), and 23% had hematuria. 73% of patients underwent 24-hour protein collection at baseline, whereas spot ACR/PCR testing was less common (21%).

At baseline, only 21.4% of patients had at least one medication order (mean 1.75 ± 0.87 orders/patient). After diagnosis, 75% of patients were started on therapy, with mean orders rising to 2.19 ± 1.38 by 12 months. Monotherapy accounted for 35.7% of regimens; 2/3-agent therapy comprised 23.2%; and intensive combinations (4–5 agents) were used in 14.3% (1.8% received ≥6 agents). Class-specific use increased substantially: RAS blockade (ACE-I/ARB) rose from 12% at baseline to 51%, corticosteroids from 11% to 41%, and mycophenolate mofetil from 2% to 21% at 12 months.

Conclusions: : Primary C3G presents with heterogeneous renal impairment, and is often managed with multi-agent therapy, imposing substantial patient burden (high pill counts, frequent monitoring, drug-drug interactions) and adherence challenges, underscoring the need for more effective therapies.

Sponsorship:: Apellis Pharmaceuticals USA, Inc.