#2066 Treatment patterns of patients with complement 3 glomerulopathy (C3G): a retrospective linked electronic medical record (EMR) and claims analysis
Authors: Ndife Briana , Aldworth Carolina , Murphy Kathleen , Thakkar Karishma , Olson Stephen , Nagelhout Elizabeth , Boyd Marley , Leiras Claudia , Gor Deval 
Published: May 2024

Abstract

Background and Aims
C3G is characterised by C3 deposition in the glomeruli, caused by dysregulation of the alternative complement pathway. Currently, there are no approved therapies for C3G. The aim of this analysis was to evaluate treatment patterns in patients with C3G in the United States (US).

Methods
This was a retrospective cohort study of patients with C3G, with an EMR and linked pharmacy and medical claims data in the US HealthVerity database, who were diagnosed between Jan 1, 2017 and Sep 30, 2021 and aged ≥12 years at diagnosis. Included patients had database records for ≥12 months before (baseline period) and after (follow-up period) the index date (date of first C3G diagnosis, identified by International Classification of Diseases 10th Revision Clinical Modification [ICD-10-CM] and Systematized Nomenclature of Medicine [SNOMED] diagnosis codes). Endpoints included: proportion of patients receiving a treatment, including supportive care (angiotensin-converting enzyme inhibitors [ACEi]/angiotensin II receptor blockers [ARB]), immunosuppressants (IM; including corticosteroids [CS]/glucocorticoids [GC] and mycophenolate mofetil [MMF]), and eculizumab; proportion of patients discontinuing treatment; and duration of treatment. Discontinuing treatment was defined as the absence of a subsequent claim for medication for ≥60 days. Results were assessed using descriptive statistics and analysed by Fisher's exact test, Mann–Whitney U test, or Student's t-test, as appropriate.

Results
The final cohort included 683 patients. Overall, 346 (50.7%) patients had ≥1 treatment record for C3G during follow-up (median follow-up 24.0 months; median time from index to first treatment 1.1 months). Mean age (standard deviation) of treated and untreated patients was 47.7 (19.4) and 39.6 (18.0) years (P &lt; 0.0001), respectively; 54.3% of treated patients and 72.7% of untreated patients were female (P &lt; 0.0001). Comorbidities reported in treated and untreated patients, respectively, included: hypertension (75.1% and 33.5%; P &lt; 0.0001) and type II diabetes (34.7% and 12.8%; P &lt; 0.0001). Baseline proteinuria data were available for 39 (11.3%) treated patients and 11 (3.3%) untreated patients (P &lt; 0.0001). Median (lower quartile, upper quartile) proteinuria levels were 1.9 (0.7, 3.3) g/g and 0.2 (0.1, 2.3) g/g for the treated and untreated populations, respectively (P = 0.05).
Among treated patients (n = 346), most (76.0%) received an ACEi/ARB alone in the first line, 14.2% received IM alone, and 5.8% received concomitant ACEi/ARB and IM (Table 1). A small number of remaining patients received a sodium-glucose cotransporter-2 inhibitor (SGLT2i) ± ACEi/ARB (2.9%), or eculizumab ± IM (1.2%). Less than half of treated patients (43.9%) received second-line therapy, and 17.6%, 6.6%, and 2.0%, respectively, received subsequent lines of treatment. Among treated patients, the most common treatment sequence was ACEi/ARB alone in the first line, without subsequent lines of therapy (42.2%); 30.9% of treated patients received IM (alone or in combination with other treatments) at any time during follow-up. Median duration of treatment in months (95% confidence interval) in any line was 14.9 (9.9, 18.4) for ARB, 8.6 (7.5, 11.1) for ACEi, 7.4 (3.3, 22.6) for SGLT2i, 4.7 (3.0, 6.6) for MMF, and 1.0 (0.9, 3.0) for CS/GC. During follow-up, 225 (65.0%) patients discontinued treatment: 22 (9.8%) and 203 (90.2%) patients restarted and did not restart therapy, respectively.

Conclusions
These real-world data show that only half of patients with C3G had a record of treatment during follow-up. Compared with the untreated population, patients who received treatment were older, more likely to be male, and more likely to have hypertension or type II diabetes. Among treated patients, the most common treatment sequence was supportive care with an ACEi/ARB alone, and less than one-third received IM at any time during follow-up. Use of the complement inhibitor, eculizumab, was low in this population. A large proportion of patients discontinued treatment during follow-up; given the progressive nature of C3G, these data may highlight the need for novel therapies in the treatment of C3G.