Abstract: PO0239
Exploratory Diagnostic and Prognostic Biomarkers in Adults with Atypical Hemolytic Uremic Syndrome (aHUS): Analysis of the Phase 3 Study of Ravulizumab (NCT02949128)
Session Information
- AKI: Clinical, Outcomes, and Trials
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 102 AKI: Clinical, Outcomes, and Trials
Authors
- Cammett, Tobin J., Alexion Pharmaceuticals Inc, Boston, Massachusetts, United States
- Garlo, Katherine, Alexion Pharmaceuticals Inc, Boston, Massachusetts, United States
- Millman, Ellen E., Alexion Pharmaceuticals Inc, Boston, Massachusetts, United States
- Rice, Kara, Alexion Pharmaceuticals Inc, Boston, Massachusetts, United States
- Faas, Susan, Alexion Pharmaceuticals Inc, Boston, Massachusetts, United States
Background
Validated biomarkers for diagnosis and monitoring of patients with complement-mediated thrombotic microangiopathy (CM-TMA) are not clinically available. Characterization of biomarkers in patients with aHUS, a form of CM-TMA, may inform diagnosis, treatment decisions and monitoring for patients with other types of CM-TMA.
Methods
Using data from the phase III study of ravulizumab (terminal C5 complement inhibitor) in adults with aHUS (NCT02949128), baseline (BL; prior to treatment) serum, plasma and urine biomarker levels in patients were compared with levels in healthy volunteers (HV), and evaluated for associations with kidney function (e.g. estimated glomerular filtration rate [eGFR] and urine protein/creatinine [Cr] ratio [UPCR]) at BL and 26 weeks post-treatment initiation. Regression coefficients and p-values (two-sided t-test) are reported.
Results
This analysis included 55 patients: median age 39 (range 19–76) years; 67% female; 53% White, 27% Asian. Specific BL biomarkers were elevated compared with HV, and associations between BL biomarker levels and both BL eGFR and BL UPCR were identified (Table 1). BL plasma complement factor Ba was associated with eGFR changes after 26 weeks of ravulizumab treatment, while urine sC5b-9, sC5b-9/Cr, Ba and Ba/Cr were associated with UPCR changes after 26 weeks of treatment.
Conclusion
The complement biomarkers Ba (plasma and urine) and sC5b-9 (urine) were associated with kidney function in patients with aHUS at baseline and over 26 weeks of treatment with anti-C5 therapy. Such biomarkers demonstrate diagnostic potential in CM-TMA and may predict renal response to terminal complement inhibition.
Table 1: Baseline biomarkers
| Biomarker | Patients with elevated BL biomarkers* % (n/N) | BL biomarker associations with kidney function measures (BL) Regression coefficient (p-value) | BL biomarker associations with kidney function measures (26-week change from BL) Regression coefficient (p-value) | ||
| eGFR | UPCR | eGFR | UPCR | ||
| Urine cystatin C/Cr (ng/mg Cr) | 100.0 (36/36) | -0.25 (0.0002) | 0.42 (0.0048) | -2.28 (0.4290) | -9.72 (0.2385) |
| Plasma Ba (ng/ml) | 97.7 (42/43) | -0.55 (<0.0001) | 1.25 (0.0001) | -13.98 (0.0085) | -27.42 (0.1021) |
| Urine cystatin C (ng/ml) | 97.6 (41/42) | -0.25 (<0.0001) | 0.51 (<0.0001) | -0.62 (0.7788) | -7.38 (0.2103) |
| Urine Ba (ng/ml) | 97.5 (39/40) | -0.28 (<0.0001) | 0.73 (<0.0001) | 1.41 (0.5825) | -16.07 (0.0090) |
| Urine Ba/Cr (ng/mg Cr) | 97.1 (34/35) | -0.31 (<0.0001) | 0.77 (<0.0001) | 2.40 (0.3957) | -17.28 (0.0110) |
| Urine sC5b-9**/Cr (ng/mg Cr) | 96.9 (31/32) | -0.10 (0.0391) | 0.45 (<0.0001) | 1.91 (0.3650) | -21.46 (<0.0001) |
| Urine sC5b-9** (ng/ml) | 88.1 (37/42) | -0.12 (0.0021) | 0.44 (<0.0001) | -0.79 (0.5862) | -16.03 (<0.0001) |
| Plasma sC5b-9 (ng/ml) | 79.1 (34/43) | 0.19 (0.1430) | -0.25 (0.3712) | -3.17 (0.5269) | 15.91 (0.1830) |
*compared with observed maximum for HV; **urine sC5b-9 is undetectable in HV, therefore HV values were set at ½LLOQ
Funding
- Commercial Support –