Work

Real-World Effectiveness of Ravulizumab Among C5 Inhibitor-Naive Patients With Atypical Hemolytic Uremic Syndrome: A Physician Panel-Based Chart Review (aHUS IMPACT Study)

Year: 2025

Type: article

Abstract: Rationale & Objective Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) caused by complement dysregulation. Ravulizumab, a complement C5 inhibitor (C5i), is approved for aHUS; however, published evidence in a real-world setting is limited. Study Design Retrospective, longitudinal, physician panel-based chart review. Setting & Population C5i-naive adults with aHUS in the United States treated with ravulizumab. Physicians randomly selected 1-5 patients who had ≥6 months of follow-up after ravulizumab initiation; patients who died within 6 months of initiation were eligible. Exposure(s) or Predictor(s) Ravulizumab. Outcomes The clinical outcomes evaluated included hematologic and renal outcomes, complete TMA response (a composite hematolgic/renal endpoint), and dialysis use. Analytical Approach Descriptive statistics, Kaplan-Meier estimators, and generalized linear models. Results Overall, 79 C5i-naive adults with aHUS (enrolled by 31 physicians) initiated ravulizumab and were included in the study. Statistically significant improvements from baseline occurred as early as day 4 (lactate dehydrogenase and percent change in serum creatinine; both P < 0.001) and day 8 (platelet count; P < 0.001). The proportions of patients with normalization of platelet counts and lactate dehydrogenase levels, and ≥25% improvement in serum creatinine levels, were 14 out of 67 (21%), 12 out of 58 (21%), and 10 out of 65 (15%) at day 4, and 40 out of 48 (83%), 35 out of 38 (92%), and 42 out of 48 (88%) at 12 months after ravulizumab initiation, respectively. Complete TMA response rates were 60% and 68% within 6 and 12 months after ravulizumab initiation, respectively, and the median (interquartile range) time to complete TMA response was 3.1 (1.0-14.0) months. Of the 20 patients who received any dialysis at baseline, 14 (70.0%) did not have dialysis during follow-up. Limitations The study design relies on available medical record data and has potential responder bias. Conclusions This study supports the immediate and sustained benefits of initiating ravulizumab in patients with aHUS as seen by the early response and continued improvement in clinical outcomes. Plain-Language Summary This study evaluates the use of a treatment called ravulizumab for atypical hemolytic uremic syndrome (aHUS), a rare disease that causes clots in small blood vessels and can lead to kidney failure. Researchers reviewed the medical records of 79 adults with aHUS in the United States who were treated with ravulizumab and had never used similar treatments before. Significant improvements in laboratory measures including lactate dehydrogenase and serum creatinine levels occurred by day 4, and in platelet count by day 8. At month 12, most patients had normalized platelet counts and lactate dehydrogenase levels, and improved serum creatinine levels. Many patients were able to stop receiving dialysis during the follow-up period. The results suggest that ravulizumab provides immediate and lasting benefits for patients with aHUS.

Source: Kidney Medicine

DOI: 10.1016/j.xkme.2025.101198