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

## TL;DR

This study shows that ravulizumab, a treatment for a rare blood disorder called aHUS, leads to quick and lasting improvements in patients' health.

## Contribution

The study provides real-world evidence of ravulizumab's effectiveness in C5 inhibitor-naive aHUS patients.

## Key findings

- Significant improvements in lactate dehydrogenase and serum creatinine levels occurred by day 4 of treatment.
- Platelet counts improved by day 8, with most patients normalizing within 12 months.
- 70% of patients who needed dialysis at baseline no longer required it during follow-up.

## Abstract

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.

Retrospective, longitudinal, physician panel-based chart review.

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.

Ravulizumab.

The clinical outcomes evaluated included hematologic and renal outcomes, complete TMA response (a composite hematolgic/renal endpoint), and dialysis use.

Descriptive statistics, Kaplan-Meier estimators, and generalized linear models.

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.

The study design relies on available medical record data and has potential responder bias.

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.

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.