Real-World Effectiveness of Ravulizumab Among C5 Inhibitor-Naive Patients With Atypical Hemolytic Uremic Syndrome: A...

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.