Changes in platelet counts within the first two weeks of treatment with Ultomiris (ravulizumab-cwvz) may predict long-term treatment response in patients with atypical hemolytic uremic syndrome (aHUS), according to a new study published in the Thrombosis Journal. The analysis of a Phase 3 clinical trial suggests that early platelet responses are linked to kidney improvements at the six-month mark.
Study Details and Findings
The study, titled "Correlation between a 2-week change in platelet count and clinical outcomes after the initiation of ravulizumab treatment in adult patients with atypical hemolytic uremic syndrome: post-hoc analysis of the phase III trial," was funded by Alexion AstraZeneca Rare Disease, the manufacturer of Ultomiris. Researchers analyzed data from 56 adult aHUS patients treated with Ultomiris. After six months, 30 patients achieved a complete thrombotic microangiopathy (TMA) response, indicated by reductions in kidney damage markers, decreased red blood cell destruction, and normalized platelet counts.
The results showed that 93.3% of patients with a complete TMA response experienced normalization of platelet counts within the first two weeks of Ultomiris treatment. In contrast, less than 27% of patients without a complete TMA response achieved platelet normalization in the same period. Similarly, 85.7% of patients achieving renal recovery (improvement in kidney function markers or discontinuation of dialysis) had normalized platelet counts within the first 15 days, compared to 23.8% of those who did not achieve renal recovery.
Clinical Implications
The researchers noted that while renal recovery in aHUS often takes longer than the 26-week study period, their findings suggest that early normalization of platelet count is associated with renal recovery within that initial treatment period. Statistical tests indicated that assessing platelet count normalization in the first two weeks could accurately predict renal recovery in over 80% of cases.
Background on aHUS and Ultomiris
aHUS is a rare disease caused by overactivity of the complement cascade, leading to blood clot formation in small vessels and damage to organs, particularly the kidneys. Ultomiris, a complement inhibitor, is an approved treatment for aHUS that resolves complement-mediated TMA and improves kidney function. However, not all patients respond to Ultomiris, and detecting its impact can take time.
Monitoring Platelet Counts
"This study demonstrated that the platelet response to [Ultomiris] in the early treatment period was associated with [the] achievement of renal [kidney] recovery within 26 weeks in patients with aHUS," the researchers wrote. Based on these findings, the team suggests that monitoring platelet counts early in treatment may help estimate long-term response in complement inhibitor-naïve adults with aHUS.
