Eculizumab Failure and the Off-Label Use of Ravulizumab

Introduction

Atypical Hemolytic Uremic Syndrome (aHUS) is a rare and severe disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. This case report highlights a catastrophic form of aHUS that was unresponsive to Eculizumab and required the off-label use of Ravulizumab, leading to successful hematologic recovery but progression to end-stage kidney disease.

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Case Summary

Patient Background:

• 40-year-old woman diagnosed with metastatic melanoma
• Underwent radical surgery and started Dabrafenib & Trametinib therapy
• Developed myopericarditis and was treated for heart failure
• Later experienced progressive renal failure, hemolytic anemia, and thrombocytopenia

Diagnosis & Initial Treatment:

• Peripheral smear showed schistocytes, suggesting aHUS
• C5B-9 assay confirmed aHUS with 331% deposition
• Started on Eculizumab (C5 inhibitor) but showed no improvement
• Condition worsened, leading to hemodialysis

Switch to Ravulizumab:

• Eculizumab-resistant case prompted an off-label switch to Ravulizumab
• 10 days post-administration: Increased haptoglobin, platelets, hemoglobin
• 20 days later: Complete hematologic recovery but irreversible kidney damage requiring dialysis

Medical Implications & Treatment Insights

Eculizumab Resistance in aHUS

• Majority respond well, but a few cases show poor efficacy.
• Possible reasons: Incomplete C5 blockade, genetic C5 variants, underlying drug-induced microangiopathy.

Why Ravulizumab?

• Long-acting C5 inhibitor with better blockade efficiency.
• Approved for aHUS treatment, though labeling restrictions in Italy limited access.

Chemotherapy as a Trigger for aHUS?

• Dabrafenib & Trametinib linked to vascular toxicity & cardiomyopathy.
• Possible drug-induced thrombotic microangiopathy as a triggering factor.

Key Takeaways

Early recognition of drug-induced TMA is crucial
Eculizumab may not be effective in all cases of aHUS
Ravulizumab could be a life-saving alternative in refractory cases Delayed treatment may lead to irreversible renal failure

Further Reading & References

Read the full study: DOI: 10.29328/journal.jcn.1001113
Explore more at Clinical Nephrology Journal

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