Abstract: FR-PO904
Outcome of First Relapse After Eculizumab Withdrawal in Atypical Hemolytic Uremic Syndrome: The CUREiHUS Study
Session Information
- Glomerular Diseases: Membranous Nephropathy, SLE, Complement
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1203 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Duineveld, Caroline, Radboudumc, Nijmegen, Netherlands
- Bouwmeester, Romy N., Radboudumc, Nijmegen, Netherlands
- Wijnsma, Kioa L., Radboudumc, Nijmegen, Netherlands
- Van De Kar, Nicole, Radboudumc, Nijmegen, Netherlands
- Wetzels, Jack F., Radboudumc, Nijmegen, Netherlands
Group or Team Name
- CUREiHUS study group
Background
Eculizumab was introduced as lifelong therapy for patients with aHUS. However, the costs of therapy and potential side effects have stimulated early drug withdrawal. The safety of an early withdrawal strategy is debated, since relapses may cause chronic kidney injury. In the Netherlands eculizumab is used according a restrictive treatment regime, with a preference to withdraw or taper the drug three months after start of therapy. Here, we present an interim analysis of the outcome of patients with a first relapse.
Methods
We evaluated outcome in all aHUS patients in whom eculizumab was tapered or withdrawn, and developed a (suspected) relapse necessitating renewed eculizumab therapy. Serum creatinine, eGFR (CKD-epi) and protein-creatinine ratio’s at 6 and 9 months after relapse and last follow-up were compared with baseline.
Results
We evaluated 34 patients (20 F, 14 M; median age 35 years, IQR 34) with aHUS, in whom eculizumab was tapered or withdrawn. Fourteen patients (41%), including 3 children, had a relapse. Of these, 93% were known with a genetic variant in complement genes. Eight patients had a kidney transplant. Restart of eculizumab was effective in most patients, with no significant difference between eGFR at baseline (median 42.6 ml/min/1.73m2, IQR 40) at 6 months (40.5 ml/min/1.73m2, IQR 48), 9 months (36.6 ml/min/1.73m2, IQR 42) after relapse, and at the end of follow-up (35.6 ml/min/1.73m2, IQR 53). At the end of follow-up (18 months, range 2-31), one patient with multiple relapses had developed ESRD, with notable and unexplained cystic malformation in both kidneys. In four other patients eGFR had decreased ≥20% compared to baseline. All four had received a kidney transplant, had moderate-severe CKD at baseline, with eGFR affected by viral infections and rejection episodes.
Conclusion
Eculizumab withdrawal was successful in 53% (18/34) of the patients. In 41% of the patients a relapse occurred. Overall, there was no safety signal. Still, the number of patients is limited. Patients with a kidney transplant, and/or moderate-severe CKD may be at risk for sustained kidney injury.
Funding
- Government Support - Non-U.S.