Introduction: The introduction of eculizumab has improved the outcome in patients with atypical hemolytic uremic syndrome (aHUS). The optimal treatment strategy is debated. Here, we report the results of the CUREiHUS study, a 4-year prospective, observational study monitoring unbiased eculizumab discontinuation in Dutch patients with aHUS after 3 months of therapy. Methods: All pediatric and adult patients with aHUS in native kidneys and a first-time eculizumab treatment were evaluated. In addition, an extensive cost-consequence analysis was conducted. Results: A total of 21 patients were included in the study from January 2016 to October 2020. In 17 patients (81%), a complement genetic variant or antibodies against factor H were identified. All patients showed full recovery of hematological thrombotic microangiopathy (TMA) parameters after the start of eculizumab. A renal response was noted in 18 patients. After a median treatment duration of 13.6 weeks (range 2.1–43.9), eculizumab was withdrawn in all patients. During follow-up (80.7 weeks [0.0–236.9]), relapses occurred in 4 patients. Median time to first relapse was 19.5 (14.3–53.6) weeks. Eculizumab was reinitiated within 24 hours in all relapsing patients. At last follow-up, there were no chronic sequelae, i.e., no clinically relevant increase in serum creatinine (sCr), proteinuria, and/or hypertension in relapsing patients. The low sample size and event rate did not allow to determine predictors of relapse. However, relapses only occurred in patients with a likely pathogenic variant. The cost-effectiveness analysis revealed that the total medical expenses of our population were only 30% of the fictive expenses that would have been made when patients received eculizumab every fortnight. Conclusion: It is safe and cost-effective to discontinue eculizumab after 3 months of therapy in patients with aHUS in native kidneys. Larger data registries are needed to determine factors associated with suboptimal kidney function recovery during eculizumab treatment, factors to predict relapses, and long-term outcomes of eculizumab discontinuation.
Bibliographical noteFunding Information:
This work was supported by grants from Zorgverzekeraars Nederland and ZonMw, “Goed Gebruik Geneesmiddelen” (project number 836031008). They did not have any role in data collection, analysis, or submission of this manuscript. The authors are very grateful to all patients for their willingness to participate in this study and to Laura Baas and Andrei Sarlea for performing all laboratory analysis. The authors also thank all research nurses and database managers for their important local management and data collection: Yvet Kroeze, Nienke Sonneveld, Dorien Standaar, Marja van Dijk, Judith Veen, Helma Dolmans, Katinka van Linschoten-Schinkel, Caro Fonkert, Maud van den Brocke, and Inger Kunnekes. Detailed participant data may be found in the supplemental data available with the online version of this article. For (any other) original data, please contact: Romy.Bouwmeester@radboudumc.nl. NCAJvdK, JFMW, and KLW designed the study, in close collaboration with WA, RdW, and EvK. All data were collected and monitored by RNB and CD. Laboratory and genetic results were evaluated by EBV and LPWJvdH. The cost-consequence analysis was designed and performed by KLW and EMA. All remaining data were analyzed and the manuscript was drafted by RNB, under critical supervision and review of NCAJvdK and JFMW. Recruitment and inclusion of patients and local study and clinical management were done by all members of the national aHUS working group (see author affiliations). NCAJvdk, JFMW, RNB, CD, MtA, RtH, LPWJvdH, EBV, and KLW attended and contributed to biweekly aHUS/CUREiHUS discussion meetings. All authors read, commented, and revised the manuscript before approval.
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