Melissa Muff-Luett1, Keia R Sanderson2, Rachel M Engen3, Rima S Zahr4, Scott E Wenderfer5, Cheryl L Tran6, Sheena Sharma7, Yi Cai8, Susan Ingraham9, Erica Winnicki10, Donald J Weaver11, Tracy E Hunley12, Stefan G Kiessling13, Meredith Seamon14, Robert Woroniecki15, Yosuke Miyashita16, Nianzhou Xiao17, Abiodun A Omoloja18, Sarah J Kizilbash19, Asif Mansuri20, Mahmoud Kallash21, Yichun Yu2, Ashley K Sherman22, Tarak Srivastava23, Carla M Nester24. 1. Department of Pediatrics, Pediatric Nephrology, University of Nebraska Medical School, Children's Hospital and Medical Center, 8200 Dodge St., Omaha, NE, 68114-4113, USA. mluett@childrensomaha.org. 2. Department of Medicine-Nephrology, University of North Carolina, Chapel Hill, NC, USA. 3. Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA. 4. Division of Pediatric Nephrology and Hypertension, University of Tennessee Health Science Center, Memphis, TN, USA. 5. Pediatric Nephrology, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA. 6. Division of Pediatric Nephrology, Mayo Clinic, Rochester, MN, USA. 7. Division of Nephrology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. 8. Division of Nephrology, Helen DeVos Children's Hospital, Grand Rapids, MI, USA. 9. Kapi'olani Medical Center for Women and Children, Honolulu, HI, USA. 10. Department of Pediatrics, University of California Davis, Sacramento, CA, USA. 11. Division of Pediatric Nephrology and Hypertension, Atrium Health Levine Children's Hospital, Charlotte, NC, USA. 12. Vanderbilt University School of Medicine, Nashville, TN, USA. 13. Division of Pediatric Nephrology, Department of Pediatrics, University of Kentucky, Lexington, KY, USA. 14. University of Utah, Salt Lake City, UT, USA. 15. Pediatric Nephrology and Hypertension, Stony Brook Children's Hospital, Stony Brook, NY, USA. 16. Department of Pediatrics, Division of Pediatric Nephrology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. 17. Valley Children's Healthcare, Madera, CA, USA. 18. Nephrology Department, The Children's Medical Center, Dayton, OH, USA. 19. Department of Pediatric Nephrology, University of Minnesota, Minneapolis, MN, USA. 20. Children's Hospital of Georgia, Augusta University, Augusta, GA, USA. 21. Division of Nephrology, Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, OH, USA. 22. Division of Health Services and Outcomes Research, Children's Mercy Kansas City, Kansas City, MO, USA. 23. Division of Pediatric Nephrology, Children's Mercy Kansas City, Kansas City, MO, USA. 24. Departments of Internal Medicine and Pediatrics, Division of Nephrology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
Abstract
BACKGROUND: Eculizumab is approved for the treatment of atypical hemolytic uremic syndrome (aHUS). Its use off-label is frequently reported. The aim of this study was to describe the broader use and outcomes of a cohort of pediatric patients exposed to eculizumab. METHODS: A retrospective, cohort analysis was performed on the clinical and biomarker characteristics of eculizumab-exposed patients < 25 years of age seen across 21 centers of the Pediatric Nephrology Research Consortium. Patients were included if they received at least one dose of eculizumab between 2008 and 2015. Traditional summary statistics were applied to demographic and clinical data. RESULTS: A total of 152 patients were identified, mean age 9.1 (+/-6.8) years. Eculizumab was used "off-label" in 44% of cases. The most common diagnoses were aHUS (47.4%), Shiga toxin-producing Escherichia coli HUS (12%), unspecified thrombotic microangiopathies (9%), and glomerulonephritis (9%). Genetic testing was available for 60% of patients; 20% had gene variants. Dosing regimens were variable. Kidney outcomes tended to vary according to diagnosis. Infectious adverse events were the most common adverse event (33.5%). No cases of meningitis were reported. Nine patients died of noninfectious causes while on therapy. CONCLUSIONS: This multi-center retrospective cohort analysis indicates that a significant number of children and young adults are being exposed to C5 blockade for off-label indications. Dosing schedules were highly variable, limiting outcome conclusions. Attributable adverse events appeared to be low. Cohort mortality (6.6%) was not insignificant. Prospective studies in homogenous disease cohorts are needed to support the role of C5 blockade in kidney outcomes.
BACKGROUND: Eculizumab is approved for the treatment of atypical hemolytic uremic syndrome (aHUS). Its use off-label is frequently reported. The aim of this study was to describe the broader use and outcomes of a cohort of pediatric patients exposed to eculizumab. METHODS: A retrospective, cohort analysis was performed on the clinical and biomarker characteristics of eculizumab-exposed patients < 25 years of age seen across 21 centers of the Pediatric Nephrology Research Consortium. Patients were included if they received at least one dose of eculizumab between 2008 and 2015. Traditional summary statistics were applied to demographic and clinical data. RESULTS: A total of 152 patients were identified, mean age 9.1 (+/-6.8) years. Eculizumab was used "off-label" in 44% of cases. The most common diagnoses were aHUS (47.4%), Shiga toxin-producing Escherichia coli HUS (12%), unspecified thrombotic microangiopathies (9%), and glomerulonephritis (9%). Genetic testing was available for 60% of patients; 20% had gene variants. Dosing regimens were variable. Kidney outcomes tended to vary according to diagnosis. Infectious adverse events were the most common adverse event (33.5%). No cases of meningitis were reported. Nine patients died of noninfectious causes while on therapy. CONCLUSIONS: This multi-center retrospective cohort analysis indicates that a significant number of children and young adults are being exposed to C5 blockade for off-label indications. Dosing schedules were highly variable, limiting outcome conclusions. Attributable adverse events appeared to be low. Cohort mortality (6.6%) was not insignificant. Prospective studies in homogenous disease cohorts are needed to support the role of C5 blockade in kidney outcomes.
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