Discontinuation of Eculizumab in a Patient With Atypical Hemolytic Uremic Syndrome Due to a Mutation in CFH

Correspondence LETTER TO THE EDITOR Discontinuation of Eculizumab in a Patient With Atypical Hemolytic Uremic Syndrome Due to a Mutation in CFH To the Editor: Dr Ardissino and colleagues1,2 recently reported on 16 patients with atypical hemolytic uremic syndrome (aHUS) who discontinued eculizumab treatment: 5 patients experienced relapse and 11 patients remained in stable remission. None of the patients in remission had a mutation in CFH, the gene encoding complement factor H, while 3 of the 5 patients with relapse harbored a CFH mutation. In light of these data, the authors discouraged discontinuation of eculizumab therapy in patients with CFH mutations. In another recent publication, Wetzels et al3 reported 3 patients with aHUS due to CFH mutations and discontinuation of eculizumab, with 1 patient experiencing relapse. The authors hypothesized that the location of the mutation within CFH might be critical and that patients with mutations in short consensus repeat (SCR) 19 and 20 of the gene are more prone to relapse. We describe a young girl presenting with aHUS at the age of 21 months who was treated with 2 doses of eculizumab (Fig 1). Genetic analysis revealed a novel heterozygous mutation in SCR19 of CFH that is predicted to produce a truncated protein due to the introduction of a premature stop codon at amino acid 1155 (p.Gly1155*). Segregation analysis revealed that this mutation was also present in the child’s healthy mother. Eculizumab therapy was discontinued after 4 weeks, and the child has been in stable remission for 15 months. This case illustrates that it might be possible to discontinue eculizumab therapy in patients with mutations in the carboxyterminal portion of CFH if regular monitoring and careful

education of parents is done to ensure immediate reinitiation of therapy in case of relapse. Sandra Habbig, MD,1,2 Carsten Bergmann, MD3,4 Lutz T. Weber, MD1 1 University Children’s Hospital Cologne, Cologne, Germany 2 University of Cologne, Cologne, Germany 3 Bioscientia Center for Human Genetics, Ingelheim, Germany 4 University Freiburg Medical Center, Freiburg, Germany Corresponding author: [email protected]

Acknowledgments Support: None. Financial Disclosure: Dr Bergmann is an employee of Bioscientia and has previously been on a clinical advisory board sponsored by Alexion Pharmaceuticals, Inc, the manufacturer of eculizumab. Dr Weber is a member of the Scientific Advisory Board of Alexion Pharmaceuticals, Inc. Dr Habbig declares that she has no relevant financial interests.

References 1. Ardissino G, Possenti I, Tel F, et al. Discontinuation of eculizumab treatment in atypical hemolytic uremic syndrome: an update. Am J Kidney Dis. 2015;66(1):172-173. 2. Ardissino G, Testa S, Possenti I, et al. Discontinuation of eculizumab maintenance treatment for atypical hemolytic uremic syndrome: a report of 10 cases. Am J Kidney Dis. 2014;64(4): 633-637. 3. Wetzels JF, van de Kar NC. Discontinuation of eculizumab maintenance treatment for atypical hemolytic uremic syndrome [letter]. Am J Kidney Dis. 2015;65(2):342. Ó 2015 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2015.11.009

Figure 1. Prompt response to eculizumab treatment and stable remission after discontinuation of treatment in a patient with atypical hemolytic uremic syndrome due to a mutation in CFH, the gene encoding complement factor H. Abbreviation: LDH, lactate dehydrogenase.

Am J Kidney Dis. 2015;-(-):---

1