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Discontinuation of Eculizumab Maintenance Treatment for Atypical Hemolytic Uremic Syndrome

      To the Editor:
      Dr Ardissino and colleagues
      • Ardissino G.
      • Testa S.
      • Possenti I.
      • et al.
      Discontinuation of eculizumab maintenance treatment for atypical hemolytic uremic syndrome: a report of 10 cases.
      report successful discontinuation of eculizumab treatment in 7 of 10 patients with atypical hemolytic uremic syndrome (aHUS). This important report provides evidence that continued lifelong treatment may not be necessary in patients with aHUS, thus reducing side effects and costs. To ascertain generalizability and exclude selection bias, we should note the clinical characteristics of 12 patients who continued eculizumab treatment. Data presented in the first table of Ardissino et al
      • Ardissino G.
      • Testa S.
      • Possenti I.
      • et al.
      Discontinuation of eculizumab maintenance treatment for atypical hemolytic uremic syndrome: a report of 10 cases.
      suggest that discontinuing eculizumab treatment may be impossible in patients with a CFH mutation; in all 3 of these patients, treatment discontinuation was followed by recurrent disease that was evident within 6 weeks.
      We add data for eculizumab treatment discontinuation in patients with aHUS and a CFH mutation. To date, we have treated 4 such patients who were resistant to or dependent on treatment with plasmapheresis and received eculizumab in accordance with US Food and Drug Administration–proposed schedules. In our hospital, treatment is discontinued after 4 to 6 months if disease activity has disappeared and kidney function has improved and stabilized for at least 4 to 6 weeks. As shown in Table 1, eculizumab treatment was withdrawn in 3 of our patients, 2 of whom had no signs of disease activity as of their respective 11- and 17-month follow-ups. Recurrent disease developed in 1 patient 3 months after eculizumab therapy discontinuation. When comparing our patients with those of Ardissino et al,
      • Ardissino G.
      • Testa S.
      • Possenti I.
      • et al.
      Discontinuation of eculizumab maintenance treatment for atypical hemolytic uremic syndrome: a report of 10 cases.
      we noted a difference in the location of the CFH mutations, suggesting that patients with a mutation in exons 19 or 20 may be more prone to recurrence. Our data suggest that eculizumab therapy discontinuation is feasible in some patients with a CFH mutation. Future studies should evaluate the optimal treatment duration and risk of recurrence in relation to the patient’s underlying genetic lesion.
      Table 1Patient Characteristics and Eculizumab Treatment
      PatientSexAge at aHUS Onset (y)CFH MutationDuration of Eculizumab Treatment (mo)Follow-up After Discontinuing Eculizumab (mo)Outcome
      1F30p.Gln400Lys (exon 9)3517Stable, no recurrence
      2F21p.Trp858Arg (exon 17)4.53Recurrence, treatment restarted
      3F43p.Pro707Leu (exon 15)411Stable, no recurrence
      4F27p.Leu593* (exon 13)8
      At the time of writing, patient 4 was still receiving eculizumab.
      Not applicable
      At the time of writing, patient 4 was still receiving eculizumab.
      Stable, treatment at 3-wk intervals
      Abbreviations and definitions: *, premature stop codon; Arg, arginine; Gln, glutamine; Leu, leucine; Lys, lysine; p, protein; Pro, proline; Trp, tryptophan.
      a At the time of writing, patient 4 was still receiving eculizumab.

      Acknowledgements

      Financial Disclosure: Dr Wetzels has received a grant from Alexion, which markets eculizumab; Dr van de Kar is member of the Alexion International Advisory Board of aHUS.

      Reference

        • 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: 633-637

      Linked Article

      • Discontinuation of Eculizumab Maintenance Treatment for Atypical Hemolytic Uremic Syndrome: A Report of 10 Cases
        American Journal of Kidney DiseasesVol. 64Issue 4
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          Atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy, and as many as 70% of patients with aHUS have mutations in the genes encoding complement regulatory proteins. Eculizumab, a humanized recombinant monoclonal antibody targeting C5, has been used successfully in patients with aHUS since 2009. The standard maintenance treatment requires life-long eculizumab therapy, but the possibility of discontinuation has not yet been tested systematically. We report the safety of discontinuing eculizumab treatment in 10 patients who stopped treatment with the aim of minimizing the risk of adverse reactions, reducing the risk of meningitis, and improving quality of life while also reducing the considerable treatment costs.
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      • In Reply to ‘Discontinuation of Eculizumab Maintenance Treatment for Atypical Hemolytic Uremic Syndrome’
        American Journal of Kidney DiseasesVol. 65Issue 2
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          Drs Wetzels and van de Kar1 raise the issue of eculizumab treatment discontinuation in patients with atypical hemolytic uremic syndrome (aHUS) and a CFH mutation. As we described in our original article,2 patients treated with eculizumab for aHUS at our center were offered the opportunity to continue or discontinue maintenance treatment regardless of the underlying mutation (this issue was raised when stable remission of thrombotic microangiopathy and the serum creatinine nadir were reached). At this time, patients were provided with information to guide their decisions; of note, we informed patients that individuals with CFH and C3 gene mutations are more likely to experience relapse, and that relapse is more likely to be severe.
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