Successful discontinuation of eculizumab under immunosuppressive therapy in DEAP-HUS

Pediatr Nephrol. 2017 Jun;32(6):1081-1087. doi: 10.1007/s00467-017-3612-9. Epub 2017 Feb 20.

Abstract

Background: Deficiency of complement factor H-related plasma proteins and complement factor H autoantibody-positive hemolytic uremic syndrome (DEAP-HUS), which is characterized by the deficiency of complement-factor H-related (CFHR) plasma proteins and the subsequent formation of autoantibodies against complement factor H (CFH), has been reported to have an adverse outcome in one third of patients. Therapy options include prompt removal of antibodies by plasma exchange and immunosuppressive therapy. Recently, restoration of complement control using the monoclonal antibody eculizumab has been shown to be effective as first- and as second-line therapy in cases of therapy resistance or severe side effects of the applied therapy.

Diagnosis/treatment: Here, we report a 6-year-old girl with DEAP-HUS and first-line therapy with eculizumab under immunosuppressive therapy with glucocorticoids and mycophenolate mofetil (MMF). This therapy led to a prompt and sustained clinical recovery, to a stable reduction of complement activation, and to a rapid decline in autoantibody titer. A second increase in the autoantibody titer was successfully treated with methylprednisolone and the child remained in remission. After 8.3 months of sustained complement control and 4.5 months of stable antibody suppression, eculizumab was successfully discontinued without any sign of relapse.

Conclusions: To our knowledge, this is the first reported case of a child with DEAP-HUS treated with the combination of eculizumab and immunosuppression as first-line therapy avoiding any HUS- or therapy-related complications and resulting in prompt clinical recovery. Importantly, clinical remission is maintained after discontinuation of eculizumab under stable immunosuppression.

Keywords: Child; Complement activation; Renal failure; Thrombotic microangiopathy.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Autoantibodies / blood
  • Autoantibodies / immunology
  • Child
  • Complement Activation / drug effects*
  • Complement C3b Inactivator Proteins / metabolism*
  • Complement Factor H / immunology
  • Complement Factor H / metabolism
  • Drug Resistance
  • Drug Therapy, Combination
  • Female
  • Glucocorticoids / pharmacology
  • Glucocorticoids / therapeutic use
  • Hemolytic-Uremic Syndrome / blood
  • Hemolytic-Uremic Syndrome / immunology
  • Hemolytic-Uremic Syndrome / metabolism
  • Hemolytic-Uremic Syndrome / therapy*
  • Humans
  • Immunosuppression Therapy / methods
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use
  • Mycophenolic Acid / pharmacology
  • Mycophenolic Acid / therapeutic use
  • Plasma Exchange
  • Withholding Treatment

Substances

  • Antibodies, Monoclonal, Humanized
  • Autoantibodies
  • CFH protein, human
  • Complement C3b Inactivator Proteins
  • Glucocorticoids
  • Immunosuppressive Agents
  • Complement Factor H
  • eculizumab
  • Mycophenolic Acid