Incidence, management, and outcomes of autoimmune nephropathies following alemtuzumab treatment in patients with multiple sclerosis

Richard Phelps, Jonathan A. Winston, Daniel Wynn, Mario Habek, Hans Peter Hartung, Eva Kubala Havrdová, Glen S. Markowitz, David H. Margolin, Claudio E. Rodriguez, Darren P. Baker, Alasdair J. Coles

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Background: Autoimmune disorders including nephropathies have been reported more frequently in alemtuzumab-treated multiple sclerosis (MS) patients than in the general population. Objective: Describe instances of autoimmune nephropathy in alemtuzumab-treated MS patients. Methods: Cases were identified from safety monitoring within the alemtuzumab relapsing-remitting multiple sclerosis (RRMS) clinical development program (CDP) or post-marketing, or following off-label use. Results: As of 16 June 2017, 16 autoimmune nephropathies have occurred following alemtuzumab treatment for MS. The incidence of autoimmune nephropathies was 0.34% within the CDP (5/1485 patients). The five CDP cases (one of anti-glomerular basement membrane (anti-GBM) disease, two of membranous glomerulonephropathy, and two of serum anti-GBM antibody without typical anti-GBM disease) were identified early, responded to conventional therapy (where needed), and had favorable outcomes. Three of 11 cases outside the CDP occurred following off-label alemtuzumab use prior to approval for RRMS and were all anti-GBM disease. Diagnosis was delayed in one of these three cases and another did not receive appropriate treatment; all three cases resulted in end-stage renal failure. All anti-GBM disease cases with documented urinalysis demonstrated prior microscopic hematuria. Conclusion: Close monitoring of alemtuzumab-treated MS patients facilitates diagnosis and treatment early in the nephropathy course when preservation of renal function is more likely.

Original languageEnglish
Pages (from-to)1273-1288
Number of pages16
JournalMultiple Sclerosis Journal
Volume25
Issue number9
DOIs
StatePublished - 1 Aug 2019

Keywords

  • Alemtuzumab
  • anti-glomerular basement membrane disease
  • disease-modifying therapy
  • membranous glomerulonephropathy
  • multiple sclerosis
  • nephropathy

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