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

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)1352458519841829
JournalMultiple Sclerosis Journal
Early online date15 Apr 2019
DOIs
Publication statusE-pub ahead of print - 15 Apr 2019

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