Accelerated lymphocyte recovery after alemtuzumab does not predict multiple sclerosis activity

Neurology. 2014 Jun 17;82(24):2158-64. doi: 10.1212/WNL.0000000000000520. Epub 2014 May 16.

Abstract

Objective: To test the hypothesis that accelerated peripheral blood mononuclear cell recovery after alemtuzumab treatment of multiple sclerosis is associated with recurrent disease activity and to investigate the claim that CD4 counts greater than 388.5 × 10(6) cells/mL at 12 months can be used to identify patients who may benefit from further treatment.

Methods: A total of 108 patients were followed for a median of 99 months post alemtuzumab. Patients were classified as active or nonactive after each cycle of treatment based on clinical relapse, increasing disability, or new T2/enhancing MRI lesions. These outcomes were correlated with CD4, CD8, CD19, CD56+ NK, and monocyte counts.

Results: Of 108 patients, 56 (52%) relapsed at some point during follow-up. Mean annualized relapse rate after alemtuzumab was 0.17 vs 1.67 prior to treatment (equating to a 90% reduction). Of 108 patients, 28 (26%) met the criteria for sustained accumulation of disability. Median time to the lower limit of normal for CD19, CD8, and CD4 was 3, 19.5, and 32 months, respectively. There was no significant difference in the recovery of any cell population between patients with and without disease activity or accumulation of disability after treatment.

Conclusion: This study does not support the use of cell counts as biomarkers for identifying patients at greater risk of active disease following treatment with alemtuzumab.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Alemtuzumab
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antigens, CD / metabolism
  • Cell Count
  • Disability Evaluation
  • Female
  • Humans
  • Immunologic Factors / pharmacology*
  • Immunologic Factors / therapeutic use
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / pathology*
  • Outcome Assessment, Health Care
  • Secondary Prevention
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism
  • Time Factors
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • Antigens, CD
  • Immunologic Factors
  • Alemtuzumab