Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2014 Jun 17;82(24):2158-64.
doi: 10.1212/WNL.0000000000000520. Epub 2014 May 16.

Accelerated lymphocyte recovery after alemtuzumab does not predict multiple sclerosis activity

Onajite Kousin-Ezewu  1 , Laura Azzopardi  1 , Richard A Parker  1 , Orla Tuohy  1 , Alastair Compston  1 , Alasdair Coles  1 , Joanne Jones  2
Affiliations
Clinical Trial

Accelerated lymphocyte recovery after alemtuzumab does not predict multiple sclerosis activity

Onajite Kousin-Ezewu et al. Neurology. .

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Comparison of CD4+, CD8+, and CD19+ cell counts after each cycle of alemtuzumab in patients with and without on-study relapses
Patients were defined as having relapsed (shown in red) if they developed neurologic symptoms attributable to multiple sclerosis lasting >48 hours with an objective change in neurologic examination in the absence of infection. Cell units are ×109/L. Error bars indicate SD.
Figure 2
Figure 2. Comparison of CD4+, CD8+, and CD19+ cell counts after each cycle of alemtuzumab in patients with and without on-study active MRI scans
Patients were defined as having an active MRI scan (shown in red) if they had acquired new T2 lesions or enhancing lesions. Cell units are ×109/L. Error bars indicate SD.
Figure 3
Figure 3. Comparison of CD4+, CD8+, and CD19+ cell counts after each cycle of alemtuzumab in patients with and without acquisition of disability
Patients were deemed to have met the definition of sustained accumulation of disability if their Expanded Disability Status Scale increased by ≥1.5 points from a baseline of 0, or by ≥1.0 points from a baseline of ≥1.0. Patients meeting this definition are shown in red. Cell units are ×109/L. Error bars indicate SD.
See this image and copyright information in PMC

Comment in

References

    1. Coles AJ, Compston DA, Selmaj KW, et al. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med 2008;359:1786–1801 - PubMed
    1. Cohen JA, Coles AJ, Arnold DL, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet 2012;380:1819–1828 - PubMed
    1. Coles AJ, Twyman CL, Arnold DL, et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet 2012;380:1829–1839 - PubMed
    1. European Medicines Agency: EPAR summary for the public: Lemtrada (alemtuzumab). Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_.... Accessed November 22, 2013
    1. Hill-Cawthorne GA, Button T, Tuohy O, et al. Long term lymphocyte reconstitution after alemtuzumab treatment of multiple sclerosis. J Neurol Neurosurg Psychiatry 2012;83:298–304 - PubMed

Publication types

MeSH terms