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. 2019 Apr 24:10:59.
doi: 10.25259/SNI-4-2019. eCollection 2019.

Anti-John Cunningham virus antibody index levels in multiple sclerosis patients treated with rituximab, fingolimod, and dimethyl fumarate

Stephen Farley  1 , Malcolm H Gottesman  2 , Sharon Friedman-Urevich  2 , Janin Ye  3 , Mark Shen  1 , Denise Grueneberg  2 , Lorraine Martone  2 , Rose Calixte  4
Affiliations

Anti-John Cunningham virus antibody index levels in multiple sclerosis patients treated with rituximab, fingolimod, and dimethyl fumarate

Stephen Farley et al. Surg Neurol Int. .

Abstract

Background: Progressive multifocal leukoencephalopathy (PML), a potentially fatal demyelinating disease caused by the John Cunningham virus (JCV), can occur as a complication of treatment with rituximab, fingolimod, and dimethyl fumarate. The primary objective of this study was to determine changes in anti-JCV antibody index values in multiple sclerosis (MS) patients treated with these three medications. Second, we explored the relationship between absolute lymphocyte count (ALC), anti-JCV antibody index values, and various patient characteristics.

Methods: In this retrospective chart review, we evaluated changes in JCV serology and ALC in 172 MS patients treated with fingolimod, rituximab, or dimethyl fumarate (2013-2016). Only those with known anti-JCV antibody and ALC values before starting the study medications were included. Subsequent values were obtained on an ad hoc basis throughout the study.

Results: There was a significant decrease in anti-JCV antibody index values in patients treated with fingolimod and rituximab (P = 0.03 and P = 0.014, respectively). A non-significant decreasing trend in anti-JCV antibody index values occurred in patients treated with dimethyl fumarate. Notably, there was no relationship between ALC and anti-JCV antibody index values for patients treated with rituximab, fingolimod, or dimethyl fumarate.

Conclusions: Anti-JCV antibody index values significantly decreased in MS patients treated with fingolimod and rituximab; however, this did not occur with dimethyl fumarate. Fingolimod and rituximab may impair the humoral response to the JCV. Nevertheless, a declining anti-JCV antibody index in MS patients treated with fingolimod or rituximab should not necessarily be interpreted as correlating with a decreased risk for PML.

Keywords: Anti-John Cunningham virus antibody index value; John Cunningham virus; dimethyl fumarate; fingolimod; lymphocyte count; multiple sclerosis; progressive multifocal leukoencephalopathy; rituximab.

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Conflict of interest statement

There are no conflicts of interest.

Figures

Figure 1:
Figure 1:
Changes in anti-JC index value with time.
Figure 2:
Figure 2:
Kaplan–Meier curve - time to lymphopenia Grade 1.
Figure 3:
Figure 3:
Kaplan–Meier curve - time to lymphopenia Grade 2.
Figure 4:
Figure 4:
Kaplan–Meier curve - time to lymphopenia Grade 3.
Figure 5:
Figure 5:
Kaplan–Meier curve - time to lymphopenia Grade 4.
See this image and copyright information in PMC

References

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