JCV STRATIFY (anti-JCV antibody) test has been utilized for more than decade to de-risk natalizumab treatment and other DMTs for risk of PML (Progressive Multifocal Leukoencephalopathy). Cases of PML have occurred predominantly in natalizumab, but less commonly with fingolimod (Gilenya), dimethylfumerate (Tecfidera) and rituximab.
A high JCV antibody index value indicates that the risk of developing PML is significantly raised. It is a test based around the antibodies that your own body produces against JCV either to prevent the primary infection or to keep control of the already present infection (JCV resides dormant in the brain, bone marrow and the kidney after infection).
So it is with great interest that I read the article by Farley et al. (see below for the abstract), who studied the influence of certain DMTs, namely rituximab, and fingolimod, and dimethylfumerate, on the JCV antibody index. With both rituximab and fingolimod there was a trend for a decrease in index values over time, but not dimethylfumerate (see Figure 1 below). They formulate that these rituximab and fingolimod may impair the the body’s antibody response to JCV. This effect was unrelated to the absolute reduction in lymphocyte counts that occurred on treatment, although we are not provided with data on the sub-types of lymphocytes involved i.e. CD4+ and CD8+ levels.
This of course a worrying development in the DMT saga, and in my mind further support for induction strategies, or other strategies that don’t rely on continuous immunosuppression for efficacy. Ocrelizumab with its hypogammaglobulinaemia (reduction in antibody levels) and nearly undetectable CD20+ B cells would also be a strong contender for this.
Surg Neurol Int. 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.
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.
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.
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.
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.