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

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.

Ocrelizumab after natalizumab in JC-virus positive relapsing remitting multiple sclerosis patients

“…Since JCV carrier status is unlikely affected by switching to ocrelizumab, the decrease could reflect depletion of antibody producing cells induced by anti-CD20 therapy, although total IgG levels remained stable. A similar finding was previously reported in rituximab and fingolimod treatment, 10 yet others reported no significant changes during ocrelizumab treatment. 11 While awaiting future data, a low JCV index in MS patients treated with ocrelizumab should not necessarily be interpreted as JCV sero-negativity or a low PML risk category.…”

Anti-JCV antibody index does not change during ocrelizumab-treatment

“…In fingolimod-treated patients, a decrease in anti-JCV AI has been reported, which has been attributed to a decrease in numbers of circulating lymphocytes. 6 A decrease in anti-JCV AI and immunoglobulins has also been reported in rituximab-treated MS patients in a retrospective study. 7 This is in contrast to a retrospective assessment in ocrelizumab-treated MS patients, which described an increase in anti-JCV AI titers during ocrelizumab-treatment.…”

Risk Assessment of Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis Patients during 1 Year of Ocrelizumab Treatment

“…Although an anti-JCV antibody index is employed to assess PML risk also in course of other treatments, its usefulness is unproven. In fingolimod-treated patients, a decrease in anti-JCV antibody index has been reported, and it has been attributed to a decrease in numbers of circulating lymphocytes [ 53 ]. A decrease in anti-JCV antibody index and immunoglobulins has also been reported in MS patients treated with rituximab [ 37 ], in contrast with a retrospective study reporting an increase in anti-JCV antibody titers during ocrelizumab-treatment in MS patients [ 54 ].…”