Anti-JC virus antibody index changes in rituximab-treated multiple sclerosis patients

Abstract

Rituximab, a monoclonal antibody to CD20, is an effective treatment for relapsing remitting multiple sclerosis (MS) reducing relapse rate by at least 50% over time. Although the mechanism for this clinical benefit is unclear, rituximab depletes circulating B cells, which can perform antigen presentation and stimulation of T cells. Another anti-CD20 drug, ocrelizumab, has recently been FDA approved to treat both relapsing remitting and progressive forms of MS. While long-term effects of ocrelizumab use are essentially unknown, long-term use of rituximab has been associated with the development of progressive multifocal leukoencephalopathy (PML) at an incidence of approximately 1/25,000 in non-MS conditions. Serostatus for JC virus (JCV), the causative agent for PML, is an important risk stratification tool for natalizumab, but its utility in other MS treatments is uncertain. We found that rituximab use was associated with a reduction in JCV antibody index values in MS patients. Reductions in immunoglobulins, IgM in particular, are seen in concert with JCV antibody reductions. Physicians should exercise caution when using JCV antibody indices to assess any risk of PML for patients on rituximab.

Reduced serum immunoglobulin G concentrations in multiple sclerosis: prevalence and association with disease-modifying therapy and disease course

“…15 In addition to predisposing to infections, another clinical implication of low serum IgG concentrations is false-negative antibody testing during rituximab therapy, which was reported recently. 17 During rituximab therapy, not only IgG concentrations but also the JCV antibody index decreased. 17 Since reduced serum IgG concentrations may lead to false-negative JCV antibody index test results in patients treated with anti-CD20 therapies, this assay must be interpreted cautiously when assessing PML risk, for example, when planning to switch from anti-CD20 therapies to natalizumab.…”

“…17 During rituximab therapy, not only IgG concentrations but also the JCV antibody index decreased. 17 Since reduced serum IgG concentrations may lead to false-negative JCV antibody index test results in patients treated with anti-CD20 therapies, this assay must be interpreted cautiously when assessing PML risk, for example, when planning to switch from anti-CD20 therapies to natalizumab.…”

“…16 Furthermore, reduced serum IgG concentrations may interfere with standard serological testing as the John Cunningham virus (JCV) antibody index decreased alongside IgG concentrations in patients treated with rituximab. 17…”

Treatment Optimization in Multiple Sclerosis: Canadian MS Working Group Recommendations

“…Index values may be altered by anti-CD20 agents and results should be interpreted with caution. 186 It is not known if switching from natalizumab to another high-efficacy DMT increases the risk of PML. A concern is the reported occurrence of carryover cases of PML after sequential DMTs.…”

<p>Rituximab Prevents the Development of Experimental Autoimmune Encephalomyelitis (EAE): Comparison with Prophylactic, Therapeutic or Combinational Regimens</p>

“…12 Intrathecal administration of RTX in progressive MS was well tolerated, 13 demonstrating good tolerability and efficacy in cases of both relapsing and progressive forms of MS. 14 The risk of John Cunningham (JC) virus and progressive multifocal leukoencephalopathy (PML) in MS patients was lowest in RTX-treated MS patients as compared to natalizumab, fingolimod or other diseasemodifying therapy (DMT). 15,16 In this work, we systematically investigated the effects of RTX on ameliorating EAE disorder. We utilized several treatment regimens, including prophylactic treatment using the drug orally or intraperitoneally, as well as using it as a therapeutic agent.…”