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.

Abstract Background: Patients with a compromised immune system are at risk for converting from latent tuberculosis infection (LTBI) to active tuberculosis infection. Multiple sclerosis (MS) therapies may put individuals with LTBI at higher risk of developing tuberculosis. Methods: Patients of the Beth Israel Deaconess Medical Center MS Center were screened for tuberculosis as part of routine testing with the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay from 2013 to 2017. Patients were tested either prior to or while on immunomodulating therapy. Results: 4 out of 222 patients (1.8%, 95% CI 0.1-3.6%) had positive QFT-GIT testing; 3 patients had risk factors for tuberculosis, having emigrated from TB endemic countries or worked in the health care industry. 28 out of 222 patients (12.6%) had an indeterminate assay result and 75.0% of these occurred in patients taking dimethyl fumarate (DMF). Fingolimod, natalizumab, or anti-CD20 treatments showed 0-7.7% indeterminate results. Conclusions: LTBI was seen at 1.8% prevalence in the Beth Israel Deaconess MS Center. Not all LTBI cases were associated with known risk factors for tuberculosis. Screening for LTBI prior to starting immunosuppressive agents for MS could help prevent activation of tuberculosis. DMF use is associated with indeterminate results in the QFT-GIT assay, possibly due to functional effects on lymphocytes and levels of cytokines, like interferon gamma. In contrast, fingolimod use was rarely associated with indeterminate QFT-GIT results in spite of a high rate of lymphopenia in virtually all cases.

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