Infections in Patients Receiving Multiple Sclerosis Disease-Modifying Therapies

Abstract

Aside from glatiramer acetate and interferon-beta therapies, all other multiple sclerosis treatments to various degrees impair immune surveillance and may predispose patients to the development of both community-acquired and opportunistic infections. Some of these infections are rarely seen in neurologic practice, and neurologists should be aware of how to monitor for these infections and how to educate patients about medication-specific risks. Of particular interest in this discussion is the risk of PML in association with the recently approved B cell depleting therapy, ocrelizumab, particularly when switching from natalizumab. The risk of infection in association with MS treatments has become one of the most important factors in the choice of therapy. Balance of the overall risk versus benefit should be continuously re-evaluated during treatment.

Impact of the COVID-19 pandemic on the health care of >1,000 People living with multiple sclerosis: A cross-sectional study

“…A quarter of these participants made the decision without the input of their neurologist. Although it is plausible that high efficacy therapies confer risk of worse outcomes in COVID-19, (Wijnands et al, 2018 Oct;Grebenciucova and Pruitt, 2017;Luna et al, 2020) not all data demonstrate as negative of a prognosis as first may have been feared (Meca-Lallana et al, 2020;Hsu et al, 2020;Mathies et al, 2020;Zhu et al, 2020;Novi et al, 2020). Some authors have posited that immunosuppression is protective due to the inflammatory nature of the SARS-CoV2 infection.…”

The TCR Repertoire Reconstitution in Multiple Sclerosis: Comparing One-Shot and Continuous Immunosuppressive Therapies

“…CD8+ naive repertoire diversity is commonly higher compared to memory (CM, EM, and TEMRA) CD8+ subpopulations (41), and it represents, along with crossreactivity, the major strategy adopted by the immune system to face a great variety of antigens (42). Natalizumab has been shown to reduce immune surveillance modulating immune cell populations and subpopulations (43)(44)(45). Therefore, the reduced TCR diversity of CD8+ naive cells in our NTZ repertoires may reflect decreased immune protection.…”

COVID-19 and MS disease-modifying therapies

“…Second, many DMTs confer their benefit in MS by limiting aspects of the immune response, which could, in theory, allow for greater viral replication and potentially worse infection. 11 This same DMT effect may actually be beneficial by limiting the overly aggressive immune response occasioned by SARS-CoV-2 infection, which is thought to underlie its severe complications. Third, a substantial number of individuals with MS are older than 60 years, a population with a demonstrated increased risk of severe morbidity and mortality from COVID-19.…”

“…e11,e12 Although there appears to be no association between overall infection and the degree of lymphopenia in DMF-treated patients, e11 , the occurrence of PML with DMF has largely, although not exclusively, occurred with lymphocyte counts below 500 cells/mm 3 sustained for >6 months in JCV antibody index seropositive individuals. 11 Dimethyl fumarate blocks proinflammatory cytokine production e13 and can inhibit macrophage function in vitro, thereby suppressing inflammation. e14 Furthermore, DMF has been demonstrated to ameliorate lung fibrosis in pulmonary arterial hypertension.…”