Effects of disease-modifying therapy on peripheral leukocytes in patients with multiple sclerosis

Schweitzer, Finja; Laurent, Sarah; Fink, Gereon R.; Barnett, Michael; Hartung, Hans‐Peter; Warnke, Clemens

doi:10.1007/s00415-019-09690-6

Cited by 35 publications

(32 citation statements)

References 73 publications

(70 reference statements)

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“…However, the use of herpes antivirals was lower with rituximab compared to fingolimod and natalizumab; ocrelizumab clinical trials reported an increased risk of respiratory tract infections, 17,18 and safety issues emerged in diseases other than MS 19 . With respect to the association with treatment duration, it has been shown that long‐term anti‐CD20 treatment is associated with the risk of hypogammaglobulinemia in neuromyelitis optica‐spectrum disorder 20 . A protracted treatment may impact on the protective, anti–SARS‐CoV‐2 humoral response 21 and on a pre‐existing humoral and cellular immune repertoire, recently described in unexposed individuals 22,23 …”

Section: Discussionmentioning

confidence: 99%

“…This preliminary result needs to be confirmed, but it is consistent with the idea that the immunological effects of ocrelizumab may last longer than 6 months. Reducing the frequency of dosing, or adjusting it according to the monitoring of B‐cell repopulation kinetics in individual patients, 20 may maintain efficacy while limiting the risk of infection 24 . A similar strategy deserves attention also in view of future vaccinations 25 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Disease‐Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Patti

Nozzolillo²,

Bellacosa³

et al. 2021

Annals of Neurology

408

481

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Objective This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID‐19) in people with multiple sclerosis (PwMS). Methods We retrospectively collected data of PwMS with suspected or confirmed COVID‐19. All the patients had complete follow‐up to death or recovery. Severe COVID‐19 was defined by a 3‐level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID‐19 by multivariate and propensity score (PS)‐weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID‐19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty‐eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti‐CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18–4.74, p = 0.015) with increased risk of severe COVID‐19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20–12.53, p = 0.001). Results were confirmed by the PS‐weighted analysis and by all the sensitivity analyses. Interpretation This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID‐19 pandemic persists. ANN NEUROL 2021;89:780–789

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Disease‐Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Patti

Nozzolillo²,

Bellacosa³

et al. 2021

Annals of Neurology

408

481

View full text Add to dashboard Cite

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“…In this regard, prophylactic acyclovir therapy is recommended in patients experiencing a grade IV lymphopenia following CLAD. 29 As antibodies contribute to maintain protection from pathogens, inhibition of (intrathecal) antibody production is of special interest in the pathomechanisms involved in MS, where oligoclonal bands (OCBs) represent a hallmark. In fact, injectable CLAD was found to eliminate OCBs in 55% of pwMS, which in turn correlated with better clinical outcome.…”

Section: Discussionmentioning

confidence: 99%

“…These kinetics suggest that patients receiving CLAD may be more prone to viral infections within the first 9 month of administration, which should be considered for clinical purposes. In this regard, prophylactic acyclovir therapy is recommended in patients experiencing a grade IV lymphopenia following CLAD 29 . As antibodies contribute to maintain protection from pathogens, inhibition of (intrathecal) antibody production is of special interest in the pathomechanisms involved in MS, where oligoclonal bands (OCBs) represent a hallmark.…”

Section: Discussionmentioning

confidence: 99%

Long‐term peripheral immune cell profiling reveals further targets of oral cladribine in MS

Moser

Schwenker

Seiberl

et al. 2020

Ann Clin Transl Neurol

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Objectives: To expand the knowledge about the immunological consequences of cladribine (CLAD), a pulsed immune reconstitution therapy approved for active multiple sclerosis (MS), beyond the known short-term effects on peripheral immune cell subsets. Methods: In this study, we characterized depletion and restitution kinetics as well as cytokine profiles of peripheral immune cell subsets in 18 patients with MS following treatment with oral CLAD. The methods involved blood collection prior to CLAD and every three months over a period of 24 months, and extensive characterization of various immune cells subsets by multiparametric flow cytometry. Results: We found a selectivity of CLAD towards central memory T cells and memory B cells and detected a hyper-repopulation of maturing B cells. Counts of classical (À65%) and various nonclassical TH17 cells (À84% to À87%) were markedly reduced 24 months after treatment start, and were comparable with depletion rates of classswitched memory B-cell phenotypes (À87% to À95%). The nadir of TH cells was more pronounced in the second treatment year. We observed a proportional surge of CD20 T-cell subsets and an expansion of regulatory T, B and NK cells. Natural killer T cells (NKT) were only depleted in year two and did not recover. Interpretation: Peripheral immune cell profiling revealed more differentiated insights into the immunological effects of CLAD. While some immune cell subsets expanded, we also observed additive depleting effects after the second treatment course. Further studies are required to elucidate whether these changes are paramount for the consistent and prolonged disease-modifying effect of CLAD.

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“…Upon using cladribine for more than 4 months, a relevant decrease in circulating CD4 + T, NK cells, B cells, and T cells resulting in lymphopenia which makes COVID-19 patients more susceptible to infection severity and secondary infection. [44][45][46][47] The observed relevant immunosuppression actions following cladribine administration are mainly associated with higher infectious risk. [46,47] Several studies also suggest that cladribine treatments can be initiated in COVID-19 patients with demandable general health monitoring, but the risk-to-benefit ratio should be taken into consideration especially for aged immunocompromised patients.…”

Section: The Impact Of Immunotherapies In Managing Neurological Manifmentioning

confidence: 99%

Immunotherapies and COVID-19 related Neurological manifestations: A Comprehensive Review Article

Anwar

2020

Journal of Immunoassay and Immunochemistry

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In December 2019, an outbreak of pandemic severe respiratory distress syndrome coronavirus disease 2019 (COVID-19) initially occurred in China, has spread the world resulted in serious threats to human public health. Uncommon neurological manifestations with pathophysiological symptoms were observed in infected patients including headache, seizures, and neuroimmunological disorders. Regardless of whether these neurological symptoms are direct or indirect casual infection relationship, this novel viral infection has a relevant impact on the neuroimmune system that requires a neurologist's careful assessment. Recently, the use of immunotherapy has been emerged in fighting against COVID-19 infection despite the uncertain efficiency in managing COVID-19 related disorders or even its proven failure by increasing its severity. Herein, the author is addressing the first approaches in using immunotherapies in controlling COVID-19 viral impact on the brain by highlighting their role in decreasing or increasing infection risks among subjects. This point of view review article supports the use of immunotherapies in managing COVID-19 neurological disorders but in optimal timing and duration to ensure the maximum therapeutic outcome by reducing morbidity and mortality rate. Based on recently published data, the current review article highlights the beneficial effects and drawbacks of using immunotherapies to combat COVID-19 and its neurological symptoms.

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Effects of disease-modifying therapy on peripheral leukocytes in patients with multiple sclerosis

Cited by 35 publications

References 73 publications

Disease‐Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Disease‐Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Long‐term peripheral immune cell profiling reveals further targets of oral cladribine in MS

Immunotherapies and COVID-19 related Neurological manifestations: A Comprehensive Review Article

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