Risk of invasive fungal infections among patients treated with disease modifying treatments for multiple sclerosis: a comprehensive review

Scotto, Riccardo; Reia, Antonio; Buonomo, Antonio Riccardo; Moccia, Marcello; Viceconte, Giulio; Pisano, Elisabetta; Zappulo, Emanuela; Morra, Vincenzo Brescia; Gentile, Ivan

doi:10.1080/14740338.2021.1918673

Cited by 13 publications

(10 citation statements)

References 98 publications

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“…Of note, highly active DMTs ideally cause more common and severe side effects than platform treatments, 2 but, in this study, did not reflect on the risk of emergency hospital admissions, suggesting appropriate management. 31 Overall, these findings suggest that well-staffed MS units and appropriate use of DMTs (i.e. prescription and adherence monitoring) can reduce the risk of emergency admissions, with subsequent reduction of medical and societal costs.…”

Section: Discussionmentioning

confidence: 76%

Emergency medical care for multiple sclerosis: A five-year population study in the Campania Region (South Italy)

Moccia

Affinito

Ronga³

et al. 2022

Mult Scler

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Background: Emergency hospital admissions are common in multiple sclerosis (MS), and can highlight unmet medical needs. Objectives: To evaluate burden, predictors and outcomes of MS emergency admissions. Methods: This is a population-based study, conducted in the Campania Region (South Italy) from 2015 to 2019, using hospital discharge records, drug prescriptions and outpatients. The risk of emergency hospital admissions and the likelihood of worse outcomes were evaluated using the Cox regression and multinomial logistic regression models, respectively, in relation to age, sex, disease-modifying treatments (DMTs), comorbidities and adherence. Results: We recorded 1225 emergency admissions for 1001 patients (out of 5765 prevalent MS patients), overall costing 4,143,764.67 EUR. The risk of emergency admissions increased with age (hazard ratio (HR) = 1.02; 95% confidence interval (CI) = 1.01, 1.03; p < 0.01) and comorbidities (HR = 1.62; p < 0.01), and decreased in patients using DMTs (interferon beta/peg-interferon beta/glatiramer acetate HR = 0.19; p < 0.01; teriflunomide/dimethyl-fumarate/fingolimod HR = 0.18; p < 0.01, and alemtuzumab/cladribine/natalizumab/ocrelizumab HR = 0.21; p < 0.01), and with higher adherence (HR = 0.18; 95% CI = 0.13, 0.26; p < 0.01). Following emergency admission, older age was associated with probability of death ( n = 63) (odds ratio (OR) = 1.06; p < 0.01) and discharge to long-term facility ( n = 65) (OR = 1.03; p = 0.01). Conclusion: With 17% people with MS requiring emergency medical care over 5 years, improved management of DMTs and comorbidities could potentially reduce their medical, social and financial burden.

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Section: Discussionmentioning

confidence: 76%

Emergency medical care for multiple sclerosis: A five-year population study in the Campania Region (South Italy)

Moccia

Affinito

Ronga³

et al. 2022

Mult Scler

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“…Another patient developed PML with only minor sequela from that. Other opportunistic infections can occur during NTZ treatment, but must be considered rare ( 16 ). Such were not seen in our cohort.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of Natalizumab in Achieving No Evidence of Disease Activity (NEDA-3)—Data From a Local Norwegian Cohort

2021

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Objective: We aimed to determine the effectiveness of natalizumab (NTZ) by assessing overall No Evidence of Disease Activity 3 (NEDA-3) in a local Norwegian cohort.Background: NTZ is an immunomodulating drug used in the treatment of multiple sclerosis (MS). It has typically been used as a second-line treatment, but certain patients with high disease activity have started directly with NTZ.Methods: This retrospective cohort study includes all patients who received NTZ for relapsing–remitting MS at Nordland Hospital in the period 2008–2018. In June 2019, status for every patient was assessed, and a survival curve was used to show the cumulative probability of achieving NEDA-3 over time.Results: The cohort consisted of 66 patients, 49 women and 17 men with a mean age of 40.0 ± 10.8 years. Each patient received on average 45.8 ± 36.4 NTZ infusions. Mean age and Expanded Disability Status Scale (EDSS) at first infusion was 34.8 ± 10.5 and 3.2 ± 1.9, respectively. Prior to NTZ treatment, 83% had used other disease modulating drugs and 65% were anti-JC virus (JCV) seronegative. During the study period, seven patients converted to seropositive. In 2019, 40 patients had switched or stopped treatment: 19 due to positive JCV serostatus, 9 due to disease activity, 7 due to adverse effects or complications (1 progressive multifocal leukoencephalopathy), 2 due to pregnancy, and 3 due to autologous hematopoietic cell transplantation abroad. Three patients experienced rebound in the wake of discontinuation (7.5%). Of the patients receiving NTZ for more than 3 years (n = 33), 50% had achieved NEDA-3 after 3 years. Compared to those with evidence of disease activity (EDA), these NEDA-3 patients had significant lower EDSS score before first NTZ treatment (p = 0.04). They were also slightly, but not significantly, younger at debut of their MS, at the diagnosis and at first NTZ treatment. Of all the patients who ever started on NTZ, 23% had achieved NEDA-3 5 years later. The mean EDSS in 2019 was 3.6 ± 2.5.Conclusion: Despite the high rate of treatment switch, mainly due to the risk of PML, almost one in four who started on NTZ achieved NEDA-3 after 5 years, and the overall disease progression was low in the total cohort. Treating less advanced disease seems to predict better long-term stability.

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“…Other opportunistic infections increasing with age can be cryptococcal meningitis and herpes encephalitis (fingolimod, natalizumab) (318,319), mucocutaneous herpes infection [sphingosine-1-phosphate receptor modulators, natalizumab, alemtuzumab], and varicella-zoster reactivation [sphingosine-1-phosphate receptor modulators, dimethyl fumarate (320), natalizumab, cladribine, alemtuzumab, ocrelizumab], human papilloma virus (fingolimod), and Listeria meningitis (alemtuzumab) [reviewed by (310,321)].…”

Section: Efficacy and Safety Of Disease Modifying Therapies In Aging ...mentioning

confidence: 99%

Molecular Mechanisms of Immunosenescene and Inflammaging: Relevance to the Immunopathogenesis and Treatment of Multiple Sclerosis

Perdaens

Pesch

2022

Front. Neurol.

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Aging is characterized, amongst other features, by a complex process of cellular senescence involving both innate and adaptive immunity, called immunosenescence and associated to inflammaging, a low-grade chronic inflammation. Both processes fuel each other and partially explain increasing incidence of cancers, infections, age-related autoimmunity, and vascular disease as well as a reduced response to vaccination. Multiple sclerosis (MS) is a lifelong disease, for which considerable progress in disease-modifying therapies (DMTs) and management has improved long-term survival. However, disability progression, increasing with age and disease duration, remains. Neurologists are now involved in caring for elderly MS patients, with increasing comorbidities. Aging of the immune system therefore has relevant implications for MS pathogenesis, response to DMTs and the risks mediated by these treatments. We propose to review current evidence regarding markers and molecular mechanisms of immunosenescence and their relevance to understanding MS pathogenesis. We will focus on age-related changes in the innate and adaptive immune system in MS and other auto-immune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. The consequences of these immune changes on MS pathology, in interaction with the intrinsic aging process of central nervous system resident cells will be discussed. Finally, the impact of immunosenescence on disease evolution and on the safety and efficacy of current DMTs will be presented.

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Risk of invasive fungal infections among patients treated with disease modifying treatments for multiple sclerosis: a comprehensive review

Cited by 13 publications

References 98 publications

Emergency medical care for multiple sclerosis: A five-year population study in the Campania Region (South Italy)

Emergency medical care for multiple sclerosis: A five-year population study in the Campania Region (South Italy)

Effectiveness of Natalizumab in Achieving No Evidence of Disease Activity (NEDA-3)—Data From a Local Norwegian Cohort

Molecular Mechanisms of Immunosenescene and Inflammaging: Relevance to the Immunopathogenesis and Treatment of Multiple Sclerosis

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