Risk of serious infections in multiple sclerosis patients by disease course and disability status: Results from a Swedish register-based study

Brand, Judith S.; Smith, Kelsi A; Piehl, Fredrik; Olsson, Tomas; Montgomery, Scott

doi:10.1016/j.bbih.2022.100470

Cited by 16 publications

(22 citation statements)

References 35 publications

(48 reference statements)

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“…While female MS patients had a marginally increased overall incidence of infections, severe infections were instead relatively more frequent in males. This has also been previously reported 29,35,36 and could be explained either by a more aggressive MS course in male patients or by a greater male susceptibility to severe infections regardless of disability. In any case, neither DMTs nor age were associated with incidence of severe infections in our MS cohort (apart from a numerical increase in severe infections among patients on anti-CD20).…”

Section: Discussionsupporting

confidence: 81%

“…34 Somewhat similar to ours, a study based on the Swedish MS register observed that individuals with RRMS and low disability scores were at higher risk of infections as compared to controls, especially when DMTs were in place. 35 Furthermore, in the group of patients not receiving DMTs and with low disability, an increased risk of infection was only present in MS patients aged >60 years. 35 Taken together with our results, these findings suggest that the relative influence of DMTs on infection risk is particularly evident among younger MS patients, who are otherwise less likely to suffer from infections if immunosuppressive DMTs are not in place.…”

Section: Discussionmentioning

confidence: 97%

“…35 Furthermore, in the group of patients not receiving DMTs and with low disability, an increased risk of infection was only present in MS patients aged >60 years. 35 Taken together with our results, these findings suggest that the relative influence of DMTs on infection risk is particularly evident among younger MS patients, who are otherwise less likely to suffer from infections if immunosuppressive DMTs are not in place. The effect of DMTs is likely less evident among older patients, who carry a higher baseline risk of infections regardless of MS treatment.…”

Section: Discussionmentioning

confidence: 97%

“…First, despite being representative of the local MS population, the sample size is relatively small, especially as compared to national registries. 3,35 This prevented us from testing individual DMTs with infection risk, and potential differences are likely between DMTs that were grouped together in our study (e.g. between induction/pulsed DMTs such as cladribine and alemtuzumab and maintenance DMTs).…”

Section: Discussionmentioning

confidence: 99%

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Interplay between age and disease-modifying treatments in influencing infection risk in multiple sclerosis

Jacober,

Disanto,

Sacco

et al. 2023

Mult Scler

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Background: Disease-modifying treatments (DMTs) can increase the risk of infections in multiple sclerosis (MS). Aged individuals are usually excluded from clinical trials, and there is uncertainty regarding safety of immunosuppressive DMTs in these patients. Objective: To investigate the association of DMTs, ageing and other clinical variables with risk of infections in MS patients. Methods: Prospective single-centre observational study collecting information on occurrence, type and grade of infections in patients followed at the MS centre, Lugano (Switzerland). Associations with infection risk were tested using multivariable Poisson and Cox regressions. Results: A total of 503 patients were included (injectables/untreated, n = 127; orals, n = 139; monoclonal antibodies (MAB), n = 237) and 326 infections recorded over 12.6 (11.6–14.0) months. As compared to injectable DMTs/no treatment, MAB and oral DMTs were positively associated with infection incidence (IRR = 2.32, 95% confidence interval (CI) = 1.39–3.89, p = 0.001; IRR = 2.04, 95% CI = 1.19–3.49, p = 0.009, respectively). After excluding COVID-19, the effect of MAB was stronger among patients <50 years (IRR = 5.90, 95% CI = 2.80–12.45, p < 0.001) than >50 years (IRR = 1.95, 95% CI = 0.91–4.15, p = 0.084). Higher disability and male sex were the only variables associated with severe infections. Conclusion: Treatment with MAB and oral DMTs is associated with higher incidence of infections, with a stronger effect in young MS patients. Disability appears the main predictor of severe infections regardless of treatment.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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Interplay between age and disease-modifying treatments in influencing infection risk in multiple sclerosis

Jacober,

Disanto,

Sacco

et al. 2023

Mult Scler

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“…However, it is still unclear whether these 2 variables are independently associated with severe COVID-19 or whether the association depends on MS phenotype. Progressive MS (PMS), including primary or secondary PMS, is associated with a higher risk of severe infection . Patients with PMS also have a higher likelihood of being hospitalized for COVID-19 compared with those with relapsing-remitting MS (RRMS) .…”

Section: Introductionmentioning

confidence: 99%

Association Between Anti-CD20 Therapies and COVID-19 Severity Among Patients With Relapsing-Remitting and Progressive Multiple Sclerosis

et al. 2023

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ImportanceIn patients with multiple sclerosis (MS), factors associated with severe COVID-19 include anti-CD20 therapies and neurologic disability, but it is still unclear whether these 2 variables are independently associated with severe COVID-19 or whether the association depends on MS clinical course.ObjectiveTo assess the association between anti-CD20 therapies and COVID-19 severity in patients with relapsing-remitting MS (RRMS) and progressive MS (PMS).Design, Setting, and ParticipantsThis multicenter, retrospective cohort study used data from the COVISEP study, which included patients with MS and COVID-19 from February 1, 2020, to June 30, 2022, at 46 French MS expert centers, general hospitals, and private neurology practices. Eligible patients with RRMS were those treated with high-efficacy MS therapy (ie, anti-CD20, fingolimod, or natalizumab), and eligible patients with PMS were those younger than 70 years with an Expanded Disability Status Scale (EDSS) score of 8 or lower. Patients were monitored from COVID-19 symptom onset until recovery or death.ExposuresCurrent anti-CD20 therapy (ocrelizumab or rituximab).Main Outcomes and MeasuresThe main outcome was severe COVID-19 (ie, hospitalization with any mode of oxygenation or death). All analyses were conducted separately in patients with RRMS and PMS using propensity score–weighted logistic regression. Subgroup analyses were performed according to COVID-19 vaccine status, sex, EDSS score, and age.ResultsA total of 1400 patients, 971 with RRMS (median age, 39.14 years [IQR, 31.38-46.80 years]; 737 [76.1%] female) and 429 with PMS (median age, 54.21 years [IQR, 48.42-60.14 years]; 250 [58.3%] female) were included in the study. A total of 418 patients with RRMS (43.0%) and 226 with PMS (52.7%) were treated with anti-CD20 therapies. In weighted analysis, 13.4% and 2.9% of patients with RRMS treated and not treated with anti-CD20 had severe COVID-19, respectively, and anti-CD20 treatment was associated with increased risk of severe COVID-19 (odds ratio [OR], 5.20; 95% CI, 2.78-9.71); this association persisted among vaccinated patients (7.0% vs 0.9%; OR, 8.85; 95% CI, 1.26-62.12). Among patients with PMS, 19.0% and 15.5% of patients treated and not treated with anti-CD20 had severe COVID-19, respectively, and there was no association between anti-CD20 treatment and severe COVID-19 (OR, 1.28; 95% CI, 0.76-2.16). In PMS subgroup analysis, anti-CD20 exposure interacted negatively with EDSS score (P = .009 for interaction) and age (P = .03 for interaction); anti-CD20 therapies were associated with risk of severe COVID-19 only in patients with less neurologic disability and younger patients with PMS.Conclusions and RelevanceIn this cohort study, risk of severe COVID-19 was higher in patients with PMS than in those with RRMS. Use of anti-CD20 therapies was associated with an increased risk of severe COVID-19 among patients with RRMS. In patients with PMS, there was no association between anti-CD20 therapies and risk of severe COVID-19.

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De-escalation and Discontinuation of Disease-Modifying Therapies in Multiple Sclerosis

Gross,

Corboy

2024

Curr Neurol Neurosci Rep

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Risk of serious infections in multiple sclerosis patients by disease course and disability status: Results from a Swedish register-based study

Cited by 16 publications

References 35 publications

Interplay between age and disease-modifying treatments in influencing infection risk in multiple sclerosis

Interplay between age and disease-modifying treatments in influencing infection risk in multiple sclerosis

Association Between Anti-CD20 Therapies and COVID-19 Severity Among Patients With Relapsing-Remitting and Progressive Multiple Sclerosis

De-escalation and Discontinuation of Disease-Modifying Therapies in Multiple Sclerosis

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