Mortality and cause of death in multiple sclerosis in western Norway 1950–2021: a registry-based linkage study

Willumsen, Johannes Sverre; Grytten, Nina; Aarseth, Jan Harald; Myklebust, Tor Åge; Myhr, Kjell–Morten; Midgard, Rune

doi:10.1136/jnnp-2022-329169

Cited by 10 publications

(18 citation statements)

References 32 publications

(72 reference statements)

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“…Multiple sclerosis (MS) mortality rates calculated from large population-based registries in Europe and North America have estimated that people with MS (PwMS) have a life expectancy 6–14 years less than the general population and a mortality risk 2–3 times higher 1–6. Few mortality data from the southern hemisphere exist and the last nationwide Australian mortality study was published in 1989 7.…”

Section: Introductionmentioning

confidence: 99%

“…Mortality outcomes have been difficult to compare between studies due to differing methodology and background populations 8. Recent studies have used a combination of classic survival analyses (Kaplan-Meier curves and Cox regression) with SMRs as well as excess death rates (EDRs) 1–6 8–10…”

Section: Introductionmentioning

confidence: 99%

“…Overall, studies indicate that mortality rates have decreased and life expectancy of PwMS has increased relative to, but not as yet reaching, the levels of the general population 4 6 10 11. Several key factors have been associated with a higher mortality risk and shorter survival.…”

Section: Introductionmentioning

confidence: 99%

“…Several key factors have been associated with a higher mortality risk and shorter survival. Those with a younger age of onset have shorter survival from birth compared with older onset PwMS and a higher mortality risk compared with the general population 3 4 6 10. Progressive-onset disease has been found to be a negative prognostic factor in most studies, but one recent paper reported a similar survival age for relapsing remitting MS and primary progressive MS 3 6 12.…”

Section: Introductionmentioning

confidence: 99%

“…Those with a younger age of onset have shorter survival from birth compared with older onset PwMS and a higher mortality risk compared with the general population 3 4 6 10. Progressive-onset disease has been found to be a negative prognostic factor in most studies, but one recent paper reported a similar survival age for relapsing remitting MS and primary progressive MS 3 6 12. There have been conflicting reports on the impact of sex on MS survival, complicated by changing sex ratios in MS over time 8.…”

Section: Introductionmentioning

confidence: 99%

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Multiple sclerosis mortality in New Zealand: a nationwide prospective study

Leadbetter

MacAskill

Myall

et al. 2023

J Neurol Neurosurg Psychiatry

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BackgroundMortality data from Europe and North America show a shorter life expectancy for people with multiple sclerosis (MS). It is not known if a similar mortality risk exists in the southern hemisphere. We analysed the mortality outcomes of a comprehensive New Zealand (NZ) MS cohort, 15 years postrecruitment.MethodsAll participants of the nationwide 2006 NZ MS prevalence study were included and mortality outcomes were compared with life table data from the NZ population using classic survival analyses, standardised mortality ratios (SMRs) and excess death rates (EDRs).ResultsOf 2909 MS participants, 844 (29%) were deceased at the end of the 15-year study period. Median survival age for the MS cohort was 79.4 years (78.5, 80.3), compared with 86.6 years (85.5, 87.7) for the age-matched and sex-matched NZ population. The overall SMR was 1.9 (1.8, 2.1)). Symptom onset between 21 and 30 years corresponded to an SMR of 2.8 and a median survival age 9.8 years lower than the NZ population. Progressive-onset disease was associated with a survival gap of 9 years compared with 5.7 years for relapsing onset. The EDR for those diagnosed in 1997–2006 was 3.2 (2.6, 3.9) compared with 7.8 (5.8, 10.3) for those diagnosed between 1967 and 1976.ConclusionsNew Zealanders with MS have a median survival age 7.2 years lower than the general population and twice the mortality risk. The survival gap was greater for progressive-onset disease and for those with an early age of onset.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Multiple sclerosis mortality in New Zealand: a nationwide prospective study

Leadbetter

MacAskill

Myall

et al. 2023

J Neurol Neurosurg Psychiatry

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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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Narrative Review on the Use of Cladribine Tablets as Exit Therapy for Stable Elderly Patients with Multiple Sclerosis

de Seze,

Dive,

Ayrignac

et al. 2024

Neurol Ther

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The number of ageing people with relapsing multiple sclerosis (RMS) is increasing. The efficacy of disease-modifying therapies (DMTs) for RMS declines with age. Also, older persons with MS may be more susceptible to infections, hospitalisations and malignancy. Aging people with MS have higher rates of comorbidities versus aged-matched controls, increasing the individual risk of disability. We review the therapeutic properties of cladribine tablets (CladT) in ageing people with RMS, with regard to their utility for allowing these individuals to cease continuous administration of a DMT (i.e. to act as an “exit therapy”). CladT is thought to be an immune reconstitution therapy, in that two short courses of oral treatment 1 year apart provide suppression of MS disease activity in responders that far outlasts the duration of treatment and post-treatment reductions in lymphocyte counts. Post hoc analyses, long-term follow-up of populations with RMS in randomised trials, and real-world evidence suggest that the efficacy of CladT is probably independent of age, although more data in the elderly are still needed. No clear adverse signals for lymphopenia or other adverse safety signals have emerged with increasing age, although immunosenescence in the setting of age-related “inflammaging” may predispose elderly patients to a higher risk of infections. Updating vaccination status is recommended, especially against pneumococci and herpes zoster for older patients, to minimise the risk of these infections. CladT may be a useful alternative treatment for ageing people with MS who often bear a burden of multiple comorbidities and polypharmacy and who are more exposed to the adverse effects of continuous immunosuppressive therapy.

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Mortality and cause of death in multiple sclerosis in western Norway 1950–2021: a registry-based linkage study

Cited by 10 publications

References 32 publications

Multiple sclerosis mortality in New Zealand: a nationwide prospective study

Multiple sclerosis mortality in New Zealand: a nationwide prospective study

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

Narrative Review on the Use of Cladribine Tablets as Exit Therapy for Stable Elderly Patients with Multiple Sclerosis

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