Comorbid conditions commonly affect people with multiple sclerosis (MS). Population-based studies indicate that people with MS have an increased incidence of ischemic heart disease, cerebrovascular disease, peripheral vascular disease, and psychiatric disorders as compared to people without MS. People with MS from underrepresented minority and immigrant groups have higher comorbidity burdens. Comorbidities exert effects throughout the disease course, from symptom onset through diagnosis to the end of life. At the individual level, comorbidity is associated with higher relapse rates, greater physical and cognitive impairments, lower health-related quality of life, and increased mortality. At the level of the health system and society, comorbidity is associated with increased health care utilization, costs and work impairment. A nascent literature suggests that MS affects outcomes from comorbidities. Comorbidity management needs to be integrated into MS care, and this would be facilitated by determining optimal models of care.

https://www.frontiersin.org/articles/10.3389/fimmu.2023.1197195/pdf

Etiology, effects and management of comorbidities in multiple sclerosis: recent advances

Neuroimmunological diseases and their treatment compromise the immune system, thereby increasing the risk of infections and serious illness. Consequently, vaccinations to protect against infections are an important part of the clinical management of these diseases. However, the wide variety of immunotherapies that are currently used to treat neuroimmunological disease - particularly multiple sclerosis and neuromyelitis optica spectrum disorders - can also impair immunological responses to vaccinations. In this Review, we discuss what is known about the effects of various immunotherapies on immunological responses to vaccines and what these effects mean for the safe and effective use of vaccines in patients with a neuroimmunological disease. The success of vaccination in patients receiving immunotherapy largely depends on the specific mode of action of the immunotherapy. To minimize the risk of infection when using immunotherapy, assessment of immune status and exclusion of underlying chronic infections before initiation of therapy are essential. Selection of the required vaccinations and leaving appropriate time intervals between vaccination and administration of immunotherapy can help to safeguard patients. We also discuss the rapidly evolving knowledge of how immunotherapies affect responses to SARS-CoV-2 vaccines and how these effects should influence the management of patients on these therapies during the COVID-19 pandemic. 

/pdf/vaccination-and-immunotherapies-in-neuroimmunological-268iy3gl.pdf

Vaccination and immunotherapies in neuroimmunological diseases

Fatigue and depression are common conditions diagnosed in people with multiple sclerosis (MS). Fatigue defined as subjective lack of physical and/or mental energy is present in 35–97% of people with MS, who classify it as one of the most serious symptoms interfering with daily activities and influencing the quality of life. Depression is diagnosed in about 50% of people with MS. Since fatigue and depression frequently coexists, it may be quite hard to differentiate them. Primary fatigue and primary depression in MS are caused by inflammatory, oxidative/nitrosative, and neurodegenerative processes leading to demyelination, axonal damage, and brain atrophy. In people with MS and comorbid fatigue and/or depression there is reported increased serum and cerebrospinal fluid concentration of inflammatory mediators such as tumor necrosis factor, interleukins (IL-1a, IL-1b, IL-6), interferon γ and neopterin. Moreover, the brain atrophy of prefrontal, frontal, parietotemporal regions, thalamus, and basal ganglia was observed in people with MS with fatigue and/or depression. The secondary fatigue and secondary depression in people with MS may be caused by emotional factors, sleep disorders, pain, the coexistence of other diseases, and the use of medications. In some studies, the use of disease-modifying therapies positively influenced fatigue, probably by reducing the inflammatory response, which proves that fatigue and depression are closely related to immunological factors. In this mini-review, the pathogenesis, methods of evaluation and differentiation, and possible therapies for fatigue and depression in MS are discussed.

Co-occurrence of Fatigue and Depression in People With Multiple Sclerosis: A Mini-Review

Abstract Objectives To investigate the incidence of COVID-19 hospitalisation in unvaccinated and vaccinated patients with rheumatoid arthritis (RA) compared with matched controls, and in patients with RA according to DMARD treatment. Methods Danish nationwide matched cohort study from January to October 2021. Patients with RA were identified in the DANBIO register and matched 1:20 with individuals from the general population on age, sex, and vaccination status. Primary and secondary outcomes were COVID-19 hospitalisation (Danish National Patient Register) and first-time positive SARS-CoV2 PCR test (Danish COVID-19 Surveillance Register), respectively. Stratified by vaccination status, incidence rates (IRs) per 1000 person years (PY) and comorbidity-adjusted hazard ratios (aHRs) in cause-specific Cox models were calculated with 95% confidence intervals. Results In total, 28 447 unvaccinated patients and 568 940 comparators had Irs for COVID-19 hospitalisation of 10.4 (8.0–13.4) and 4.7 (4.3–5.1) per 1000 PY, respectively (aHR 1.88, 1.44–2.46). When fully vaccinated, corresponding Irs were 0.9 (0.5–1.6) and 0.5 (0.4–0.6) per 1000 PY (aHR 1.94, 1.03–3.66). Unvaccinated RA patients had an aHR of 1.22 (1.09–1.57) for testing positive for SARS-CoV2 and 1.09 (0.92–1.14) among vaccinated. Vaccinated rituximab-treated patients had increased crude IR of COVID-19 hospitalisation compared with conventional DMARD treated patients. Conclusion The incidence of COVID-19 hospitalisation was increased for both unvaccinated and vaccinated patients with RA compared with controls. Importantly, the parallel decreasing risk for patients with RA suggests a comparable relative benefit of vaccination in most patients.

/pdf/covid-19-infection-and-hospitalisation-risk-according-to-6y4f8e7n.pdf

COVID-19 infection and hospitalisation risk according to vaccination status and DMARD treatment in patients with rheumatoid arthritis

This cohort study assesses the association of anti-CD20 therapies with risk of severe COVID-19 in a French cohort of patients with relapsing-remitting or progressive multiple sclerosis.

/pdf/association-between-anti-cd20-therapies-and-covid-19-1nq51f4c.pdf

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

Background:Depression and use of antidepressants are more common among patients with multiple sclerosis (MS) compared to the general population, but the relation of psychiatric comorbidity to use o...

https://journals.sagepub.com/doi/pdf/10.1177/13524585211031128

Risk of depression in multiple sclerosis across disease-modifying therapies.

BackgroundExercise studies including only fatigued persons with multiple sclerosis (PwMS) with fatigue as primary endpoint are lacking.ObjectiveTo evaluate the effects of high-intensity resistance training (HIRT) on self-reported fatigue in fatigued PwMS in a single center randomised controlled trial.MethodsWe recruited 71 PwMS scoring ≥ 53 on the Fatigue Scale for Motor and Cognitive Functions (FSMC), who were randomised 1:1 to either twice (group A) or once (group B) weekly supervised HIRT for twelve weeks. A non-randomised FSMC score-matched group (n=69) served as non-intervention control.ResultsBetween HIRT-group differences were non-significant for primary and most secondary endpoints. Mean difference in FSMC score (95% confidence intervals) was -10.9 (-14.8; -6.9) in group A and -9.8 (-13.2; -6.3) in group B. Corresponding values for combined HIRT groups vs non-intervention control were -10.3 (-12.9; -7.7) and 1.5 (-0.6;3.6), respectively, p<0.001. Secondary endpoints also improved in both HIRT groups, though only Hospital Anxiety and Depression Scale anxiety and MS Impact Scale-29 psychological subscales significantly favoured the twice a week HIRT (group A). As an exploratory endpoint, changes in plasma inflammatory protein markers were associated with reduced FSMC scores in the pooled material.ConclusionThe finding that HIRT in fatigued PwMS leads to clinically relevant reductions in self-reported fatigue, associated with changes in plasma inflammatory protein levels, provide evidence for recommending HIRT for fatigued PwMS. 

High-intensity resistance training in people with multiple sclerosis experiencing fatigue: A randomised controlled trial.

Rituximab Infusion Timing, Cumulative Dose, and Hospitalization for COVID-19 in Persons With Multiple Sclerosis in Sweden

Background: There is a paucity of information on maternal multiple sclerosis (MS) and risk of adverse pregnancy and perinatal outcomes. Objective: The aim of this study was to determine the association between MS and risks of adverse pregnancy and perinatal outcomes in women with MS. In women with MS, the influence of exposure to disease-modifying therapy (DMT) was also investigated. Methods: Population-based retrospective cohort study on singleton births to mothers with MS and matched MS-free mothers from the general population in Sweden between 2006 and 2020. Women with MS were identified through Swedish health care registries, with MS onset before child’s birth. Results: Of 29,568 births included, 3418 births were to 2310 mothers with MS. Compared with MS-free controls, maternal MS was associated with increased risks of elective caesarean sections, instrumental delivery, maternal infection and antepartum haemorrhage/ placental abruption. Compared with offspring of MS-free women, neonates of mothers with MS were at increased risks of medically indicated preterm birth and being born small for gestational age. DMT exposure was not associated with increased risks of malformations. Conclusions: While maternal MS was associated with a small increased risk of few adverse pregnancy and neonatal outcomes, DMT exposure close to pregnancy was not associated with major adverse outcomes.

Multiple sclerosis, disease-modifying drugs and risk for adverse perinatal and pregnancy outcomes: Results from a population-based cohort study

Background It remains unclear whether and to what extent health behaviours may prolong survival and compress the period of survival with disability. Objective To identify modifiable health behaviours that are associated with later disability onset and longer disability-free survival. Design This population-based cohort study used data from the Swedish National Study on Ageing and Care in Kungsholmen (SNAC-K) ranging between 2001 and 2016. Setting and subjects A total of 3,041 disability-free adults aged ≥60 years were followed up to 15 years. Methods Data on health behaviours were collected at baseline. Information on limitations in activities of daily living was obtained at baseline and during the follow-up. Laplace regression was used to model the median age at death and disability occurrence as a function of health behaviours. Results Never smoking, moderate alcohol drinking, rich social network and high leisure activity were individually related to longer survival by 1-3 years. Participants with high leisure activity lived 1.6 years (95% CI: 0.9-2.3) more without a disability. After combining lifestyle factors, social network, and leisure activities into a 4-level 'health behaviour profile', people with the healthiest behaviour profile lived 2.8 years (95% CI: 1.3-4.2) longer, had disability 3.5 years (95% CI: 1.7-5.3) later and lived 0.7 years (95% CI, 0.4-1.1) more without a disability compared to those with the least healthy behaviours profile. Conclusions These findings suggest that health behaviours could prolong the lifespan, and leisure activities may further compress years lived with disability among older adults.

Can health behaviours prolong survival and compress the period of survival with the disability? A population-based cohort study

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