Associations of DMT Therapies with COVID-19 Severity in Multiple Sclerosis: An International Cohort Study

Simpson‐Yap, Steve; Ed, Brouwer; Kalinčík, Tomáš; Rijke, Nick; Hillert, J.; Walton, Clare; Edan, Gilles; Moreau, Yvan; Spelman, Tim; Geys, Lotte; Parciak, Tina; Gautrais, Clément; Lazovski, Nikola; Pirmani, Ashkan; Ardeshirdavani, Amin; Forsberg, Lars A.; Glaser, Anna; McBurney, Robert N.; Schmidt, H.; Bergmann, Arnfin; Braune, Stefan; Stahmann, Alexander; Middleton, Rod; Salter, Amber; Fox, R. H.; Avd, Welt; Butzkueven, Helmut; Ji, Rojas; Ivd, Mei; N, Nag; Ivanov, R; GSd, Olival; Ae, Dias; Magyari, Melinda; Dg, Brum; Mf, Mendes; Alonso, Ricardo; Nicholas, Rebecca; Bauer, Jürgen; Chertcoff, Aníbal; Zabalza, Amaya; Arrambide, Georgina; Fidao, Alexander; Comi, G.; Lm, Peeters

doi:10.2139/ssrn.3711429

Cited by 4 publications

(5 citation statements)

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“…Older age and higher disability levels have also been identified as risk factors for a more severe course of COVID-19 in MS (Louapre et al, 2020;Salter et al, 2021;Sormani et al, 2021), In addition, obesity and cardiovascular comorbidity were associated with an increased risk of severe COVID-19 (Louapre et al, 2020;Möhn et al, 2020;Salter et al, 2021). Finally, anti-CD20 antibody treatment was found to be associated with increased risk of severe COVID-19 in several studies (Salter et al, 2021;Simpson-Yap et al, 2021;Sormani et al, 2021). The number of patients hospitalized with COVID-19 in our study was too low to allow for an analysis of risk factors for severe COVID-19.…”

Section: Discussionmentioning

confidence: 56%

“…However, data for anti-CD20 antibody-treated patients with demyelinating diseases are limited and more data would be highly relevant, especially since the overall risk of infection is increasingly recognized as a crucial issue after the emergence of pandemic corona virus disease 2019 (COVID-19) (Zubair et al, 2020). Indeed, some studies indicate that the risk of a more severe COVID-19 disease course is increased in patients treated with anti-CD20 antibodies (Salter et al, 2021;Simpson-Yap et al, 2021;Sormani et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

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Anti-CD20 antibody therapy and risk of infection in patients with demyelinating diseases

Oksbjerg

Nielsen

Blinkenberg

et al. 2021

Multiple Sclerosis and Related Disorders

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Background: Anti-CD20 antibody therapy may be associated with an increased risk of infections. We therefore investigated risk factors for infection in patients with demyelinating diseases treated with anti-CD20 antibody therapy. Methods: In this retrospective uncontrolled study, patients ever treated with anti-CD20 antibodies at an academic clinic were identified through the Danish Multiple Sclerosis Registry (DMSR). Data were collected from medical charts and the DMSR. We assessed occurrence of severe infections (requiring hospitalization), varicella zoster virus (VZV), major comorbidities and routine laboratory values for lymphocytes, IgG and IgM. Results: A total of 447 patients ever treated with anti-CD20 antibody therapy were identified; of these 416 with 649 patient years of follow-up were still under therapy. In this group, seven patients had VZV infections, and 16 patients had been hospitalized with infections during up to three years of follow-up on anti-CD20 therapy. Comorbidity was recorded in 80 patients. The risk of severe infection was associated with comorbidities, higher age, longer duration of treatment, and higher Expanded Disability Status Scale (EDSS) scores. In multivariable analyses treatment duration, EDSS scores and presence of comorbidity were independently associated with risk of severe infections. Serum concentrations of IgG and IgM decreased with increasing duration of therapy but were not associated with risk of severe infections. Patients with VZV infection had lower lymphocyte counts and lower serum concentrations of IgM. In multivariable analyses only lymphocyte counts were independently associated with risk of VZV infection. Conclusions: In this retrospective study of patients treated with anti-CD20 antibodies, the risk of infections requiring hospitalization was independently associated with comorbidities, duration of treatment, and higher EDSS scores. Risk of VZV infection was independently associated with lymphopenia. Future studies investigating strategies for mitigating risk of infection in patients treated with anti-CD20 antibodies are warranted, especially for older patients, patients with higher levels of disability and for patients with a longer duration of treatment.

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Section: Discussionmentioning

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Anti-CD20 antibody therapy and risk of infection in patients with demyelinating diseases

Oksbjerg

Nielsen

Blinkenberg

et al. 2021

Multiple Sclerosis and Related Disorders

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“…COVID-19-related MS mortality has been reported to be approximately 1–4% overall (compared with a case–fatality ratio in the general population of 0.0–9.2% in the 20 countries most affected by COVID-19, including the USA, which has a rate of 1.8% [according to Johns Hopkins University]), and more than 50% of deaths have occurred in people not receiving MS DMTs [ 27 – 29 ]. An analysis of data in people with MS from 28 countries who had suspected or confirmed COVID-19 found that treatment with ocrelizumab or rituximab was associated with significantly increased risk of hospitalization and admission to the intensive care unit compared with other pooled DMTs (including alemtuzumab, cladribine, dimethyl fumarate, fingolimod, glatiramer acetate, interferon, natalizumab, and teriflunomide) [ 30 ]. Rituximab was also associated with significantly increased risk of artificial ventilation [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

“…An analysis of data in people with MS from 28 countries who had suspected or confirmed COVID-19 found that treatment with ocrelizumab or rituximab was associated with significantly increased risk of hospitalization and admission to the intensive care unit compared with other pooled DMTs (including alemtuzumab, cladribine, dimethyl fumarate, fingolimod, glatiramer acetate, interferon, natalizumab, and teriflunomide) [ 30 ]. Rituximab was also associated with significantly increased risk of artificial ventilation [ 30 ]. In a recent retrospective study from electronic health records, interferons and glatiramer acetate were shown to be associated with reduced COVID-19 risk, whereas anti-CD20 therapies were associated with increased risk, within the treated MS cohort [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Vaccine Considerations for Multiple Sclerosis in the COVID-19 Era

et al. 2021

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People with multiple sclerosis (MS) are at risk for infections that can result in amplification of baseline symptoms and possibly trigger clinical relapses. Vaccination can prevent infection through the activation of humoral and cellular immune responses. This is particularly pertinent in the era of emerging novel vaccines against severe acute respiratory syndrome coronavirus 2, the virus that causes coronavirus disease 2019 (COVID-19). MS disease-modifying therapies (DMTs), which affect the immune system, may impact immune responses to COVID-19 vaccines in people with MS. The objective of this article is to provide information on immune system responses to vaccinations and review previous studies of vaccine responses in people with MS to support the safety and importance of receiving currently available and emerging COVID-19 vaccines. Immunological studies have shown that coordinated interactions between T and B lymphocytes of the adaptive immune system are key to successful generation of immunological memory and production of neutralizing antibodies following recognition of vaccine antigens by innate immune cells. CD4 + T cells are essential to facilitate CD8 + T cell and B cell activation, while B cells drive and sustain T cell memory. Data suggest that some classes of DMT, including type 1 interferons and glatiramer acetate, may not significantly impair the response to vaccination. DMTs—such as sphingosine-1-phosphate receptor modulators, which sequester lymphocytes from circulation; alemtuzumab; and anti-CD20 therapies, which rely on depleting populations of immune cells—have been shown to attenuate responses to conventional vaccines. Currently, three COVID-19 vaccines have been granted emergency use authorization in the USA on the basis of promising interim findings of ongoing trials. Because analyses of these vaccines in people with MS are not available, decisions regarding COVID-19 vaccination and DMT choice should be informed by data and expert consensus, and personalized with considerations for disease burden, risk of infection, and other factors.

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“…It could be due to the small sample size in this study, the younger participants, or the lower EDSS. Recent large studies have shown that patients with MS treated with anti-CD20 DMTs (rituximab or ocrelizumab) were at higher risk of developing severe COVID-19 than other DMTs [ 32 , 33 ]; however, strict adherence to health protocols and self-isolation might be an important reason for the low prevalence and severity of COVID-19 infection among our patients.…”

Section: Discussionmentioning

confidence: 85%

Multiple sclerosis and COVID-19: A retrospective study in Iran

et al. 2023

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Objectives Previous studies suggested a higher rate of COVID-19 infection in patients with multiple sclerosis than in the general population, and limited studies addressed the impact of COVID-19 and its vaccination in patients with multiple sclerosis in Iran. We decided to investigate the factors associated with COVID-19 infection, the effects and side effects of the COVID-19 vaccination in patients with multiple sclerosis (MS). Methods We used the data of the patients with multiple sclerosis registered in a referral clinic in Kerman, one of the large cities in Iran (a population of 537,000 inhabitants), to explore the association between demographic variables, the history of COVID-19 vaccination, and the clinical outcomes. Results Of the 367 participants in this study, 88.3% received the COVID-19 vaccine, 35.4% were confirmed COVID-19 cases, and the incidence of COVID-19 was much higher before vaccination (24.5% before vaccination versus 10.1% after vaccination). The multivariable logistic regression model showed that male gender (OR = 2.64, 95% confidence interval: 1.21, 5.74) and current employment (OR = 3.04, 95% confidence interval: 1.59, 5.80) were associated with an increased risk of COVID-19. The only factor associated with the adverse effects of COVID-19 vaccination was the type of vaccine (AstraZeneca). Conclusion Our findings showed that the vaccination protected MS cases considerably against COVID-19. In addition, the side effects of the vaccines were not noticeably high in these cases as well. Among all COVID-19 vaccines, AstraZeneca had the most common side effects, so people must be aware of them before vaccination. The male gender and employment were the most important variables in the prevalence of COVID-19 in patients with multiple sclerosis in our study.

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Associations of DMT Therapies with COVID-19 Severity in Multiple Sclerosis: An International Cohort Study

Cited by 4 publications

References 0 publications

Anti-CD20 antibody therapy and risk of infection in patients with demyelinating diseases

Anti-CD20 antibody therapy and risk of infection in patients with demyelinating diseases

Vaccine Considerations for Multiple Sclerosis in the COVID-19 Era

Multiple sclerosis and COVID-19: A retrospective study in Iran

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