scholarly journals 1298Associations of DMT therapies with COVID-19 severity in multiple sclerosis

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Steve Simpson-Yap ◽  
Edward De Brouwer ◽  
Tomas Kalincik ◽  
Nick Rijke ◽  
Jan Hillert ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Artificial Ventilation ◽  
Dimethyl Fumarate ◽  
Mixed Effects ◽  
Vulnerable Group ◽  
Cross Sectional ◽  
Disease Modifying Therapies ◽  
External Consistency ◽  
Cross Sectional Design ◽  
Anti Cd20

Abstract Background People with multiple sclerosis (MS) are a vulnerable group for severe COVID-19, particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS. Methods Data from 12 data-sources in 28 countries were aggregated (sources could include patients from 1-12 countries). Demographic (age, sex), clinical (MS phenotype, disability), and DMT (untreated, alemtuzumab, cladribine, dimethyl-fumarate, glatiramer-acetate, interferon, natalizumab, ocrelizumab, rituximab, siponimod, other) covariates were queried, alongside COVID-19 hospitalisation, admission to ICU, requiring artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression, adjusted for age, sex, MS phenotype, and EDSS. Results 657 (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19 were analysed. Among suspected+confirmed/confirmed-only COVID-19, 20.9%/26.9% were hospitalised, 5.4%/7.2% were admitted to ICU, 4.1%/5.4% required artificial ventilation, and 3.2%/3.9% died. Older age, progressive MS-phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl-fumarate, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.56,95%CI=1.01-2.41; aOR=2.43,95%CI=1.48-4.02) and ICU admission (aOR=2.30,95%CI=0.98-5.39; aOR=3.93,95%CI=1.56-9.89), though only rituximab was associated with higher risk of artificial ventilation (aOR=4.00,95%CI=1.54-10.39). Importantly, associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Conclusions Despite the cross-sectional design of this study, the internal and external consistency of these results with prior studies suggests their use may be a risk factor for more severe COVID-19. Key messages Anti-CD20 DMTs may be associated with worse COVID-19 severity amongst people with multiple sclerosis.

scholarly journals Associations of Disease-Modifying Therapies With COVID-19 Severity in Multiple Sclerosis

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012753
Author(s):  
Steve Simpson-Yap ◽  
Edward De Brouwer ◽  
Tomas Kalincik ◽  
Nick Rijke ◽  
Jan A Hillert ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Artificial Ventilation ◽  
Dimethyl Fumarate ◽  
Cross Sectional ◽  
Icu Admission ◽  
Disease Modifying Therapies ◽  
Increased Risk ◽  
External Consistency ◽  
Disease Modifying ◽  
Cross Sectional Design

Background:People with multiple sclerosis (MS) are a vulnerable group for severe COVID- 19, particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS.Methods:Data from 12 data-sources in 28 countries were aggregated (sources could include patients from 1-12 countries). Demographic (age, sex), clinical (MS-phenotype, disability), and DMT (untreated, alemtuzumab, cladribine, dimethyl-fumarate, glatiramer acetate, interferon, natalizumab, ocrelizumab, rituximab, siponimod, other DMTs) covariates were queried, alongside COVID-19 severity outcomes, hospitalisation, ICU admission, requiring artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression, adjusted for age, sex, MS-phenotype, and EDSS.Results:657(28.1%) with suspected and 1,683(61.9%) with confirmed COVID-19 were analysed. Among suspected+confirmed and confirmed-only COVID-19, 20.9% and 26.9% were hospitalised, 5.4% and 7.2% were admitted to ICU, 4.1% and 5.4% required artificial ventilation, and 3.2% and 3.9% died. Older age, progressive MS-phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl-fumarate, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.56,95%CI=1.01- 2.41; aOR=2.43,95%CI=1.48-4.02) and ICU admission (aOR=2.30,95%CI=0.98-5.39;aOR=3.93,95%CI=1.56-9.89), though only rituximab was associated with higher risk of artificial ventilation (aOR=4.00,95%CI=1.54-10.39). Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.75,95%CI=1.29- 2.38; aOR=2.76,95%CI=1.87-4.07) and ICU admission (aOR=2.55,95%CI=1.49-4.36;aOR=4.32,95%CI=2.27-8.23) but only rituximab with artificial ventilation (aOR=6.15,95%CI=3.09-12.27). Compared to natalizumab, ocrelizumab and rituximab wereassociated with hospitalisation (aOR=1.86,95%CI=1.13-3.07; aOR=2.88,95%CI=1.68-4.92) and ICU admission (aOR=2.13,95%CI=0.85-5.35; aOR=3.23,95%CI=1.17-8.91), but only rituximab with ventilation (aOR=5.52,95%CI=1.71-17.84). Importantly, associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Stratification by age, MS-phenotype, and EDSS found no indications that DMT associations with COVID-19 severity reflected differential DMT allocation by underlying COVID-19 severity.Conclusions:Using the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalisation, ICU admission, and requiring artificial ventilation, and ocrelizumab with hospitalisation and ICU admission. Despite the study’s cross-sectional design, the internal and external consistency of these results with prior studies suggests rituximab/ocrelizumab use may be a risk factor for more severe COVID-19.

scholarly journals Associations of DMT therapies with COVID-19 severity in multiple sclerosis

2021 ◽  
Author(s):  
Steve Simpson-Yap ◽  
Edward De Brouwer ◽  
Tomas Kalincik ◽  
Nick Rijke ◽  
Jan Hillert ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Artificial Ventilation ◽  
Dimethyl Fumarate ◽  
Mixed Effects ◽  
Clinical Severity ◽  
Vulnerable Group ◽  
Icu Admission ◽  
Disease Modifying Therapies ◽  
Increased Risk ◽  
Clinical Covariates

AbstractBackgroundPeople with multiple sclerosis (MS) are a vulnerable group for severe COVID-19, particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS.MethodsData from 12 data-sources in 28 countries were aggregated. Demographic and clinical covariates were queried, alongside COVID-19 clinical severity outcomes, hospitalisation, admission to ICU, requiring artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression.Results657 (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19 were analysed. Older age, progressive MS-phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl fumarate, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.56,95%CI=1.01-2.41; aOR=2.43,95%CI=1.48-4.02) and ICU admission (aOR=2.30,95%CI=0.98-5.39; aOR=3.93,95%CI=1.56-9.89), though only rituximab was associated with higher risk of artificial ventilation (aOR=4.00,95%CI=1.54-10.39). Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.75,95%CI=1.29-2.38; aOR=2.76,95%CI=1.87-4.07) and ICU admission (aOR=2.55,95%CI=1.49-4.36; aOR=4.32,95%CI=2.27-8.23) but only rituximab with artificial ventilation (aOR=6.15,95%CI=3.09-12.27). Compared to natalizumab, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.86,95%CI=1.13-3.07; aOR=2.88,95%CI=1.68-4.92) and ICU admission (aOR=2.13,95%CI=0.85-5.35; aOR=3.23,95%CI=1.17-8.91), but only rituximab with ventilation (aOR=5.52,95%CI=1.71-17.84). Importantly, associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death.ConclusionsUsing the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalisation, ICU admission, and requiring artificial ventilation, and ocrelizumab with hospitalisation and ICU admission, suggesting their use may be a risk factor for more severe COVID-19.

scholarly journals Impact of COVID-19 on multiple sclerosis care and management: Results from the European Committee for Treatment and Research in Multiple Sclerosis survey

2021 ◽  
pp. 135245852110053
Author(s):  
Emilio Portaccio ◽  
Mattia Fonderico ◽  
Bernhard Hemmer ◽  
Tobias Derfuss ◽  
Bruno Stankoff ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Access To Care ◽  
Online Survey ◽  
Dimethyl Fumarate ◽  
Standards Of Care ◽  
Treatment Practices ◽  
European Committee ◽  
Disease Modifying Therapy ◽  
Anti Cd20 ◽  
The Impact

Background: The spread of Coronavirus disease-19 (COVID-19) poses unique challenges in the management of people with multiple sclerosis (PwMS). Objectives: To collect data about the impact of COVID-19 emergency on access to care for PwMS and on MS treatment practices. Methods: Between March and July 2020, the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) promoted an online survey covering patient access to care, management of relapses and visits, disease-modifying therapy (DMT) and experience with COVID-19. Results: Three-hundred and sixty neurologists from 52 countries (68% from Europe) completed the survey. 98% reported COVID-19-related restrictions. Telemedicine was adopted to overcome the limited access to care and was newly activated (73%) or widely implemented (17%). 70% reported changes in DMT management. Interferons and glatiramer were considered safe. Dimethyl fumarate, teriflunomide and fingolimod were considered safe except for patients developing lymphopenia. No modifications were considered for natalizumab in 64%, cladribine in 24%, anti-CD20 in 22% and alemtuzumab in 17%; 18% (for alemtuzumab and cladribine) and 43% (for anti-CD20) considered postponing treatment. Conclusion: The ECTRIMS survey highlighted the challenges in keeping standards of care in clinical practice. Telemedicine clearly needs to be implemented. Gathering data on DMT safety will remain crucial to inform treatment decisions.

scholarly journals JC Virus Seroprevalence and JCVAb Index in Polish Multiple Sclerosis Patients Treated with Immunomodulating or Immunosuppressive Therapies

2021 ◽  
Vol 10 (9) ◽  
pp. 1998
Author(s):  
Robert Bonek ◽  
Wojciech Guenter ◽  
Robert Jałowiński ◽  
Anna Karbicka ◽  
Anna Litwin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Jc Virus ◽  
Dimethyl Fumarate ◽  
Risk Category ◽  
Seroprevalence Rate ◽  
Immunomodulatory Drugs ◽  
Cross Sectional ◽  
Treatment Type ◽  
Multiple Sclerosis Patients ◽  
The Impact

The use of a highly-effective treatment for multiple sclerosis (MS) is associated with a severe risk of developing complications, such as progressive multifocal leukoencephalopathy (PML) caused by the John Cunningham virus (JCV). The aim of this study was to evaluate the correlation between anti-JCV Ab seroprevalence, anti-JCV AI, demographic and clinical factors as well as the type of therapy used in the Polish MS population. This is a multicentre, prospective and cross-sectional study involving 1405 MS patients. The seroprevalence of anti-JCV Ab and anti-JCV AI levels as well as AI categories were analysed with the use of a second-generation two-step ELISA test (STRATIFY JCV DxSelect). The overall prevalence of anti-JCV Ab was 65.8%. It was shown that seroprevalence increases with the patient’s age. The seroprevalence was significantly associated with the treatment type, and the highest values (76%) were obtained from immunosuppressant-treated patients. Overall, 63.3% of seropositive patients had an antibody index (AI) level of >1.5. In the seropositive patient group, the mean AI level amounted to 2.09. Similarly to the seroprevalence, AI levels correlated with the patient’s age; AI level for patients above 40 years old and from subsequent age quintiles plateaued, amounting to at least 1.55. Patients treated with immunosuppressants and immunomodulatory drugs obtained the highest (1.67) and lowest (1.35) AI levels, respectively. Of the immunosuppressants used, the highest mean AI levels were observed in mitoxantrone and cladribine groups, amounting to 1.75 and 1.69, respectively. In patients treated with immunomodulatory drugs, the lowest AI levels were observed in the dimethyl fumarate (DMF) group (1.11). The seroprevalence rate in the Polish MS population is one of the highest in Europe. The majority of seropositive patients had an anti-JCV Ab level qualifying them for a high-risk category. The highest mean AI levels are observed in patients receiving immunosuppressants, especially mitoxantrone and cladribine. Patients receiving immunomodulatory drugs have lower AI levels compared to treatment-naïve subjects, especially when treated with DMF. Further studies, especially longitudinal studies, are required to determine the impact of MS drugs on the seroprevalence of anti-JCV Ab and AI levels.

scholarly journals Use of newer disease-modifying therapies in pediatric multiple sclerosis in the US

Neurology ◽  
2018 ◽  
Vol 91 (19) ◽  
pp. e1778-e1787 ◽  
Author(s):  
Kristen M. Krysko ◽  
Jennifer Graves ◽  
Mary Rensel ◽  
Bianca Weinstock-Guttman ◽  
Gregory Aaen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Side Effect ◽  
Pediatric Patients ◽  
Dimethyl Fumarate ◽  
Short Term ◽  
Pediatric Multiple Sclerosis ◽  
Disease Modifying Therapies ◽  
The Us ◽  
Disease Modifying

ObjectiveTo characterize the use and safety of newer disease-modifying therapies (DMTs) in children with multiple sclerosis (MS) and clinically isolated syndrome (CIS) treated under 18 years of age.MethodsThis is a cohort study including children with MS or CIS followed at 12 outpatient practices participating in the US Network of Pediatric MS Centers. DMT use, including duration, dose, and side effects, was analyzed. Newer DMTs were defined as agents receiving Food and Drug Administration approval or with increased use in adult MS after 2005.ResultsAs of July 2017, 1,019 pediatric patients with MS (n = 748) or CIS (n = 271) were enrolled (65% female, mean onset 13.0 ± 3.9 years, mean follow-up 3.5 ± 3.1 years, median 1.6 visits per year). Of these, 78% (n = 587) with MS and 11% (n = 31) with CIS received DMT before 18 years of age. This consisted of at least one newer DMT in 42%, including dimethyl fumarate (n = 102), natalizumab (n = 101), rituximab (n = 57), fingolimod (n = 37), daclizumab (n = 5), and teriflunomide (n = 3). Among 17%, the initial DMT prescribed was a newer agent (36 dimethyl fumarate, 30 natalizumab, 22 rituximab, 14 fingolimod, 2 teriflunomide). Over the last 10 years, the use of newer agents has increased, particularly in those ≥12 years and to lesser extent in those <12 years. The short-term side effect profiles of newer DMTs did not differ from those reported in adults.ConclusionNewer DMTs are often used in pediatric MS, and have similar short-term safety, tolerability, and side effect profiles as in adults. These findings may help inform pediatric MS management.

scholarly journals Predictors of adherence and persistence to disease-modifying therapies in Multiple Sclerosis

2021 ◽  
Vol 14 ◽  
pp. 175628642110310
Author(s):  
Gisela Zanga ◽  
Estefania Drzewiscki ◽  
Paula Tagliani ◽  
Maximiliano Smietniansky ◽  
Maria M. Esnaola y Rojas ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Medication Possession Ratio ◽  
Care Program ◽  
Cross Sectional Study ◽  
Response To Treatment ◽  
Cross Sectional ◽  
National Medical ◽  
Disease Modifying Therapies ◽  
Disease Modifying ◽  
Predictors Of Adherence

Background and Aims: In multiple sclerosis (MS), non-adherence/non-persistence is related to suboptimal response to treatment, including disease relapses and the need for more expensive healthcare. The aim of this study was to identify predictors related to adherence to disease modifying therapies (DMTs) in a cohort of Argentinian MS patients. Methods: We conducted a cross-sectional study at the National Medical Care Program from Argentina. MS patients with at least one claim for a DMT from 1 January 2017 to 1 October 2017 were identified. A telephone survey was performed to assess clinical and demographic factors. The medication possession ratio (MPR) was used to estimate adherence; MPR <80% defined non-adherence. Associations were studied using a logistic regression model. Results: Our database included 648 MS patients. A total of 360 patients (60% females, mean age 55.3 years) accepted to participate. Of these, 308 (85.5%) patients were receiving DMT at the time of the survey. Some 198 (63.7%) were receiving injectable therapies. Optimal adherence was 47.7%. Adherence was associated with oral medication [odds ratio (OR) 1.83 95% confidence interval (CI) 1.13–3.00, p = 0.014]. A factor related to oral drugs was higher educational level (OR 2.86 95%CI 1.41–5.81, p = 0.004). Conclusion: This real-world study showed better adherence and persistence on treatment with oral therapies in MS patients in Argentina.

Effect of lateral therapy switches to oral moderate-efficacy drugs in multiple sclerosis: a nationwide cohort study

2021 ◽  
pp. jnnp-2020-324869 ◽  
Author(s):  
Mathias Due Buron ◽  
Tomas Kalincik ◽  
Finn Sellebjerg ◽  
Per Soelberg Sørensen ◽  
Melinda Magyari
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Absolute Risk ◽  
Dimethyl Fumarate ◽  
Interferon Β ◽  
First Line ◽  
Disease Modifying Therapies ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

BackgroundSwitching between first-line disease-modifying therapies in patients with clinically stable relapsing–remitting multiple sclerosis (RRMS) due to reasons other than disease activity is frequent, but evidence on the effect of this practice is limited. We investigated the effect of switching patients with stable RRMS on occurrences of disability accumulation, relapses and future treatment discontinuation.MethodsUsing the Danish Multiple Sclerosis Registry, we identified patients with RRMS without disease activity who either (1) stayed on injectable platform therapy (interferon-β or glatiramer acetate) or (2) switched to dimethyl fumarate (DMF) or teriflunomide (TFL) and compared treatment outcomes using propensity-score-based methods and marginal structural models (MSM).ResultsWe included 3206 patients in the study. We found no change in risk of 6-month confirmed Expanded Disability Status Scale score worsening in patients switching to DMF (HR: 1.15, 95% CI 0.88 to 1.50) or TFL (HR: 1.16, 95% CI 0.92 to 1.46). The risk of suffering any relapse tended to decrease when switching to DMF (HR: 0.73, 95% CI 0.51 to 1.04) and tended to increase when switching to TFL (HR: 1.25, 95% CI 0.96 to 1.63). Absolute risk differences were small. MSM analyses showed similar results but did not find an increased relapse risk in TFL switchers.ConclusionSwitching from injectable platform therapies to oral first-line therapies in patients with clinically stable RRMS does not increase the risk of disability accumulation. While the postswitch risk of relapses trended towards marginally higher on TFL, this trend was eliminated by adjustment for time-variant confounders.

scholarly journals Assessing Pharmacists’ Preferences towards Efficacy Attributes of Disease-Modifying Therapies in Relapsing-Remitting Multiple Sclerosis

Pharmacy ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 61
Author(s):  
Iciar Martínez-López ◽  
Jorge Maurino ◽  
Patricia Sanmartín-Fenollera ◽  
Ana Ontañon-Nasarre ◽  
Alejandro Santiago-Pérez ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Critical Role ◽  
Cross Sectional ◽  
Hospital Pharmacists ◽  
Disease Modifying Therapies ◽  
Hypothetical Treatment ◽  
Related Quality ◽  
Health Related ◽  
Disease Modifying

Introduction: Hospital pharmacists are increasingly playing a critical role in the care of patients with multiple sclerosis (MS). However, little is known about their preferences and perspectives towards different attributes of disease-modifying therapies (DMTs). The objective of this research was to assess pharmacists´ preferences for DMT efficacy attributes. Methods: A multicenter, non-interventional, cross-sectional, web-based study was conducted. Preventing relapses, delaying disease progression, controlling radiological activity, and preserving health-related quality of life (HRQoL) and cognition were the attributes selected based on a literature review and a focus group with six hospital pharmacists. Conjoint analysis was used to determine preferences in eight hypothetical treatment scenarios, combining different levels of each attribute and ranking them from most to least preferred. Results: Sixty-five hospital pharmacists completed the study (mean age: 43.5 ± 7.8 years, 63.1% female, mean years of professional experience: 16.1 ± 7.4 years). Participants placed the greatest preference on delaying disease progression (35.7%) and preserving HRQoL (21.6%) and cognition (21.6%). Importance was consistent in all groups of pharmacists stratified according to demographic characteristics, experience, research background, and volume of patients seen per year. Conclusions: Understanding which treatment characteristics are meaningful to hospital pharmacists may help to enhance their synergistic role in the multidisciplinary management of patients with MS.

The association between cognitive impairment and physical disability in multiple sclerosis

2005 ◽  
Vol 11 (4) ◽  
pp. 469-476 ◽  
Author(s):  
Sharon G Lynch ◽  
Brett A Parmenter ◽  
Douglas R Denney
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
Physical Disability ◽  
Cross Sectional ◽  
Delayed Recall ◽  
Physical Decline ◽  
Disability Status ◽  
Duration Of Disease ◽  
Cross Sectional Design ◽  
The Relationship

Background: The association between cognitive impairment and physical disability was examined in a larger, more representative sample of patients with multiple sclerosis (MS) than in previous studies. Method: Two hundred and fifty-three patients attending an MS clinic were assessed with respect to physical disability using the Expanded Disability Status Scale and cognitive impairment using a battery of neuropsychological tests. Results: Physical disability correlated with duration of disease; cognitive impairment did not. Virtually all measures derived from the cognitive battery were significantly correlated with physical disability. Three measures of speeded information processing and one involving delayed recall of verbal material were unique predictors of disability status. The relationship between cognitive impairment and physical disability was equivalent for patients with shorter (<3 years) versus longer (>10 years) disease duration. Cognitive impairment correlated with the rate of disability progression as reflected by the progression index. Conclusion: Cognitive impairment is more closely associated with physical disability than most previous studies indicate. This relationship appears to be stable throughout the duration of MS, although this conclusion is qualified by the cross-sectional design of the study. Further attention should be paid to cognitive impairment as a possible predictor of the rate of patients’ physical decline.

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