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 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 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 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.

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.

scholarly journals Use of Disease-Modifying Therapies in Pediatric Relapsing-Remitting Multiple Sclerosis in the United Kingdom

2021 ◽  
Vol 8 (4) ◽  
pp. e1008
Author(s):  
Omar A. Abdel-mannan ◽  
Celeste Manchoon ◽  
Thomas Rossor ◽  
Justine-Clair Southin ◽  
Carmen Tur ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Modifying Therapies ◽  
Increased Risk ◽  
Relapsing Remitting ◽  
Relapse Time ◽  
Disease Modifying ◽  
Edss Score ◽  
Remitting Multiple Sclerosis ◽  
Time To Relapse ◽  
Relapsing Remitting Multiple Sclerosis

ObjectivesTo compare the real-world effectiveness of newer disease-modifying therapies (DMTs) vs injectables in children with relapsing-remitting multiple sclerosis (RRMS).MethodsIn this retrospective, multicenter study, from the UK Childhood Inflammatory Demyelination Network, we identified children with RRMS receiving DMTs from January 2012 to December 2018. Clinical and paraclinical data were retrieved from the medical records. Annualized relapse rates (ARRs) before and on treatment, time to relapse, time to new MRI lesions, and change in Expanded Disability Status Scale (EDSS) score were calculated.ResultsOf 103 children treated with DMTs, followed up for 3.8 years, relapses on treatment were recorded in 53/89 (59.5%) on injectables vs 8/54 (15%) on newer DMTs. The ARR was reduced from 1.9 to 1.1 on injectables (p < 0.001) vs 1.6 to 0.3 on newer DMTs (p = 0.002). New MRI lesions occurred in 77/89 (86.5%) of patients on injectables vs 26/54 (47%) on newer DMTs (p = 0.0001). Children on newer DMTs showed longer time to relapse, time to switch treatment, and time to new radiologic activity than patients on injectables (log-rank p < 0.01). After adjustment for potential confounders, multivariable analysis showed that injectables were associated with 12-fold increased risk of clinical relapse (adjusted hazard ratio [HR] = 12.12, 95% CI = 1.64–89.87, p = 0.015) and a 2-fold increased risk of new radiologic activity (adjusted HR = 2.78, 95% CI = 1.08–7.13, p = 0.034) compared with newer DMTs. At 2 years from treatment initiation, 38/103 (37%) patients had MRI activity in the absence of clinical relapses. The EDSS score did not change during the follow-up, and only 2 patients had cognitive impairment.ConclusionNewer DMTs were associated with a lower risk of clinical and radiologic relapses in patients compared with injectables. Our study adds weight to the argument for an imminent shift in practice toward the use of newer, more efficacious DMTs in the first instance.Classification of EvidenceThis study provides Class IV evidence that newer DMTs (oral or infusions) are superior to injectables (interferon beta/glatiramer acetate) in reducing both clinical relapses and radiologic activity in children with RRMS.

scholarly journals Efficacy and tolerability of oral versus injectable disease-modifying therapies for multiple sclerosis in clinical practice

2016 ◽  
Vol 2 ◽  
pp. 205521731667786 ◽  
Author(s):  
Erin E Longbrake ◽  
Anne H Cross ◽  
Amber Salter
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Practice ◽  
Proportional Hazards ◽  
Dimethyl Fumarate ◽  
Cox Proportional Hazards ◽  
Oral Disease ◽  
Sensitivity Analyses ◽  
Drug Discontinuation ◽  
Disease Modifying Therapies ◽  
Disease Modifying

Background The advent of oral disease-modifying therapies fundamentally changed the treatment of multiple sclerosis. Nevertheless, impressions of their relative efficacy and tolerability are primarily founded on expert opinion. Objective The purpose of this study was to determine whether oral disease-modifying therapies were better tolerated and/or more effective for controlling multiple sclerosis compared to injectable therapies in clinical practice. Methods Single-center, retrospective cohort study. 480 patients initiated oral (fingolimod, teriflunomide, or dimethyl fumarate) or injectable therapy between March 2013–March 2015 and follow-up data was collected for 5–31 months. Outcomes included on-drug multiple sclerosis activity and drug discontinuation. Cox proportional hazards models were used to control for baseline differences and sensitivity analyses using propensity-weighted matching were performed. Results A higher proportion of teriflunomide-treated patients experienced multiple sclerosis activity compared to those treated with injectable therapies ( p = 0.0053) in the adjusted model. Breakthrough multiple sclerosis was equally prevalent among fingolimod and dimethyl fumarate-treated compared to injectable therapy-treated patients. Of patients initiating a disease-modifying therapy, 32–46% discontinued or switched treatments during the study. After controlling for baseline differences, discontinuation rates were comparable across treatment groups. Conclusions In this cohort, oral and injectable disease-modifying therapies were equally well tolerated, but teriflunomide appeared less effective for controlling multiple sclerosis activity than injectable therapies. Further study is needed.

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