Anti-CD20 and COVID-19 in multiple sclerosis and related disorders: A case series of 60 patients from Madrid, Spain

Introduction: Recent studies suggested that anti-CD20 and fingolimod may be associated with lower anti-spike protein-based immunoglobulin-G response following COVID-19 vaccination. We evaluated if COVID-19 occurred despite vaccination among patients with multiple sclerosis (MS) and neuromyelitis optica (NMO), using the COVISEP registry. Case series: We report 18 cases of COVID-19 after two doses of BNT162b2-vaccination, 13 of which treated with anti-CD20 and four with fingolimod. COVID-19 severity was mild. Discussion: These results reinforce the recommendation for a third COVID-19 vaccine dose among anti-CD20 treated patients and stress the need for a prospective clinical and biological study on COVID-19 vaccine efficacy among MS and NMO patients.

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Incidence and Predictive Risk Factors of Infective Events in Patients With Multiple Sclerosis Treated With Agents Targeting CD20 and CD52 Surface Antigens

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz445 ◽

2019 ◽

Vol 6 (11) ◽

Cited By ~ 6

Author(s):

Emanuela Zappulo ◽

Antonio Riccardo Buonomo ◽

Francesco Saccà ◽

Cinzia Valeria Russo ◽

Riccardo Scotto ◽

...

Keyword(s):

Multiple Sclerosis ◽

Bacterial Infections ◽

Viral Infections ◽

Opportunistic Infections ◽

Case Series ◽

Prior Exposure ◽

Cytomegalovirus Reactivation ◽

Immune Impairment ◽

Predictive Risk ◽

Anti Cd20

Abstract Objective Monoclonal antibodies (MAbs) directed against the CD20 and CD52 antigens are used increasingly in patients with multiple sclerosis (MS). Several life-threatening opportunistic infections have been reported in postmarketing case series. The aim of this study was to investigate the incidence of infections and associated prognostic factors during the first year of treatment in patients receiving anti-CD20 (ocrelizumab or rituximab) or anti-CD52 MAbs (alemtuzumab). Methods A retrospective study was conducted in patients with MS referring to the Neurodegenerative Diseases Center at the University of Naples Federico II who received MAbs between November 2015 and June 2018. Results A total of 163 patients were enrolled. Approximately 40% of patients experienced lymphocytopenia during treatment. Eighty-six infective events were reported in 67 patients (41%). Bacterial infections were significantly more frequent with anti-CD20, whereas viral infections prevailed with alemtuzumab. Cytomegalovirus reactivation rates were significantly higher in the alemtuzumab group than in patients on anti-CD20 (51% vs 6%, P < .001). The overall annualized infection rate was 1.1 per patient-year, higher in patients on anti-CD52 versus those on anti-CD20 regimens (1.5 vs 0.8 per patient-year). Alemtuzumab treatment, prior exposure to ≥2 MS drugs, and iatrogenic immune impairment significantly and independently predicted an infection event (adjusted hazard ratio [aHR], 2.7; P = .013; aHR, 1.7; P = .052; and aHR, 2.9; P = .004; respectively). Conclusions Given their considerable infection risk, MS patients receiving MAbs should undergo timely follow up and tailored preventive interventions. Anti-CD52–based treatment, prior exposure to MS drugs, and on-treatment immune impairment are significant predictive factors of infection and their evaluation could help clinicians to stratify a patient’s risk of infection.

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

Multiple Sclerosis Journal ◽

10.1177/13524585211005339 ◽

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.

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COVID-19 in Argentine teriflunomide-treated multiple sclerosis patients: first national case series.

Multiple Sclerosis and Related Disorders ◽

10.1016/j.msard.2021.103049 ◽

2021 ◽

pp. 103049

Author(s):

Geraldine Luetic ◽

María L. Menichini ◽

Marcos Burgos ◽

Ricardo Alonso ◽

Edgar Carnero Contentti ◽

...

Keyword(s):

Multiple Sclerosis ◽

Case Series ◽

Multiple Sclerosis Patients

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Human papillomavirus lesions in 16 MS patients treated with fingolimod: Outcomes and vaccination

Multiple Sclerosis Journal ◽

10.1177/1352458521991433 ◽

2021 ◽

pp. 135245852199143

Author(s):

Elsa Mhanna ◽

Agathe Nouchi ◽

Céline Louapre ◽

Raphael De Paz ◽

Olivier Heinzlef ◽

...

Keyword(s):

Multiple Sclerosis ◽

Human Papillomavirus ◽

Hpv Vaccination ◽

Case Series ◽

Good Tolerance ◽

Prevalence Studies ◽

Disease Modifying Therapies ◽

Disease Modifying ◽

Hpv Screening

Few cases of human papillomavirus (HPV) diseases have been reported in multiple sclerosis (MS) patients treated with fingolimod. We describe a case series of 16 MS patients (11 women, 5 men) developing HPV lesions after the onset of fingolimod, without previous HPV history. Fingolimod had to be discontinued in six patients. Six patients received vaccination for HPV, with good tolerance. Our report highlights that systematic HPV screening and discussion about HPV vaccination before fingolimod onset are crucial. In case of occurrence of HPV lesions during fingolimod treatment, a comprehensive workup of HPV disease is necessary, with discussion of HPV vaccination to prevent secondary lesions. Prevalence studies of HPV lesions are needed in MS patients with the different disease-modifying therapies.

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Safety of alemtuzumab in a nationwide cohort of Finnish multiple sclerosis patients

Journal of Neurology ◽

10.1007/s00415-021-10664-w ◽

2021 ◽

Author(s):

Ilkka Rauma ◽

Tiina Mustonen ◽

Juha Matti Seppä ◽

Maritta Ukkonen ◽

Marianne Männikkö ◽

...

Keyword(s):

Multiple Sclerosis ◽

Adverse Events ◽

Case Series ◽

Retrospective Case ◽

Serious Adverse Events ◽

Highly Active ◽

Disease Modifying Therapy ◽

Case Series Study ◽

Multiple Sclerosis Patients

Abstract Background Alemtuzumab is an effective disease-modifying therapy (DMT) for highly active multiple sclerosis (MS). However, safety concerns limit its use in clinical practice. Objectives To evaluate the safety of alemtuzumab in a nationwide cohort of Finnish MS patients. Methods In this retrospective case series study, we analyzed the data of all but two MS patients who had received alemtuzumab in Finland until 2019. Data were systematically collected from patient files. Results Altogether 121 patients were identified, most of whom had received previous DMTs (82.6%). Median follow-up time after treatment initiation was 30.3 months and exceeded 24 months in 78 patients. Infusion-associated reactions (IARs) were observed in 84.3%, 57.3%, and 57.1% of patients during alemtuzumab courses 1–3, respectively. Serious adverse events (SAEs) were observed in 32.2% of patients, serious IARs in 12.4% of patients, and SAEs other than IARs in 23.1% of patients. Autoimmune adverse events were observed in 30.6% of patients. One patient died of hemophagocytic lymphohistiocytosis, and one patient died of pneumonia. A previously unreported case of thrombotic thrombocytopenic purpura was documented. Conclusions SAEs were more frequent in the present cohort than in previous studies. Even though alemtuzumab is a highly effective therapy for MS, vigorous monitoring with a long enough follow-up time is advised.

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Tumefactive multiple sclerosis (TMS): A case series of this challenging variant of MS

Multiple Sclerosis and Related Disorders ◽

10.1016/j.msard.2020.102699 ◽

2021 ◽

Vol 48 ◽

pp. 102699

Author(s):

Joseph V. Villarreal ◽

Maria J. Abraham ◽

Joanne Allieza G. Acevedo ◽

Prashant K. Rai ◽

Neeharika Thottempudi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Case Series ◽

Tumefactive Multiple Sclerosis

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Extended dosing of monoclonal antibodies in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/13524585211065711 ◽

2021 ◽

pp. 135245852110657

Author(s):

Zoé LE van Kempen ◽

Alyssa A Toorop ◽

Finn Sellebjerg ◽

Gavin Giovannoni ◽

Joep Killestein

Keyword(s):

Multiple Sclerosis ◽

Monoclonal Antibodies ◽

Treatment Options ◽

Future Research ◽

Therapeutic Drug ◽

Therapeutic Landscape ◽

Anti Cd20 ◽

Dosing Intervals ◽

Care Costs ◽

Review Current

Over the past two decades, treatment options for patients with multiple sclerosis (MS) have increased exponentially. In the current therapeutic landscape, “no evidence of MS disease activity” is within reach in many of our patients. Minimizing risks of complications, improving treatment convenience, and decreasing health care costs are goals that are yet to be reached. One way to optimize MS therapy is to implement personalized or extended interval dosing. Monoclonal antibodies are suitable candidates for personalized dosing (by therapeutic drug monitoring) or extended interval dosing. An increasing number of studies are performed and underway reporting on altered dosing intervals of anti-α4β1-integrin treatment (natalizumab) and anti-CD20 treatment (ocrelizumab, rituximab, and ofatumumab) in MS. In this review, current available evidence regarding personalized and extended interval dosing of monoclonal antibodies in MS is discussed with recommendations for future research and clinical practice.

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The effect of functional limitations and fatigue on the quality of life in people with multiple sclerosis

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2009000500006 ◽

2009 ◽

Vol 67 (3b) ◽

pp. 812-817 ◽

Cited By ~ 22

Author(s):

Leandro Alberto Calazans Nogueira ◽

Felipe Resende Nóbrega ◽

Kátia Nogueira Lopes ◽

Luiz Claudio Santos Thuler ◽

Regina Maria Papais Alvarenga

Keyword(s):

Quality Of Life ◽

Multiple Sclerosis ◽

Functional Limitations ◽

Case Series ◽

Lower Limbs ◽

Case Series Study ◽

Modified Ashworth Scale ◽

Mild Disability ◽

Fatigue Severity

The purpose of this study was to determine the effect of functional limitations and fatigue on the quality of life (QoL) in people with multiple sclerosis (MS). A descriptive case series study at Lagoa Hospital - Rio de Janeiro, Brazil was carried. The main outcome measurements were demographic variables, QoL (SF-36 v.1), disability (EDSS), motor function of the upper limb (Box & Blocks test), Tone (Modified Ashworth Scale), gait (Hauser ambulatory index) and fatigue (Fatigue Severity Scale). Sixty one patients fulfilled the study criteria. The mean age of patients was 39 years and 74% of patients were female. The most of cases presented mild disability (EDSS<3.5). A decrease was found in all domains of QoL. It was found association between physical functioning and the variables of EDSS, fatigue, lower limb tone and gait. Gait, disability, hypertonia of the lower limbs and fatigue negatively affected QoL in people with MS.

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Anti-CD20 therapies decrease humoral immune response to SARS-CoV-2 in patients with multiple sclerosis or neuromyelitis optica spectrum disorders

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2021-326904 ◽

2021 ◽

pp. jnnp-2021-326904

Author(s):

Céline Louapre ◽

Michella Ibrahim ◽

Elisabeth Maillart ◽

Basma Abdi ◽

Caroline Papeix ◽

...

Keyword(s):

Multiple Sclerosis ◽

Neuromyelitis Optica ◽

Seroconversion Rate ◽

Neuromyelitis Optica Spectrum Disorders ◽

Linear Regression Models ◽

Positive Serology ◽

Humoral Immune ◽

Antibody Positivity ◽

Spectrum Disorders ◽

Anti Cd20

BackgroundSARS-CoV-2 seroconversion rate after COVID-19 may be influenced by disease-modifying therapies (DMTs) in patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorders (NMO-SD).ObjectiveTo investigate the seroprevalence and the quantity of SARS-CoV-2 antibodies in a cohort of patients with MS or NMO-SD.MethodsBlood samples were collected in patients diagnosed with COVID-19 between 19 February 2020 and 26 February 2021. SARS-CoV-2 antibody positivity rates and Ig levels (anti-S IgG titre, anti-S IgA index, anti-N IgG index) were compared between DMTs groups. Multivariate logistic and linear regression models were used to estimate the influence of DMTs and other confounding variables on SARS-CoV-2 serological outcomes.Results119 patients (115 MS, 4 NMO, mean age: 43.0 years) were analysed. Overall, seroconversion rate was 80.6% within 5.0 (SD 3.4) months after infection. 20/21 (95.2%) patients without DMT and 66/77 (85.7%) patients on DMTs other than anti-CD20 had at least one SARS-CoV-2 Ig positivity, while this rate decreased to only 10/21 (47.6%) for patients on anti-CD20 (p<0.001). Being on anti-CD20 was associated with a decreased odd of positive serology (OR, 0.07 (95% CI 0.01 to 0.69), p=0.02) independently from time to COVID-19, total IgG level, age, sex and COVID-19 severity. Time between last anti-CD20 infusion and COVID-19 was longer (mean (SD), 3.7 (2.0) months) in seropositive patients compared with seronegative patients (mean (SD), 1.9 (1.5) months, p=0.04).ConclusionsSARS-CoV-2 antibody response was decreased in patients with MS or NMO-SD treated with anti-CD20 therapies. Monitoring long-term risk of reinfection and specific vaccination strategies in this population may be warranted.Trial registration numberNCT04568707.

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