Extended dosing of monoclonal antibodies in multiple sclerosis

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.

Anti-CD20 monoclonal antibodies in multiple sclerosis

2016 ◽  
Vol 17 (4) ◽  
pp. 359-371 ◽  
Author(s):  
Irene Moreno Torres ◽  
Antonio García-Merino
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibodies ◽  
Anti Cd20

scholarly journals Vaccine Hesitancy in Patients With Multiple Sclerosis

2021 ◽  
Vol 8 (3) ◽  
pp. e991
Author(s):  
Lara Diem ◽  
Christoph Friedli ◽  
Andrew Chan ◽  
Anke Salmen ◽  
Robert Hoepner
Keyword(s):  
Multiple Sclerosis ◽  
Pneumococcal Vaccination ◽  
Standard Of Care ◽  
University Hospital ◽  
Vaccine Hesitancy ◽  
Public Health Issue ◽  
Future Research ◽  
Medical Chart Review ◽  
History Of ◽  
Anti Cd20

ObjectiveVaccine hesitancy is a complex public health issue referring to concerns about safety, efficacy, or need for vaccination. Using pneumococcal vaccination, which is recommend in anti-CD20–treated multiple sclerosis (MS) patients, as a model, we assessed vaccination behavior in patients with MS to prepare for the upcoming SARS-CoV-2 vaccination challenge.MethodsBy a medical chart review, we retrospectively identified patients with MS treated with ocrelizumab at the University Hospital Bern in 2018–2020. Pneumococcal vaccination was discussed with the patients during clinical visits and highlighted in the after-visit summary addressed to the general practitioner before ocrelizumab initiation as part of our clinical standard of care.ResultsPneumococcal vaccination was performed in 71/121 (58.7%) of patients, and 50/121 (41.3%) patients were not vaccinated. Patients who did not get a pneumococcal vaccination were younger (no vaccination vs vaccination; mean [95% CI] 40.1 [36.1–44.1] vs 45.4 [41.9–48.8], p = 0.028) and had more frequently a relapsing remitting disease course (no vaccination vs vaccination, n [%]; 43/50 [86.0%] vs 49/71 [69.0%], p = 0.031). Furthermore, patients who did not get vaccination had more frequently a history of comorbid psychiatric disorder (no vaccination vs vaccination, n (%); 12/50 [24.0] vs 7/71 [9.8], p = 0.035).ConclusionOur study demonstrated that in our single-center cohort, 41.3% of patients with MS do not get the recommended pneumococcal vaccination. Future research should focus on vaccine hesitancy in the vulnerable cohort of patients with MS to improve the safety of MS immunotherapies.

Expanding the armamentarium for chronic lymphocytic leukemia: A review of novel agents in the management of chronic lymphocytic leukemia

2016 ◽  
Vol 23 (7) ◽  
pp. 502-517 ◽  
Author(s):  
Bernard L Marini ◽  
Lisa Samanas ◽  
Anthony J Perissinotti
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Treatment Options ◽  
Cell Receptor ◽  
The United States ◽  
Lymphocytic Leukemia ◽  
Novel Agents ◽  
Great Promise ◽  
Therapeutic Landscape ◽  
Excellent Activity ◽  
Anti Cd20

Treatment options for chronic lymphocytic leukemia, the most common leukemia in the United States, have expanded rapidly in recent years. While traditional chemoimmunotherapy still remains a mainstay for young, fit patients, a number of novel targeted therapies have emerged that have changed the therapeutic landscape. Two innovative anti-CD20 monoclonal antibodies, obinutuzumab and ofatumomamab, have demonstrated activity in chronic lymphocytic leukemia and represent well-tolerated options in upfront management of elderly patients or in those with significant comorbidities. Agents targeting the B-cell receptor pathway, ibrutinib and idelalisib, have excellent activity in chronic lymphocytic leukemia, particularly in those patients with 17p deletions, in which responses to chemoimmunotherapy are traditionally dismal. Venetoclax (ABT-199), the recently FDA-approved BCL2 inhibitor, as well as several other agents and therapy combinations in the pipeline offer great promise for patients with chronic lymphocytic leukemia, particularly in the relapsed/refractory setting. This article comprehensively reviews the data for novel agents in chronic lymphocytic leukemia, including the pharmacology of therapies, unique toxicities, and other practical management considerations for clinicians.

Anti-CD20 Monoclonal Antibodies for Relapsing and Progressive Multiple Sclerosis

CNS Drugs ◽  
2020 ◽  
Vol 34 (3) ◽  
pp. 269-280 ◽  
Author(s):  
Finn Sellebjerg ◽  
Morten Blinkenberg ◽  
Per Soelberg Sorensen
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibodies ◽  
Progressive Multiple Sclerosis ◽  
Anti Cd20

scholarly journals A Milestone in Multiple Sclerosis Therapy: Monoclonal Antibodies Against CD20—Yet Progress Continues

2021 ◽  
Author(s):  
Esther S. Frisch ◽  
Roxanne Pretzsch ◽  
Martin S. Weber
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibodies ◽  
B Cells ◽  
B Cell ◽  
Current Knowledge ◽  
Disease Onset ◽  
Chronic Inflammatory Disease ◽  
Targeting Therapy ◽  
Long Term Treatment ◽  
Anti Cd20

AbstractMultiple sclerosis (MS), which is a chronic inflammatory disease of the central nervous system, still represents one of the most common causes of persisting disability with an early disease onset. Growing evidence suggests B cells to play a crucial role in its pathogenesis and progression. Over the last decades, monoclonal antibodies (mabs) against the surface protein CD20 have been intensively studied as a B cell targeting therapy in relapsing MS (RMS) as well as primary progressive MS (PPMS). Pivotal studies on anti-CD20 therapy in RMS showed remarkable clinical and radiological effects, especially on acute inflammation and relapse biology. These results paved the way for further research on the implication of B cells in the pathogenesis of MS. Besides controlling relapse development in RMS, ocrelizumab (OCR) also showed clinical benefits in patients with PPMS and became the first approved drug for this disease course. In this review, we provide an overview of the current anti-CD20 mabs used or tested for the treatment of MS—namely rituximab (RTX), OCR, ofatumumab (OFA), and ublituximab (UB). Besides their effectiveness, we also discuss possible limitations and safety concerns especially in regard to long-term treatment, both for this class of drugs overall as well as for each anti-CD20 mab individually. Additionally, we elucidate to what extent anti-CD20 therapy may alter the function of other immune cells, both directly or indirectly. Finally, we cover the current knowledge on repopulation of CD20+ cells after cessation of anti-CD20 treatment and discuss future aspirations towards alternative, further developed B cell silencing therapies.

scholarly journals Impact of Disease-Modifying Treatments of Multiple Sclerosis on Anti–SARS-CoV-2 Antibodies

2021 ◽  
Vol 8 (5) ◽  
pp. e1055
Author(s):  
Kévin Bigaut ◽  
Laurent Kremer ◽  
Thibaut Fabacher ◽  
Livia Lanotte ◽  
Marie-Celine Fleury ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibodies ◽  
Recurrent Infection ◽  
Humoral Response ◽  
Interferon Β ◽  
Igg Index ◽  
Disease Modifying ◽  
Anti Cd20 ◽  
Class Iv

ObjectiveTo compare the humoral response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with multiple sclerosis (MS) receiving different disease-modifying treatments (DMTs).MethodsPatients with MS with coronavirus disease 2019 (COVID-19) and available anti–SARS-CoV-2 serology were included. The primary endpoint was the anti–SARS-CoV-2 immunoglobulin G (IgG) index. The multivariate analysis was adjusted for COVID-19 severity, SARS-CoV-2 PCR result, and the time between COVID-19 onset and the serology.ResultsWe included 61 patients with available IgG index. The IgG index was lower in patients with fingolimod or anti-CD20 monoclonal antibodies compared with patients without treatment (p < 0.01), patients with interferon β-1a or glatiramer (p < 0.01), and patients with another DMT (p = 0.01). The IgG index was correlated with the time between COVID-19 onset and serology (r = −0.296 [−0.510; −0.0477], p = 0.02).ConclusionsHumoral response after COVID-19 was lower in patients with MS with fingolimod or anti-CD20 mAb. These patients could therefore be at risk of recurrent infection and could benefit from anti–SARS-CoV-2 vaccination. The humoral response after vaccination and the delay before vaccination need to be evaluated.Classification of EvidenceThis study provides Class IV evidence that patients treated with fingolimod or anti-CD20 monoclonal antibodies for MS have a lower humoral response after COVID-19 compared with patients without DMTs or with another DMTs.

scholarly journals Anti-CD20 Agents for Multiple Sclerosis: Spotlight on Ocrelizumab and Ofatumumab

2020 ◽  
Vol 10 (10) ◽  
pp. 758
Author(s):  
Despoina Florou ◽  
Maria Katsara ◽  
Jack Feehan ◽  
Efthimios Dardiotis ◽  
Vasso Apostolopoulos
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibody ◽  
B Cells ◽  
Treatment Options ◽  
T Helper ◽  
Positive Effects ◽  
Cd20 Antibody ◽  
Anti Cd20 ◽  
Disease Modifying Treatment ◽  
Small Clinical Trials

Until recently, in the pathogenesis of Multiple Sclerosis (MS), the contribution of B cells has been largely underestimated, and the disease was considered a T-cell-mediated disorder. However, newer evidence shows that B cells play a crucial role in the pathogenesis of MS via antigen-driven autoantibody responses and through the cross regulation of T-helper cells. As B cells express the surface molecule CD20 at all points of differentiation, it provides a specific target for monoclonal antibodies, and the development and clinical testing of anti-CD20 antibody treatments for MS have been successful. After some observations, some small clinical trials found positive effects for the first anti-CD20 therapeutic rituximab in MS; newer agents have been specifically evaluated, resulting in the development of ocrelizumab and ofatumumab. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, was approved in March 2017 by the Food and Drug Administration (FDA) and is also the first proven therapy to reduce disability progression in primary progressive MS. This is particularly significant considering that disease-modifying treatment options are few for both primary and secondary progressive MS. Ofatumumab, a fully human anti-CD20 monoclonal antibody, that binds a distinct epitope, has been further investigated in phase 3 trials for relapsing forms of MS. In this review, we discuss in detail these two anti-CD20 agents and their advent for treatment of MS.

scholarly journals Multiple Sclerosis in Children: Current and Emerging Concepts

2020 ◽  
Vol 40 (02) ◽  
pp. 192-200
Author(s):  
J. Nicholas Brenton ◽  
Ryan Kammeyer ◽  
Lauren Gluck ◽  
Teri Schreiner ◽  
Naila Makhani
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
International Collaboration ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Future Research ◽  
Imaging Findings ◽  
The Past ◽  
New Treatment ◽  
Made In

AbstractMultiple sclerosis is being increasingly recognized and diagnosed in children. In the past several years, advances have been made in diagnosing multiple sclerosis in children, identifying new genetic and environmental risk factors, delineating underlying immunobiology, characterizing imaging findings, and implementing new treatment strategies. In this review, we discuss these advances. Future research into the determinants of multiple sclerosis in children and into new treatment options will be aided by continued international collaboration.

scholarly journals Clinical outcome measures for progressive MS trials

2017 ◽  
Vol 23 (12) ◽  
pp. 1627-1635 ◽  
Author(s):  
Daniel Ontaneda ◽  
Jeffrey A Cohen ◽  
Maria Pia Amato
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Clinical Outcome ◽  
Outcome Measures ◽  
Treatment Options ◽  
Unmet Need ◽  
Screening Tests ◽  
Future Research ◽  
Neuroprotective Effects ◽  
Patient Reported

Treatment options for progressive multiple sclerosis remain the main unmet need of the field. As the understanding of multiple sclerosis (MS) pathogenesis improves, new pathways and molecules will be tested for potential reparative, remyelinating, or neuroprotective effects. The clinical outcomes used will determine successful demonstration of beneficial treatment effects to regulatory agencies, clinicians, and persons with MS. This review focuses on clinical outcome measures including the Expanded Disability Status Scale, Multiple Sclerosis Functional Composite, and novel composite measures of disability. The paper also covers cognitive outcomes and screening tests for use in clinical trials. The growing importance of patient-reported outcomes and their suitability for clinical trials is also presented. The review aims to create consensus in regard to these topics and suggestions for future research.

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