Drugs Targeting CD20 in Multiple Sclerosis: Pharmacology, Efficacy, Safety, and Tolerability

Drugs, Journal Year: 2024, Volume and Issue: 84(3), P. 285 - 304

Published: March 1, 2024

Currently, there are four monoclonal antibodies (mAbs) that target the cluster of differentiation (CD) 20 receptor available to treat multiple sclerosis (MS): rituximab, ocrelizumab, ofatumumab, and ublituximab. B-cell depletion therapy has changed therapeutic landscape MS through robust efficacy on clinical manifestations MRI lesion activity, currently anti-CD20 mAb therapies for use in a cornerstone highly effective disease-modifying treatment. Ocrelizumab is only with regulatory approval primary progressive MS. There few data regarding relative these therapies, though several trials ongoing. Safety concerns applicable this class therapeutics relate primarily immunogenicity mechanism action, include infusion-related or injection-related reactions, development hypogammaglobulinemia (leading increased infection malignancy risk), decreased vaccine response. Exploration alternative dose/dosing schedules might be an strategy mitigating risks. Future biosimilar medications make more readily available. Although have led significant improvements disease outcomes, CNS-penetrant still needed effectively address compartmentalized inflammation thought play important role disability progression.

Language: Английский

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Comparing ocrelizumab to interferon/glatiramer acetate in people with multiple sclerosis over age 60

Journal of Neurology Neurosurgery & Psychiatry, Journal Year: 2024, Volume and Issue: 95(8), P. 767 - 774

Published: March 7, 2024

Background Ongoing controversy exists regarding optimal management of disease modifying therapy (DMT) in older people with multiple sclerosis (pwMS). There is concern that the lower relapse rate, combined a higher risk DMT-related infections and side effects, may alter risk-benefit balance pwMS. Given lack pwMS above age 60 randomised controlled trials, comparative efficacy high-efficacy DMTs such as ocrelizumab has not been shown We aimed to evaluate effectiveness ocrelizumab, DMT, versus interferon/glatiramer acetate (IFN/GA) over 60. Methods Using data from MSBase registry, this multicentre cohort study included who switched or started on IFN/GA. analysed disability outcomes after balancing covariates using an inverse probability treatment weighting (IPTW) method. Propensity scores were obtained based age, country, duration, sex, baseline Expanded Disability Status Scale, prior relapses (all-time, 12 months 24 months) DMT exposure (overall number DMTs). After weighting, all balanced. Primary time first annualised rate (ARR). Secondary 6-month confirmed progression (CDP) improvement (CDI). Results A total 248 participants received while 427 The IPTW-weighted ARR for was 0.01 0.08 ratio 0.15 (95% CI 0.06 0.33, p<0.001) compared On Cox regression models, HR 0.13 0.05 0.26, p<0.001). hazard significantly reduced users 5 IFN/GA users. However, two groups did differ CDP CDI 3.57 years. Conclusion In pwMS, effectively Overall activity low. This adds valuable real-world informed decision making Our also confirms there benefit MS, given existence clear differential effect between group.

Language: Английский

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Acute Clinical Events Identified as Relapses With Stable Magnetic Resonance Imaging in Multiple Sclerosis

JAMA Neurology, Journal Year: 2024, Volume and Issue: 81(8), P. 814 - 814

Published: July 1, 2024

Understanding the association between clinically defined relapses and radiological activity in multiple sclerosis (MS) is essential for patient treatment therapeutic development. To investigate clinical events identified as but not associated with new T2 lesions or gadolinium-enhanced T1 on brain spinal cord magnetic resonance imaging (MRI). This multicenter observational cohort study was conducted January 2015 June 2023. Data were extracted 8, 2023, from French MS registry. All reported patients relapsing-remitting included if MRI performed within 12 24 months before event, respectively, 50 days thereafter gadolinium injection. Events classified active (RAM) a lesion appeared acute stable (ACES) otherwise. Factors ACES investigated; RAM compared regarding Expanded Disability Status Scale (EDSS) course, relapse rate, confirmed disability accrual (CDA), relapse-associated worsening (RAW), progression independent of (PIRA), transition to secondary progressive (SP) MS, rates under each disease-modifying therapy (DMT) estimated. Among 31 885 events, 637 608 (493 [77.4%] female; mean [SD] age, 35.8 [10.7] years) included. accounted 166 (26.1%) more likely receiving highly effective DMTs, those longer disease duration (odds ratio [OR], 1.04; 95% CI, 1.01-1.07), presenting fatigue (OR, 2.14; 1.15-3.96). significant EDSS score increases, lower than found RAM. Before index experienced significantly higher (relative rate [RR], 1.21; 1.01-1.46), CDA (hazard [HR], 1.54; 1.13-2.11), RAW (HR, 1.72; 1.20-2.45). Patients at greater risk SP 2.58; 1.02-6.51). Although decreased DMTs according their expected efficacy, across DMTs. The findings this introduce concept which one-fourth relapses.

Language: Английский

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Rituximab for people with multiple sclerosis

Cochrane library, Journal Year: 2025, Volume and Issue: 2025(3)

Published: March 11, 2025

Language: Английский

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EARLY EXTENDED INTERVAL DOSING OF RITUXIMAB IN MULTIPLE SCLEROSIS: A COMPARATIVE COHORT STUDY ON EFFICACY AND SAFETY

Multiple Sclerosis and Related Disorders, Journal Year: 2025, Volume and Issue: unknown, P. 106400 - 106400

Published: March 1, 2025

Language: Английский

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Immunotherapy for hypertensive end-organ damage: a new therapeutic strategy

Essays in Biochemistry, Journal Year: 2025, Volume and Issue: 00(00)

Published: March 25, 2025

Hypertension represents a highly prevalent chronic condition and stands among the foremost contributors to premature mortality on global scale. Its etiopathogenesis is intricate multifaceted, being shaped by diverse array of elements such as age, genetic predisposition, activation neuroendocrine apparatus. Mounting evidence has shed light significant part that autoimmune responses play in hypertension ensuing damage end organs. Virtually all varieties immune cells, spanning both innate adaptive compartments, exhibit close correlation with progression hypertension. These cells infiltrate kidney vascular mesenchyme, subsequently discharging potent cytokines, reactive oxygen species, metalloproteinases. This cascade events can affect functionality local blood vessels potentially precipitate adverse structural functional alterations crucial organs like heart kidney. In recent times, management end-organ emerged pivotal scientific focus. A multitude researchers are actively engaged probing efficacious intervention regimens, which immunotherapy strategies hold considerable promise anticipation prospective avenue.

Language: Английский

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Choosing initial MS therapy; personal, disease, and medication factors

Neurotherapeutics, Journal Year: 2025, Volume and Issue: unknown, P. e00582 - e00582

Published: April 1, 2025

Language: Английский

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Efficacy of ocrelizumab versus rituximab in patients with relapsing-remitting multiple sclerosis

Acta Neurologica Belgica, Journal Year: 2025, Volume and Issue: unknown

Published: April 12, 2025

Language: Английский

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CD70 recruitment to the immunological synapse is dependent on CD20 in B cells

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(16)

Published: April 15, 2025

CD20 is a four-transmembrane protein expressed at the surface of B cells from late pro-B to memory cells, with exception plasma cells. Its expression pattern makes it an attractive therapeutic target for different cell malignancies and autoimmune diseases. Despite clinical success CD20-targeting antibodies, biology still not well understood. We investigated binding partners in membrane human using immunoprecipitation followed by mass spectrometry analysis. identified molecular interaction between CD70 CD20, confirmed this proximity ligation assays. CD20–CD70 spatiotemporal colocalization was validated high-resolution microscopy. Cell found be enhanced upon overexpression, suggesting role stabilizing membrane. Moreover, we observed impaired B-T synapse formation defective recruitment immunological absence CD20. Impaired deleting primary analysis CD20-deficient patient. Finally, CD20-deletion resulted diminished T activation cytokine secretion. Together, study demonstrates that interacts membrane, required immune consequent activation.

Language: Английский

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Autoimmune neuro-ophthalmic disorders: pathophysiologic mechanisms and targeted biologic therapies

Expert Opinion on Biological Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: April 29, 2025

Autoimmune neuro-ophthalmic disorders encompass a diverse array of conditions, including thyroid eye disease (TED), myasthenia gravis (MG), optic neuropathy due to giant cell arteritis (GCA), and neuritis related multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD) myelin oligodendrocyte glycoprotein antibody-associated (MOGAD). While traditional treatments have shown efficacy in managing symptoms, the rapid emergence biologic therapies has brought forth new avenues for targeted intervention, revolutionizing treatment approaches these conditions. This review provides an overview pathophysiologic pathways FDA-approved utilized management autoimmune disorders. We explore therapeutic disorders, IGF-1 R antagonism, IL-6 inhibition, complement FcRn targeting, B-cell depletion T-cell modulation. Literature from clinical trials, observational studies, meta-analyses through 2024 was evaluated assess efficacy, safety, long-term outcomes. Biologic represent significant advancement offering with improved safety profiles compared treatments. Ongoing developments biomarker identification delivery systems suggest increasingly personalized approach treatment. Future advances will likely focus on optimizing patient selection, reducing costs, improving accessibility, developing novel targets.

Language: Английский

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