Journal of Neurology, Год журнала: 2024, Номер 271(6), С. 3116 - 3130
Опубликована: Апрель 14, 2024
Abstract Multiple sclerosis (MS) is characterized by progressive neuroinflammation and neurodegeneration from disease onset that, if left untreated, can result in the accumulation of irreversible neurological disability. Early intervention with high-efficacy therapies (HETs) increasingly recognized as best strategy to delay or mitigate progression earliest stages prevent long-term neurodegeneration. Although there growing clinical real-world evidence supporting early HET intervention, foregoing this favor a traditional escalation approach prioritizing lower-efficacy disease-modifying remains common practice. This review explores potential health care professional- patient-related barriers use HETs patients MS United States. Barriers include regulatory reimbursement restrictions; knowledge gaps safety concerns among professionals; various individual, cultural, societal factors affecting patients. Potential strategies for overcoming these encouraging are proposed.
Язык: Английский
Процитировано
8Shifting from the treat-to-target to the early highly effective treatment approach in patients with multiple sclerosis – real-world evidence from Germany
Therapeutic Advances in Neurological Disorders, Год журнала: 2024, Номер 17
Опубликована: Янв. 1, 2024
Background: While evidence highlights the effectiveness of initiating disease-modifying therapy with a high-efficacy medication for multiple sclerosis (MS) patients poor prognostic factors, it remains unclear whether this approach has been adopted by broad range MS providers in Germany yet. Objective: To assess adoption early highly effective treatment (EHT) compared to treat-to-target option escalating efficacy over time based on real-world data. Design: Patient-level pharmacy dispensing data from Permea platform were analysed 2020 2022. Methods: In total, 29,529 beginners (>18 years) included analyse shifts approaches and switching behaviour. Medication classification adhered German Society Neurology guidelines designated fumarates, glatiramer acetate, teriflunomide interferons as low-efficacy category 1 medications; cladribine S1P-modulators medium-efficacy 2 alemtuzumab, natalizumab, ocrelizumab, ofatumumab rituximab (off-label) 3 medications. Results: Our results show that 70.0% redeemed their first prescription medication, 16.3% 13.7% The proportion prescriptions filled shifted 2022 decrease 14.7% drugs an increase 12.5% drugs. 93.2% stayed initially prescribed category. 3.2% 3.7% escalated medication. 3.4% users de-escalated or 2. Conclusion: most individuals started according remained category, there steadily increasing shift towards EHT since 2020. These insights demonstrate that, while not officially recommended guidelines, increasingly adopt approach.
Язык: Английский
Процитировано
5Beyond lines of treatment: embracing early high-efficacy disease-modifying treatments for multiple sclerosis management
Therapeutic Advances in Neurological Disorders, Год журнала: 2024, Номер 17
Опубликована: Янв. 1, 2024
Recent advances in multiple sclerosis (MS) management have shifted perspectives on treatment strategies, advocating for the early initiation of high-efficacy disease-modifying therapies (heDMTs). This perspective review discusses rationale, benefits, and challenges associated with heDMT initiation, reflecting obsolescence traditional "first-line" "second-line" classifications. The article emerges from last update consensus document Spanish Society Neurology MS. During its development, there was a recognized need to further discuss concept lines use heDMTs. Evidence randomized controlled trials real-world studies suggests that leads improved clinical outcomes, including reduced relapse rates, slowed disease progression, decreased radiological activity, especially younger patients or those stages. Despite historical belief heDMTs involve more risks adverse events compared moderate-efficacy DMTs (meDMTs), some reported comparable safety profiles between meDMTs, though long-term data are still lacking. also addresses personalized approach based patient characteristics, prognostic factors, preferences, explores importance therapeutic inertia, highlights evolving landscape international national guidelines increasingly advocate intensive approaches. ensuring access these research establish effectiveness
Язык: Английский
Процитировано
5Disease Modifying Strategies in Multiple Sclerosis: New Rays of Hope to Combat Disability?
Current Neuropharmacology, Год журнала: 2024, Номер 22(8), С. 1286 - 1326
Опубликована: Янв. 25, 2024
Abstract: Multiple sclerosis (MS) is the most prevalent chronic autoimmune inflammatory- demyelinating disorder of central nervous system (CNS). It usually begins in young adulthood, mainly between second and fourth decades life. Usually, clinical course characterized by involvement multiple CNS functional systems different, often overlapping phenotypes. In last decades, remarkable results have been achieved treatment MS, particularly relapsing- remitting (RRMS) form, thus improving long-term outcome for many patients. As deeper knowledge MS pathogenesis respective molecular targets keeps growing, nowadays, several lines disease-modifying treatments (DMT) are available, an impressive change compared to relative poverty options available past. Current management DMTs aimed at reducing relapse frequency, ameliorating symptoms, preventing disability progression. Notwithstanding relevant increase pharmacological RRMS, research now increasingly pointing identify new molecules with high efficacy, progressive forms. Hence, future efforts should be concentrated on achieving a more extensive, if not exhaustive, understanding pathogenetic mechanisms underlying this phase disease order characterize novel therapeutic intervention. The purpose review provide compact overview numerous currently approved innovative approaches, including neuroprotective as anti-LINGO-1 monoclonal antibody cell therapies, effective safe potentially leading cure disease.
Язык: Английский
Процитировано
3Cost-Utility Analysis and Efficiency Frontier of Drugs Available in Brazil for the Treatment of Relapsing-Remitting Multiple Sclerosis
Value in Health Regional Issues, Год журнала: 2025, Номер 48, С. 101092 - 101092
Опубликована: Фев. 20, 2025
Язык: Английский
Процитировано
0Navigating a Paradigm Shift in the Treatment of CNS Demyelinating Diseases in a Middle-Income Country
Multiple Sclerosis and Related Disorders, Год журнала: 2025, Номер 100, С. 106544 - 106544
Опубликована: Май 22, 2025
Язык: Английский
Процитировано
0Early intensive versus escalation treatment in patients with relapsing–remitting multiple sclerosis in Austria
Journal of Neurology, Год журнала: 2024, Номер 271(6), С. 3142 - 3152
Опубликована: Март 2, 2024
Abstract Objectives To compare the effectiveness of early intensive treatment (EIT) versus escalation (ESC) in a nationwide observational cohort almost 1000 people with relapsing–remitting multiple sclerosis (RRMS). Materials and methods The EIT started alemtuzumab (AZM), cladribine (CLAD), fingolimod (FTY), natalizumab (NTZ), ocrelizumab (OCR), or ozanimod (OZA); whereas, ESC was escalated from dimethylfumarate (DMF) teriflunomide (TERI) to AZM, CLAD, FTY, NTZ, OCR, OZA within Austrian MS Treatment Registry. Patients had stay on therapy for at least 3 months up 16 years. included 743 227 RRMS patients. We used multinomial propensity scores inverse probability weighting generalized linear (GLM) Cox proportional hazards models correct bias this non-randomized registry study. Results Estimated mean annualized relapse rates (ARR) were 0.09 0.4 incidence rate ratio (IRR) GLM model relapses showed decreased 78% [IRR = 0.22, 95% CI (0.16–0.30), p < 0.001]. Analyzing time first by regression, hazard (HR) 0.17 [95% (0.13–0.22), 0.001] revealed risk 83% group. Regarding sustained Expanded Disability Status Scale (EDSS) progression 12 weeks, HR 0.55 (0.40–0.76), 45% cohort. Conclusions after DMF TERI higher EDSS compared Therefore, an should be patients active highly disease course.
Язык: Английский
Процитировано
2Infection Risk Associated with High‐Efficacy Disease‐Modifying Agents in Multiple Sclerosis: A Retrospective Cohort Study
Clinical Pharmacology & Therapeutics, Год журнала: 2024, Номер unknown
Опубликована: Ноя. 15, 2024
In patients with multiple sclerosis (MS), infections represent a significant concern, particularly given the immunomodulatory effects of disease‐modifying agents (DMAs). High‐efficacy DMAs (heDMAs) play pivotal role in delaying MS progression, yet their use also raises concerns regarding risk infection. This study aimed to compare infection heDMA and moderate‐efficacy (meDMAs) patients. retrospective cohort involved adult (18–64 years) incident DMA based on 2015–2019 MarketScan Commercial Claims Encounters Database. Patients initiating heDMAs (natalizumab, alemtuzumab, ocrelizumab) or meDMAs (interferon beta‐1a, interferon beta‐1b, fingolimod, teriflunomide, dimethyl fumarate, glatiramer acetate) were included. The outcomes interest comparative overall infection, serious frequently reported types Adjusted hazard ratios (aHR) estimated inverse probability treatment weighting (IPTW) Cox proportional models. Among 10,003 eligible users, 22.92% initiated heDMAs. IPTW‐CPH model revealed that associated higher (aHR: 1.24, 95% confidence interval (CI): 1.06–1.44) urinary tract (UTI; aHR: 1.21, CI: 1.14–1.30). Sensitivity analyses different follow‐up periods yielded consistent findings main analyses. MS, greater UTI compared meDMAs. These suggest need carefully monitor manage optimize MS.
Язык: Английский
Процитировано
2The myths that drive therapeutic inertia in multiple sclerosis: a cost-effectiveness analysis of high-efficacy drugs in Brazil
Arquivos de Neuro-Psiquiatria, Год журнала: 2024, Номер 82(01), С. 001 - 002
Опубликована: Янв. 1, 2024
We read with great interest the article by Hartmann and colleagues, which argued that clinical-radiological paradox was a myth in multiple sclerosis (MS).[1] This critical demystification of adds vital element to our growing understanding importance each new lesion MS. It further underscores necessity for an aggressive treatment approach this disease.
Язык: Английский
Процитировано
1Effects of High Efficacy Multiple Sclerosis Disease Modifying Drugs on the Immune Synapse: A Systematic Review
Current Pharmaceutical Design, Год журнала: 2024, Номер 30(7), С. 536 - 551
Опубликована: Фев. 1, 2024
Background:: Co-signaling and adhesion molecules are important elements for creating immune synapses between T lymphocytes antigen-presenting cells; they positively or negatively regulate the interaction a cell receptor with its cognate antigen, presented by major histocompatibility complex. Objectives:: We conducted systematic review on effects of High Efficacy Disease Modifying Drugs (HEDMDs) Multiple Sclerosis (MS) co-signaling that form synapse. Methods:: searched EMBASE, MEDLINE, other sources to identify clinical preclinical reports HEDMDs participate in formation patients MS autoimmune disorders. included cladribine tablets, anti- CD20 monoclonal antibodies, S1P modulators, inhibitors Bruton’s Tyrosine Kinase, natalizumab. Results:: In 56 eligible among 7340 total publications, limited relevant evidence was uncovered. Not all have been studied relation every HEDMD, more data being available anti-CD20 antibodies (that affect CD80, CD86, GITR TIGIT), tablets (affecting CD28, CD40, ICAM-1, LFA-1) modulators ICAM-1 less Natalizumab LFA-1, VLA-4) Alemtuzumab CTLA-4). Conclusion:: The puzzle HEDMD synapse is far from complete. suggests distinguishing differences exist drugs worth pursuing further.
Язык: Английский
Процитировано
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