Cytokine Secretion Dynamics of Isolated PBMC after Cladribine Exposure in RRMS Patients DOI Open Access
Rodica Bălașa, Smaranda Maier, Adina Huţanu

и другие.

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(18), С. 10262 - 10262

Опубликована: Сен. 6, 2022

Cladribine (CLD) treats multiple sclerosis (MS) by selectively and transiently depleting B T cells with a secondary long-term reconstruction of the immune system. This study provides evidence CLD’s immunomodulatory role in peripheral blood mononuclear (PBMCs) harvested from 40 patients untreated relapsing-remitting MS (RRMS) exposed to CLD. We quantified cytokine secretion PBMCs isolated density gradient centrifugation Ficoll−Paque using xMAP technology on FlexMap 3D analyzer highly sensitive multiplex immunoassay kit. The PBMC secretory profile was evaluated without CLD exposure. RRMS for ≤12 months had significantly higher IL-4 but lower IFN-γ TNF-α after >12 altered inflammatory ratios toward an anti-inflammatory increased decreased induced nonsignificant changes IL-17 both groups. Our findings reaffirm effect that induces phenotype.

Язык: Английский

Updates and Advances in Multiple Sclerosis Neurotherapeutics DOI Creative Commons
Moein Amin, Carrie M. Hersh

Neurodegenerative Disease Management, Год журнала: 2022, Номер 13(1), С. 47 - 70

Опубликована: Окт. 31, 2022

The multiple sclerosis (MS) neurotherapeutic landscape is rapidly evolving. New disease-modifying therapies (DMTs) with improved efficacy and safety, in addition to an expanding pipeline of agents novel mechanisms, provide more options for patients MS. While treatment MS neuroinflammation well tailored the existing DMT armamentarium, concerted efforts are currently underway identifying neuropathological targets drug discovery progressive There also ongoing research develop remyelination neuroprotection. Further insights needed guide initiation sequencing as determine role autologous stem cell transplantation relapsing This review provides a summary these updates.

Язык: Английский

Процитировано

102
Cladribine Tablets for Relapsing–Remitting Multiple Sclerosis: A Clinician’s Review DOI Creative Commons
Gavin Giovannoni, Joela Mathews

Neurology and Therapy, Год журнала: 2022, Номер 11(2), С. 571 - 595

Опубликована: Март 23, 2022

Multiple sclerosis (MS) is a chronic neurodegenerative disease characterized by inflammation and demyelination for which there currently no cure; therefore, the aim of therapy to reduce risk relapse disability progression. The treatment options MS have increased greatly in recent years with development several disease-modifying therapies (DMTs) advent immune reconstitution (IRT). IRTs are administered short-dosing periods produce long-term effects on system. Treatment an IRT based 3Rs: reduction, repopulation, lymphocytes, leads restoration effector functions. Cladribine tablets represent selective, high-efficacy, oral form patients that targets lymphocytes spares innate cells. Patients require only two weekly courses, each course comprising weeks, Years 1 2; cladribine associated lower monitoring burden than many other DMTs, while short dosing can help improve adherence. This review provides overview offers clinician's perspective current landscape, focus practical advice management undergoing most evidence available, including risks COVID-19 recommendations vaccination MS.

Язык: Английский

Процитировано

42
Predictors of Cladribine Effectiveness and Safety in Multiple Sclerosis: A Real-World, Multicenter, 2-Year Follow-Up Study DOI Creative Commons
Maria Petracca, Serena Ruggieri,

Elena Barbuti

и другие.

Neurology and Therapy, Год журнала: 2022, Номер 11(3), С. 1193 - 1208

Опубликована: Июнь 2, 2022

Cladribine administration has been approved for the treatment of relapsing-remitting multiple sclerosis (MS) in 2017; thus, data on cladribine a real-world setting are still emerging.We report effectiveness, safety profile, and response predictors 243 patients with MS followed at eight tertiary centers. Study outcomes were: (1) No Evidence Disease Activity-3 (NEDA-3) status its components (absence clinical relapses, MRI activity, sustained disability worsening); (2) development grade III/IV lymphopenia. The relationship between baseline features selected was tested via multivariate logistic models.Of subjects included study (66.5% female, age 34.2 ± 10 years, disease duration 6.6 9.6 years), 64% showed NEDA-3 median follow-up (22 months). Patients higher number previous treatments had lower probability to retain [odds ratio (OR) 0.64, 95% confidence interval (CI) 0.41-0.98, p = 0.04] were more prone experience relapses (OR 1.6, CI 1-2.6, 0.04). presence active lesions associated magnetic resonance imaging (MRI) activity 1.92, 1.04-3.55, rate year prior start risk developing worsening 2.95% 1-4.2, Lymphopenia over lymphocyte count 0.998, 0.997-0.999, 0.01).In this large cohort, we confirm about effectiveness provide information that might inform therapeutic choices.

Язык: Английский

Процитировано

30
Finnish multiple sclerosis patients treated with cladribine tablets: a nationwide registry study DOI Creative Commons
Ilkka Rauma, Matias Viitala, Hanna Kuusisto

и другие.

Multiple Sclerosis and Related Disorders, Год журнала: 2022, Номер 61, С. 103755 - 103755

Опубликована: Март 20, 2022

Cladribine tablets for adult patients with highly active relapsing multiple sclerosis (MS) have been available in Finland since 2018. Real-world data from different genetic and geographical backgrounds are needed to complement clinical trials.We investigated the use of cladribine a non-interventional cohort study, based on real-world nationwide Finnish MS registry. All eligible who had initiated treatment 2018-2020 were included. Descriptive analyses outcomes conducted using summary statistics. Time-dependent endpoints analyzed cumulated events analysis 1-Kaplan-Meier estimates curves. Subgroups separately according number previous disease-modifying therapies (DMTs) most common last preceding therapies.Data 179 analyzed. Median follow-up time was 19.0 months (interquartile range [IQR] 12.0-26.2). Of 134 followed at least 12 months, 112 (83.6%) remained relapse-free during follow-up. Mean annualized relapse rate (ARR) 1.0 (standard deviation [SD] 0.89) baseline, 0.1 (SD 0.30) Patients two or more DMTs shorter first (median 2.5 IQR 0.6-9.3) when compared 0-1 11.4 8.7-13.1) (p=0.013). After excluding switching fingolimod (n=33), statistically significant difference no longer observed between groups (p=0.252). Adverse (AEs) reported 30 (16.8%). The frequent AE headache (n=14, 7.8%). One patient (0.6%) died cardiac arrest. Discontinuation nine (5.0%).The mean ARR this similar what has trials. Approximately half used before tablets. These DMTs, mostly driven by early relapses fingolimod.

Язык: Английский

Процитировано

29
Real-world experience of cladribine treatment in relapsing-remitting multiple sclerosis: A Danish nationwide study DOI Creative Commons
Per Soelberg Sørensen, Luigi Pontieri,

Hanna Joensen

и другие.

Multiple Sclerosis and Related Disorders, Год журнала: 2022, Номер 70, С. 104491 - 104491

Опубликована: Дек. 28, 2022

Язык: Английский

Процитировано

23
The Compelling Role of Brain‐Derived Neurotrophic Factor Signaling in Multiple Sclerosis: Role of BDNF Activators DOI Creative Commons
Hayder M. Al‐kuraishy, Ghassan M. Sulaiman, Hamdoon A. Mohammed

и другие.

CNS Neuroscience & Therapeutics, Год журнала: 2024, Номер 30(12)

Опубликована: Дек. 1, 2024

Brain-derived neurotrophic factor (BDNF) is a neurotrophin, acting as signal and neuromodulator in the central nervous system (CNS). BDNF synthesized from its precursor proBDNF within CNS peripheral tissues. Through activation of NTRK2/TRKB (neurotrophic receptor tyrosine kinase 2), promotes neuronal survival, synaptic plasticity, growth, whereas it inhibits microglial release pro-inflammatory cytokines. dysregulated different neurodegenerative diseases depressions. However, there major controversy concerning levels stages multiple sclerosis (MS). Therefore, this review discusses potential role signaling MS, how modulators affect pathogenesis outcomes disease.

Язык: Английский

Процитировано

5
Safety and efficacy of cladribine in multiple sclerosis: a systematic review and meta-analysis DOI Open Access
Fardin Nabizadeh,

Mobin Mohamadi,

Shayan Rahmani

и другие.

Neurological Sciences, Год журнала: 2023, Номер 44(9), С. 3045 - 3057

Опубликована: Апрель 17, 2023

Язык: Английский

Процитировано

11
The relative risk of infection in people with multiple sclerosis using disease-modifying treatment: a systematic review of observational studies DOI Creative Commons
Melissa Wing Yee Leung, E.M.W. van de Garde, Bernard M.J. Uitdehaag

и другие.

Neurological Sciences, Год журнала: 2025, Номер unknown

Опубликована: Фев. 8, 2025

Язык: Английский

Процитировано

0
Real-world evidence for cladribine tablets in multiple sclerosis: further insights into efficacy and safety DOI Creative Commons
Tobias Moser, Tjalf Ziemssen, Johann Sellner

и другие.

Wiener Medizinische Wochenschrift, Год журнала: 2022, Номер 172(15-16), С. 365 - 372

Опубликована: Апрель 22, 2022

Summary Cladribine (CLAD) is a purine nucleoside analog approved in tablet form to treat highly active multiple sclerosis (MS). CLAD tablets are the first oral therapy with an infrequent dosing schedule, administered two annual treatment courses, each divided into cycles comprising 4–5 days of treatment. The efficacy and safety have been verified randomized controlled clinical trials. Clinical observational studies performed more representative populations over extended periods, thus provide valuable complementary insights. Here, we summarize available evidence for from post-marketing trials, including observational, four long-term extensions, comparative studies. patients setting differed cohort recruited pivotal phase III trials regarding demographics MS-related disability. limited number small cohorts corroborate disease-modifying capacity report on durable benefit after periods. Skin-related adverse events were common focusing aspects. In addition, single cases CLAD-associated autoimmune reported. Lastly, appear safe COVID-19 concerns, mount robust humoral immune response SARS-CoV‑2 vaccination. We conclude that current real-world as reconstitution MS based population distinct Further research should advance understanding disease control periods mitigation events.

Язык: Английский

Процитировано

16
Real-World Retrospective Analysis of Alemtuzumab Outcomes in Relapsing-Remitting Multiple Sclerosis: The LEMCAM Study DOI Creative Commons
Lucienne Costa‐Frossard, Virginia Meca‐Lallana, Andrés Labiano-Fontcuberta

и другие.

CNS Drugs, Год журнала: 2024, Номер 38(3), С. 231 - 238

Опубликована: Фев. 28, 2024

Alemtuzumab is a high-efficacy treatment approved for relapsing-remitting multiple sclerosis (RRMS). Although clinical trials and observational studies are consistent in showing its efficacy manageable safety profile, further under practice conditions needed to support use. The aim of this retrospective study was evaluate the effectiveness alemtuzumab add current real-world evidence on drug. A cohort 115 adult patients with RRMS treated between 2014 2020 retrospectively followed up five centers Spain. Analysis included annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW), improvement (CDI), radiological activity, no disease activity (NEDA-3), signals. Given different follow-up periods among participants, ARR calculated using person-years method. CDI defined as ≥ 1.0-point decrease Expanded Disability Status Scale (EDSS) score assessed baseline EDSS 2.0 6 months apart. CDW increase 1.0 (≥ 1.5 if = 0), decreased from 1.9 (95% confidence interval 1.60–2.33) year prior initiation 0.28 (0.17–0.37) after 1 (87% reduction), 0.22 (0.13–0.35) second year. Over entire period, 0.24 (0.18–0.30). At 1, 75% showed signs magnetic resonance imaging (MRI) 70% at 5. One percent experienced 2.6% 2, 7.4% 3, over years 4 total 7.7% achieved 3.6% maintained it 3 4. Most annual NEDA-3: 72%; 79%; 80%; 4, 89%; 5, 75%. Infusion-related reactions were observed 95% infections 74%. Thyroid disorders occurred 30% patients, only three developed immune thrombocytopenia. No cases progressive multifocal leukoencephalopathy reported. This shows that reduced practice, many achieving sustaining NEDA-3 time. profile previous findings, new or unexpected signals observed. As an study, main limitation not having all variables comprehensively available should be considered when interpreting results.

Язык: Английский

Процитировано

3