Effectiveness and safety profile of cladribine in an Italian real-life cohort of relapsing–remitting multiple sclerosis patients: a monocentric longitudinal observational study

Journal of Neurology, Год журнала: 2023, Номер 270(7), С. 3553 - 3564

Опубликована: Апрель 7, 2023

Abstract Introduction Cladribine is approved for the treatment of active relapsing MS (RRMS), but its positioning in therapeutic scenario still needs to be fully elucidated. Methods This a monocentric, observational, real-world study on RRMS patients treated with cladribine. Relapses, magnetic resonance imaging (MRI) activity, disability worsening, and loss no-evidence-of-disease-activity-3 (NEDA-3) status were assessed as outcomes. White blood cell, lymphocyte counts side effects also evaluated. Patients analyzed overall subgroups according last before The relationship between baseline characteristics outcomes was tested identify predictors response. Results Among 114 included, 74.9% NEDA-3 at 24 months. We observed reduction relapses MRI along stabilization disability. A higher number gadolinium-enhancing lesions only risk factor during follow-up. more efficacious switchers from first-line therapies or naïves. Grade I lymphopenia frequent month 3 15. No grade IV cases observed. Independent III lower count previous treatments. Sixty-two presented least one effect globally 111 adverse events recorded, none them serious. Conclusions Our confirms data cladribine effectiveness safety. effective when placed early algorithm. Real-world larger populations longer follow-up are needed confirm our findings.

Язык: Английский

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No Evidence of Disease Activity (NEDA) as a Clinical Assessment Tool for Multiple Sclerosis: Clinician and Patient Perspectives [Narrative Review]

Neurology and Therapy, Год журнала: 2023, Номер 12(6), С. 1909 - 1935

Опубликована: Окт. 11, 2023

The emergence of high-efficacy therapies for multiple sclerosis (MS), which target inflammation more effectively than traditional disease-modifying therapies, has led to a shift in MS management towards achieving the outcome assessment known as no evidence disease activity (NEDA). most common NEDA definition, termed NEDA-3, is composite three related measures activity: clinical relapses, disability progression, and radiological activity. been frequently used endpoint trials, but there growing interest its use an tool help patients healthcare professionals navigate treatment decisions clinic. Raising awareness about may therefore clinicians make informed around improve overall care. This review aims explore potential utility decision-making by summarizing literature on current context expanding landscape. We identify challenges practice detail proposed amendments, such inclusion alternative outcomes biomarkers, broaden information captured NEDA. These themes are further illustrated with real-life perspectives experiences our two patient authors MS. intended be educational resource support discussions between this evolving approach MS-specialized Recent progress (MS) development new treatments, therapies. Compared previous better at managing visible central nervous system, main cause worsening symptoms early people living Treatment means many achieve previously possible. One set criteria Achieving commonly criteria, that exhibit physical symptoms, magnetic resonance imaging scan. Researchers have studied it useful doctors measure person's progression response treatment. could inform important selection care explores available understand evaluations. discuss barriers being ways change capture broader range from patient. topics presented alongside meant assist conversations everyday practice.

Язык: Английский

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Magnetic Resonance Imaging Evidence Supporting the Efficacy of Cladribine Tablets in the Treatment of Relapsing-Remitting Multiple Sclerosis

CNS Drugs, Год журнала: 2024, Номер 38(4), С. 267 - 279

Опубликована: Март 15, 2024

Numerous therapies are currently available to modify the disease course of multiple sclerosis (MS). Magnetic resonance imaging (MRI) plays a pivotal role in assessing treatment response by providing insights into activity and clinical progression. Integrating MRI findings with laboratory data enables comprehensive assessment course. Among MS treatments, cladribine is emerging as promising option due its selective immune reconstitution therapy, notable impact on B cells lesser effect T cells. This work emphasizes MRI's contribution treatment, particularly focusing influence tablets outcomes, encompassing from real-world studies. The evidence highlights that cladribine, compared placebo, not only exhibits reduction inflammatory markers, such T1-Gd+, T2 combined unique active (CUA) lesions, but also mitigates brain volume loss, within grey matter. Importantly, reveals early action reducing CUA lesions first months regardless patient's initial conditions. mechanism action, sustained efficacy beyond year 2, onset collectively position component therapeutic paradigm for MS. Overall, MRI, along measures, has played substantial showcasing effectiveness addressing both neurodegenerative aspects

Язык: Английский

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Identifying Cladribine prescription pattern in MS: an Italian multicentre study

Therapeutic Advances in Neurological Disorders, Год журнала: 2025, Номер 18

Опубликована: Янв. 1, 2025

Background: Characterizing Cladribine tablets prescription pattern in daily clinical practice is crucial for optimizing multiple sclerosis (MS) treatment. Objectives: To describe efficacy, safety profile and new disease-modifying therapy (DMT) prescriptions following Design: Independent retrospective cohort study patients followed at six Italian MS centres. Methods: Patients diagnosed with relapsing (RMS) according to 2017 McDonald criteria, who initiated between January 2019 May 2023, were included. A generalized linear regression model was built the outcome DMT after course. Heatmaps generated based on weighted pivot tables visualize proportion of requiring post-Cladribine. Results: total 352 enrolled, 134 naïve any DMT, 218 switchers from other DMTs. The last an injectable first-line 48 (22%) patients, oral 141 (64.7%) SP1 inhibitor-Fingolimod 23 (10.6%) Natalizumab 6 (2.7%) patients. Overall, efficacious well tolerated, 12% required a median time 24 months. revealed that aged >40 years had 16% decrease likelihood receiving DMT. showed previously Fingolimod lower rate (72.2%) being free Cladribine. Conclusion: In our multicentric real-world study, generally effective during investigated follow-up period. Understanding key characteristics responding best can help tailor therapeutic strategies optimal outcomes.

Язык: Английский

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Additional Cladribine Tablets Treatment Courses in Multiple Sclerosis Patients. A Retrospective Observational Study in Latin American Countries

Multiple Sclerosis and Related Disorders, Год журнала: 2025, Номер 94, С. 106275 - 106275

Опубликована: Янв. 14, 2025

Язык: Английский

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Long-term efficacy and safety of alemtuzumab in participants with highly active MS: TOPAZ clinical trial and interim analysis of TREAT-MS real-world study

Therapeutic Advances in Neurological Disorders, Год журнала: 2025, Номер 18

Опубликована: Янв. 1, 2025

Background: Alemtuzumab is a disease-modifying therapy for highly active relapsing-remitting multiple sclerosis (RRMS). Sustained efficacy up to 9 years was observed in the phase IIIb/IV open-label TOPAZ clinical trial and assessed real-world retrospective prospective study, TREAT-MS. Objectives: To examine long-term safety of alemtuzumab participants with (MS) disease (HAD) by combining 13 data TREAT-MS interim data. Design: TOPAZ: Randomized completing core CARE-MS I II could receive additional (12 mg/day, 3 consecutive days; ⩾12 months apart) 11–13 after initiating treatment. TREAT-MS: Participants from German MS clinics were 4 last treatment phase. Methods: Efficacy outcomes (annualized relapse rate (ARR), change Expanded Disability Status Scale (EDSS), 6-month confirmed disability worsening/improvement, magnetic resonance imaging), adverse events (AEs) examined. Primary HAD definition (⩾2 relapses year prior baseline ⩾1 gadolinium-enhancing lesion at baseline), two alternative definitions assessed. Results: More (28%) (24%) met primary criteria than (~14%). Mean ARR alemtuzumab-treated significantly reduced (0.14 0.15, respectively, Years 3–13) (0.24, >2 years). Stable/improved EDSS scores achieved 74% I, 67% (both Year 11), 79% (Year 3.6), CDI about half 11 (CARE-MS II). Annual treatment-emergent AE incidences declined lower Conclusion: radiological study no new signals. Trial registration: ClinicalTrials.gov NCT00530348; II, NCT00548405; Extension Study, NCT00930553; TOPAZ, NCT02255656). Paul-Ehrlich-Institut (TREAT-MS, NIS 281).

Язык: Английский

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CSF levels of Chitinase3like1 correlate with early response to cladribine in multiple sclerosis

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Фев. 9, 2024

Background Cladribine has been introduced as a high-efficacy drug for treating relapsing-remitting multiple sclerosis (RRMS). Initial cohort studies showed early disease activity in the first year after initiation. Biomarkers that can predict are needed. Aim To estimate cerebrospinal fluid (CSF) markers of clinical and radiological responses initiation cladribine. Methods Forty-two RRMS patients (30F/12M) treated with cladribine were included longitudinal prospective study. All underwent CSF examination at treatment initiation, follow-up including Expanded Disability Status Scale (EDSS) assessment, 3T MRI scan 6,12 24 months, evaluation white matter (WM) cortical lesions (CLs). levels 67 inflammatory assessed immune-assay multiplex techniques. The ‘no evidence activity’ (NEDA-3) status was two years defined by no relapses, disability worsening measured EDSS activity, CLs. Results Three lost follow-up. At end follow-up, 19 (48%) remained free from activity. IFNgamma, Chitinase3like1, IL32, Osteopontin, IL12(p40), IL34, IL28A, sTNFR2, IL20 CCL2 best association When added multivariate regression model age, sex, baseline EDSS, Chitinase 3 like1 (p = 0.049) significantly increased those Finally, ROC analysis Chitinase3like1 to age previous WM lesion number, CLs, number Gad enhancing spinal cord provided an AUC 0.76 (95%CI 0.60-0.91). Conclusions might provide prognostic information predicting drug’s effect on chronic macrophage microglia activation deserves further evaluation.

Язык: Английский

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Administration and Monitoring Burden of High-Efficacy Disease-Modifying Therapies for Multiple Sclerosis: A Delphi Consensus of Clinical Experts from Saudi Arabia

Neurology and Therapy, Год журнала: 2025, Номер unknown

Опубликована: Янв. 4, 2025

The emergence of high-efficacy disease-modifying therapies (HE DMT) for multiple sclerosis (MS) may pose challenges to the administration and monitoring burden therapies. This article presents results Delphi consensus method generate insights from experts on HE DMT in Saudi Arabia with a special focus cladribine. Between January March 2023, two-round modified was used establish regarding DMTs MS. Through questionnaire, advisors evaluated 17 properties six individual basis their clinical experience. Advisors were required rank each property scale 1–5, 1 being lowest 5 highest burden. Experts ranked cladribine as having burden, followed by ofatumumab ocrelizumab. Natalizumab fingolimod fourth, alemtuzumab had During first round, agreed scores properties, except hospital visit time facility use during ofatumumab, route fingolimod, specific side effects frequency lab tests at follow-up, washout period natalizumab. second there agreement all properties. In absence alternative scientific data, recommendations provide useful into MS Arabia.

Язык: Английский

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Treatment with Cladribine Tablets Beyond Year 4: A Position Statement by Southeast European Multiple Sclerosis Centers

Neurology and Therapy, Год журнала: 2022, Номер 12(1), С. 25 - 37

Опубликована: Ноя. 17, 2022

Based on the results of pivotal CLARITY study, cladribine tablets were approved for use in European Union 2017 as a high-efficacy therapy highly active relapsing-remitting multiple sclerosis (MS). Cladribine are used an induction therapy: half total dose is given year 1 and other 2. In Extension trials, repeating routinely years 3 4, was not associated with significantly improved disease control. However, there very limited evidence how to manage people MS (pwMS) beyond which increasingly important because more patients now ≥ 4 after treatment. Overall, postapproval data show that treatment two cycles effectively controls activity long term. general agreement some pwMS suboptimal response could benefit from retreatment. This study reviews practical aspects using tablets, summarizes clinical trials real-world studies safety efficacy cladribine, proposes algorithm developed by expert consensus previously treated cladribine. brief, we propose additional courses should be considered minimal (no relapses, 1-2 new lesions) or moderate (1 relapse, 3-4 activity, while significant (> > progression warrant switch another (HET). More needed improve guidelines who received

Язык: Английский

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Expert Narrative Review of the Safety of Cladribine Tablets for the Management of Relapsing Multiple Sclerosis

Neurology and Therapy, Год журнала: 2023, Номер 12(5), С. 1457 - 1476

Опубликована: Июнь 29, 2023

Cladribine tablets (CladT) is a highly active oral disease-modifying therapy (DMT) for the management of relapsing multiple sclerosis (RMS). CladT acts as an immune reconstitution therapy, in that two short courses treatment 1 year apart have been shown to suppress disease activity prolonged period most patients, without need continued DMT. Each course induces profound reduction B lymphocytes recovers over months, and serious lymphopenia (Grade 3–4) uncommon. Smaller reductions levels T occur slightly later: on average, these remain within normal range repopulate progressively. A larger effect occurs CD8 vs. CD4 cells. Reactivation latent or opportunistic infections (e.g. varicella zoster, tuberculosis) mostly associated with very low lymphocyte counts (< 200/mm3). Screening managing pre-existing infections, vaccinating non-exposed patients delaying 2nd allow recover > 800/mm3 (if necessary) are important avoiding higher-grade lymphopenia. There was no demonstrable apparent efficacy vaccinations, including against Covid-19. Adverse events consistent drug-induced liver injury (DILI) represent rare but potentially complication spontaneous adverse event reporting; should be screened dysfunction before starting treatment. Ongoing hepatic monitoring not required, must withdrawn if signs symptoms DILI develop. numerical imbalance malignancies when comparing cladribine placebo clinical programme, particularly short-term data, recent evidence shows risk malignancy similar background rate general population other DMTs. Overall, well tolerated favorable safety profile appropriate RMS.

Язык: Английский

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