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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Real-world experience of cladribine treatment in relapsing-remitting multiple sclerosis: A Danish nationwide study

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

Опубликована: Дек. 28, 2022

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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Long-term management of multiple sclerosis patients treated with cladribine tablets beyond year 4

Expert Opinion on Pharmacotherapy, Год журнала: 2022, Номер 23(13), С. 1503 - 1510

Опубликована: Авг. 5, 2022

Oral cladribine is a highly effective pulsed selective immune reconstitution therapy licensed for relapsing multiple sclerosis (RMS) since 2017. A full treatment course comprises two cycles given 1 year apart, followed by treatment-free years. The management of cladribine-treated patients beyond 4 needs to be addressed as have now passed the initial years European Medical Agency approval.A panel neurologists and neuroradiologist experienced in MS treatment/monitoring evaluated clinical trial data real-world evidence proposed recommendations 4.Continuous monitoring disease activity during period important. Subsequent depends on presence or absence inflammatory activity, determined consistent guidelines via practice-driven neurological decision criteria. Persisting newly occurring an indication further treatment, i.e. either re-initiation switching another disease-modifying therapy. retreat switch should based radiological evaluation considering course, history, safety aspects. In retreatment can offered, extended under structured monitoring.

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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Comparative effectiveness of cladribine tablets versus fingolimod in the treatment of highly active multiple sclerosis: A real-world study

Multiple Sclerosis and Related Disorders, Год журнала: 2023, Номер 76, С. 104791 - 104791

Опубликована: Июнь 3, 2023

Cladribine tablets and fingolimod have similar marketing authorisations in Europe for the treatment of patients with highly active relapsing multiple sclerosis (HA-RMS). In absence direct head-to-head studies, real-world data are important to assess comparative effectiveness these oral disease-modifying therapies (DMTs). The primary objective present study was compare relapse rates between who received either cladribine or fingolimod.This multicentre retrospective conducted United Kingdom Germany assessed non-inferiority versus HA-RMS over a 12-month period. Eligible initiated at least 12 months prior screening date were sampled consecutively until target sample size reached. Patients censored discontinuation treatment, commencement another DMT, death, loss follow-up, post-baseline, whichever happened earliest. analytic timeframe physician-confirmed outcomes period (nine follow-up after an initial weeks treatment). Propensity score analysis applied based on inverse probability weighting approach.The cohort consisted 1,095 patients: 610 (55.7%) receiving 485 (44.3%) fingolimod. Fewer discontinued and/or switched DMT compared (0.2% 3.5%, respectively). endpoint, adjusted annualised rate (ARR), 0.10 (95% confidence interval [CI]: 0.07-0.14) 0.14 CI: 0.10-0.20) ARR ratio 0.68 0.42-1.11). Given entire 95% CI less than margin 1.2, non-inferior fingolimod.In this study, demonstrated comparable one year following initiation. full dosage is completed two years so results may be conservative.

Язык: Английский

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Effect of Prior Treatment With Fingolimod on Early and Late Response to Rituximab/Ocrelizumab in Patients With Multiple Sclerosis

Neurology Neuroimmunology & Neuroinflammation, Год журнала: 2024, Номер 11(3)

Опубликована: Апрель 16, 2024

Real-life studies noted that the risk of disease activity in multiple sclerosis (MS) after switching to rituximab (RTX) or ocrelizumab (OCR) may be unequal depending on prior disease-modifying therapy (DMT), with a higher associated fingolimod (FING). We performed retrospective analysis structured prospective data collection including all consecutive patients relapsing MS who were prescribed RTX/OCR center Marseille. Cox proportional hazards models applied clinical and MRI outcomes. included 321 median (interquartile range [IQR]) follow-up 3.5 years (1.5-5) initiation. At first infusion, mean (SD) age was 37 (10) years, (IQR) duration 8 (3-15): 68 did not receive treatment before 108 switched from FING, 47 low efficacy therapy, 98 natalizumab. For statistical analysis, group "FING" divided into "short-FING" "long-FING" groups according value group's washout period (27 days). On for only group, relapse within 6 months increased as compared without previous DMT (hazard ratio [HR]: 8.78; 95% CI 1.72-44.86; p < 0.01). Previous FING had no effect B-cell levels at months. Beyond RTX/OCR, <40 (HR: 3.93; 1.30-11.89; = 0.01), male sex new T2 lesions 2.26; 1.08-4.74; 0.03), EDSS ≥2 disability accumulation 3.01; 1.34-6.74; effectiveness beyond reactivation other when exceeded 26 days. Neither nor reduced treatment.

Язык: Английский

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Safety and effectiveness of cladribine tablets for multiple sclerosis: Results from a single-center real-world cohort

Multiple Sclerosis and Related Disorders, Год журнала: 2023, Номер 75, С. 104735 - 104735

Опубликована: Апрель 26, 2023

Язык: Английский

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