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 Ongoing hepatic monitoring not required, must withdrawn if signs symptoms DILI develop.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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Safety and Effectiveness of Cladribine in Multiple Sclerosis: Real-World Clinical Experience From 5 Tertiary Hospitals in Portugal

Clinical Neuropharmacology, Год журнала: 2023, Номер unknown

Опубликована: Апрель 10, 2023

Objectives Cladribine is a selective and oral immunological reconstitution treatment, approved in Europe for very active multiple sclerosis (MS) with relapses. Aims were to assess the safety effectiveness of cladribine real-world setting, during treatment follow-up. Methods This was multicentric, longitudinal, observational study retrospective prospective data collection clinical, laboratory, imaging data. interim analysis reports from July 1, 2018 (study onset), March 31, 2021. Results A total 182 patients enrolled: 68.7% female; mean age at onset 30.1 ± 10.0 years, first cycle 41.1 12.1; 88.5% diagnosed relapse-remitting MS 11.5% secondary progressive MS. Mean disease duration start 8.9 7.7 years. Most (86.1%) not naive, median number previous disease-modifying therapies 2 (interquartile range, 1–3). At 12 months, we observed no significant Expanded Disability Status Scale score worsening ( P = 0.843, Mann-Whitney U test) significantly lower annualized relapse rate (0.9 baseline 0.2; 78% reduction). discontinuation registered 8% patients, mainly (69.2%) due activity persistence. frequent adverse reactions lymphocytopenia (55%), infections (25.2%), fatigue (10.7%). Serious effects reported 3.3%. No patient has discontinued because effects. Conclusion Our confirms clinical efficacy profile treating long-term setting. contribute body knowledge management improvement related outcomes.

Язык: Английский

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Results of treatment with alemtuzumab in a Spanish cohort of patients with multiple sclerosis in the real world: The RealMS study

Frontiers in Neurology, Год журнала: 2023, Номер 14

Опубликована: Март 14, 2023

Alemtuzumab (ALZ) is a humanized monoclonal antibody approved for the treatment of patients with highly active relapsing-remitting multiple sclerosis (RRMS) administered in two annual courses. The objective this study was to describe effectiveness and safety data ALZ report health resource utilization receiving treatment.In retrospective, non-interventional study, information retrieved from patients' medical charts at one center Spain. Included were ≥18 years old, initiated between 1 March 2015 31 2019, according routine clinical practice local labeling.Of 123 patients, 78% women. mean (standard deviation, SD) age diagnosis 40.3 (9.1) years, time since 13.8 (7.3) years. Patients previously treated median (interquartile range; IQR) number (2.0-3.0) disease-modifying treatments (DMTs). (SD) 29.7 (13.8) months. reduced annualized relapse rate (ARR) (1.5 before vs. 0.05 after; p < 0.001) improved EDSS (4.63 4.00 0.001). Most (90.2%) relapse-free while ALZ. gadolinium-enhancing [Gd+] T1 lesions (1.7 0.1 0.001), T2 hyperintense maintained (35.7 35.4 = 0.392). A total 27 (21.9%) reported 29 autoimmune diseases: hyperthyroidism (12), hypothyroidism (11), idiopathic thrombocytopenic purpura (ITP) (3), alopecia areata (1), chronic urticaria vitiligo (1). resources (outpatient visits, emergency room hospital admissions, tests performed hospital) used progressively decreased year 4, except slight increase 2 outpatient visits.The ReaLMS provides real-world evidence that can promote magnetic resonance imaging disease remission, as well disability improvement MS, despite several prior DMT failures. profile consistent available trials other studies. Healthcare use throughout period.

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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Alemtuzumab treatment in real clinical practice: Experience in a multicenter cohort.

Multiple Sclerosis and Related Disorders, Год журнала: 2023, Номер 75, С. 104762 - 104762

Опубликована: Май 13, 2023

Язык: Английский

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The Place of Immune Reconstitution Therapy in the Management of Relapsing Multiple Sclerosis in France: An Expert Consensus

Neurology and Therapy, Год журнала: 2022, Номер 12(2), С. 351 - 369

Опубликована: Дек. 24, 2022

The treatment strategy in relapsing multiple sclerosis (RMS) is a complex decision requiring individualization of sequences to maximize clinical outcomes. Current local and international guidelines do not provide specific recommendation on the use immune reconstitution therapy (IRT) as alternative continuous immunosuppression management RMS. objective program was consensus-based expert opinion optimal IRT A Delphi method performed from May 2022 July 2022. Nineteen assertions were developed by scientific committee sent 14 French experts MS alongside published literature. Two consecutive reproducible anonymous votes conducted. Consensus recommendations achieved when more than 75% respondents agreed or disagreed with assertions. After second round, consensus amongst 16 out 19 propositions: 13 had 100% consensus, 3 above without consensus. Expert-agreed provided topics related benefit early immunological perspectives, profiles patients who may most (e.g. family planning, patient preference lifestyle requirements). These consensuses up-to-date relevant guidance practice. current reflects status knowledge should be updated timely manner further data become available.

Язык: Английский

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Real-World Effectiveness of Cladribine for Patients with Multiple Sclerosis: A Sicilian Multicentric Experience (Rewind Study)

Current Neuropharmacology, Год журнала: 2023, Номер 22(7), С. 1271 - 1283

Опубликована: Март 22, 2023

Background: Cladribine tablets are a highly effective option for the treatment of relapsingremitting multiple sclerosis (RRMS). Objective: The study aims to evaluate effectiveness cladribine in real-world setting. Methods: This prospective consecutively screened all RRMS patients from seven different MS centers Sicily (Italy) who completed 2-year course period between 11th March 2019 and 31st October 2021. Data about Expanded Disability Status Scale (EDSS), relapses, previous treatments, adverse events (AEs) magnetic resonance imaging (MRI) were collected. Patients previously treated with other DMTs further stratified into moderately active (MAT) (HAT) patients. Results: A total 217 (70% women, mean age 38.4 ± 11.3 years) enrolled. Fifty (23.0%) naïve 167 (77%) switched disease modifying therapies. After second year treatment, 80% EDSS progression free, 88% remained relapse-free at T24, 48% MRI activity-free. Kaplan Meier analyses showed significant differences MT HAT terms time first clinical relapse (HR: 2.43, IC 1.02- 5.76; p = 0.04), new T1-gadolinium enhancing lesion 3.43, 1.35-8.70; 0.009) worsening 2.42, 1.15-5.09; 0.02). Conclusion: confirmed that is an MS, particularly those have MATs.

Язык: Английский

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Cladribine tablets in people with relapsing multiple sclerosis: A real-world multicentric study from southeast European MS centers

Journal of Neuroimmunology, Год журнала: 2023, Номер 382, С. 578164 - 578164

Опубликована: Июль 27, 2023

Язык: Английский

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Risk of secondary autoimmune diseases with alemtuzumab treatment for multiple sclerosis: a systematic review and meta-analysis

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Апрель 16, 2024

Background and purpose The objective of this study is to evaluate the risk secondary autoimmune diseases in multiple sclerosis (MS) patients treated with alemtuzumab (ALZ) through a meta-analysis. Methods PubMed, Web Science, OVID, EMBASE, Cochrane central register controlled trials were searched. Information data screened extracted by 2 researchers. obtained analyzed using R software meta package. Quality assessment was conducted Newcastle-Ottawa Scale (NOS). causes heterogeneity subgroup analysis sensitivity analysis. Publication bias evaluated funnel plots Egger’s test. Results search retrieved total 3530 papers from databases. After screening, 37 studies included results indicate that pooled incidence rate overall events (SAEs) 0.2824 [0.2348, 0.3300] (I²=94%, p&lt;0.01). thyroid (ATE) 0.2257 [0.1810, 0.2703] Among them, serious (SATE) 0.0541 [0.0396, 0.0687] (I²=0%, p=0.44). rates different as follows: Graves’ disease (GD), 0.2266 [0.1632, 0.2900] (I²=83%, p&lt;0.01); Hashimoto thyroiditis (HT), 0.0844 [0.0000, 0.2262] (I²=81%, p=0.02); hypothyroidism (HTwH), 0.0499 [0.0058, 0.0940] (I²=37%, p=0.21); fluctuating dysfunction (FTD), 0.0219 [0.0015, 0.0424] p=0.40); transient (TT), 0.0178 [0.0062, 0.0295] p=0.94). hematological 0.0431 [0.0274, 0.0621] (I²=70%, high low lymphopenia, 0.0367 0.0776] Idiopathic thrombocytopenic purpura (ITP), 0.0258 [0.0199, 0.0323] (I²=25%, p=0.15); Hemolytic anemia (HA), 0.0177 [0.0081, 0.0391] (I²=29%, p=0.23); pancytopenia, 0.0136 0.0314] p=0.67); Neutropenia, 0.0081 0.0183] p=0.42). excluding diseases, combined other related SAEs 0.0061 [0.0014, 0.0109] (I²=50%, p=0.02). each ranked highest lowest as: skin psoriasis (SP), 0.0430 0.0929] p=0.57); alopecia areata (AA), 0.0159 [0.0024, 0.0372] (I²=19%, p=0.29); vitiligo, 0.0134 [0.0044, 0.0223] p=0.81); inflammatory atrichia (IA), 0.0103 0.0232] p=0.43); chronic urticaria (CU), 0.0107 0.0233] p=0.60); nephropathy, 0.0051 0.0263] (I²=62%, Conclusion occurrence MS ALZ noteworthy, particularly form events. Clinicians should monitor condition promptly for early management avoid delayed diagnosis treatment. Systematic review registration inplasy.com/inplasy-2024-4-0048/ , identifier INPLASY202440048.

Язык: Английский

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Alemtuzumab treatment for multiple sclerosis in Austria: An observational long‐term outcome study

Annals of Clinical and Translational Neurology, Год журнала: 2024, Номер 11(6), С. 1442 - 1455

Опубликована: Май 7, 2024

Abstract Background/Objective Observational real‐world study to analyze the clinical effects of alemtuzumab (ALEM) and subsequent disease‐modifying therapy (DMT) usage in multiple sclerosis (MS). Methods Data retrieved from Austrian MS treatment registry (AMSTR) included baseline (BL) characteristics (at ALEM start), annualized relapse rate (ARR), 6‐month confirmed progression independent activity (PIRA; ≥ 0.5‐point Expanded Disability Status Scale (EDSS) score increase), disability improvement (CDI; EDSS decrease), safety outcomes until initiation a DMT. The was re‐baselined at 30 days start (BL EDSS). Results Eighty‐seven ALEM‐treated patients (median age: 32 years, 72% female, 14% treatment‐naïve) were followed for median 55 (interquartile range 31–68) months. We found significant reductions ARR 1.16 before 0.15 throughout Years 1–9 ( p < 0.001). Subsequent DMTs initiated 19 (22%, 74% anti‐CD20 monoclonal antibodies). At Year 5 n = 53), more achieved CDI (58%, 95% confidence interval (CI) 45%–71%) than had experienced PIRA (14%, CI 7.5%–24%), 58% remained relapse‐free. Shorter duration 0.001, hazard ratio (HR) 0.86 (CI 0.80–0.93)) no previous high‐efficacy HR 5.16 2.66–10.0)) best predictors CDI, while associated with higher number 0.04, 3.06, 1.05–8.89). new signals. Interpretation long‐lasting beneficial on improvement, especially when early course disease. Only subset received DMTs.

Язык: Английский

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