Expert opinion on the long-term use of cladribine tablets for multiple sclerosis: Systematic literature review of real-world evidence

Oreja‐Guevara, Celia; Brownlee, Wallace; Celius, Elisabeth Gulowsen; Centonze, Diego; Giovannoni, Gavin; Hodgkinson, Suzanne; Kleinschnitz, Christoph; Havrdová, Eva; Magyari, Melinda; Selchen, Daniel; Vermersch, Patrick; Wiendl, Heinz; Wijmeersch, Bart Van; Salloukh, Hashem; Yamout, Bassem

doi:10.1016/j.msard.2022.104459

Cited by 22 publications

(31 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The long-term effects of treatment with cladribine tablets and the management of patients after year 4 are currently topics of significant discussion among clinicians, as evidenced by numerous expert opinion reports [ 81 – 85 ]. These reports emphasize the importance of utilizing all available tools and techniques, including clinical, radiological, and biological markers, to identify and manage patients who may benefit from additional courses of cladribine tablets.…”

Section: Efficacy Of Cladribine Tablets In the Real-world Settingmentioning

confidence: 99%

“…These reports emphasize the importance of utilizing all available tools and techniques, including clinical, radiological, and biological markers, to identify and manage patients who may benefit from additional courses of cladribine tablets. Specifically, alongside evaluation of clinical and serum markers, MRI is highlighted as a key tool in guiding therapeutic decisions and identifying patients suitable for further treatment with cladribine tablets [ 81 , 82 , 84 , 85 ].…”

Section: Efficacy Of Cladribine Tablets In the Real-world Settingmentioning

confidence: 99%

See 1 more Smart Citation

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

Cortese,

Testa,

Assogna

et al. 2024

CNS Drugs

View full text Add to dashboard Cite

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

show abstract

Section: Efficacy Of Cladribine Tablets In the Real-world Settingmentioning

confidence: 99%

Section: Efficacy Of Cladribine Tablets In the Real-world Settingmentioning

confidence: 99%

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

Cortese,

Testa,

Assogna

et al. 2024

CNS Drugs

View full text Add to dashboard Cite

show abstract

“…Į sisteminę literatūros apžvalgą įtrauktose publikacijose (klinikinių tyrimų ir realaus gyvenimo duomenų) pacientų dalis, kuriai atkrytis išsivystė pirmaisiais, antraisiais-ketvirtaisiais ir penktaisiais metais nuo kladribino tablečių paskyrimo, atitinkamai buvo 4,8-21,9 %, 12-18,7 % ir 30-50 % [24].…”

Section: įVadasunclassified

Treatment of Multiple Sclerosis with Cladribine Tablets: Literature Review and the Guidance of the Lithuanian Association of Neurologists

Kizlaitienė,

Mickevičienė,

Malcienė

et al. 2024

View full text Add to dashboard Cite

Cladribine is a disease-modifying drug used for the treatment of the highly active relapsing-remitting form of multiple sclerosis. Cladribine is a purine nucleoside analogue which selectively targets lymphocyte subpopulations involved in the pathogenesis of multiple sclerosis, and therefore it is classified as an immune reconstitution therapy drug. Two short courses of cladribine tablets given over two years significantly reduce the multiple sclerosis relapse rate and disability progression. For most patients, the effect persists in the third and the fourth year. This makes cladribine convenient for patients with multiple comorbidities, difficulties in adhering to their prescribed treatment regimen, those planning a pregnancy, or those for whom long-term immunosuppression is undesirable. Cladribine tablets are denoted by good safety characteristics, with the most prominent adverse effect being lymphopenia, which does not lead to an increased risk of infections other than Herpes zoster.However, in clinical practice, there are a number of issues related both to the initial administration of cladribine tablets and the strategy of treatment in different clinical situations during the first-to-fourth years of treatment, and particularly after the fourth year. Although there are no contraindications for additional courses of cladribine tablets, the product information does not provide detailed guidance on their continued use. During more than five years after the approval of the medicinal product, the new clinical trial data and the Real-World Evidence (RWE) on the efficacy and safety of cladribine tablets have become available, based on which, several national and international expert panels, as well as the Lithuanian Association of Neurologists, have issued guidance on the use of cladribine tablets reviewed in this article. Upon reactivation of the disease, additional courses of cladribine tablets or other disease-modifying therapies may be prescribed, depending on various factors related to the severity of the relapse, patient characteristics, and previously used medications. If the patient’s condition remains stable after the fourth year, extension of the treatment-free period with the structured monitoring approach could be appropriate.

show abstract

“…41 A systematic review of real-world evidence on the use of cladribine tablets for MS revealed that more real-world studies with longer follow-up periods are needed. 42 Meanwhile, the ongoing 'Cladribine, a Multicenter, Long-term Efficacy and Biomarker Australian Study' (CLOBAS) is collecting prospective realworld data on the safety and efficacy (NEDA-3) of cladribine tablets, including the option of early retreatment in year 3. 43 Monitoring will include MRI, as well as cognitive performance and biomarkers, including lymphocyte subsets, serum neurofilament light chain (sNfL), DNA methylation, and RNA analysis.…”

Section: Aimmentioning

confidence: 99%

“… 41 A systematic review of real-world evidence on the use of cladribine tablets for MS revealed that more real-world studies with longer follow-up periods are needed. 42 …”

Section: Introductionmentioning

confidence: 99%

Multiple sclerosis patients treated with cladribine tablets: expert opinion on practical management after year 4

Centonze

Amato

Morra

et al. 2023

Ther Adv Neurol Disord

Self Cite

View full text Add to dashboard Cite

Multiple sclerosis (MS) is a chronic, progressive neurological disease involving neuroinflammation, neurodegeneration, and demyelination. Cladribine tablets are approved for immune reconstitution therapy in patients with highly active relapsing–remitting MS based on favorable efficacy and tolerability results from the CLARITY study that have been confirmed in long-term extension studies. The approved 4-year dosing regimen foresees a cumulative dose of 3.5 mg/kg administered in two cycles administered 1 year apart, followed by 2 years of observation. Evidence on managing patients beyond year 4 is scarce; therefore, a group of 10 neurologists has assessed the available evidence and formulated an expert opinion on management of the growing population of patients now completing the approved 4-year regimen. We propose five patient categories based on response to treatment during the first 4-year regimen, and corresponding management pathways that envision close monitoring with clinical visits, magnetic resonance imaging (MRI) and/or biomarkers. At the first sign of clinical or radiological disease activity, patients should receive a highly effective disease-modifying therapy, comprising either a full cladribine regimen as described in regulatory documents (cumulative dose 7.0 mg/kg) or a comparably effective treatment. Re-treatment decisions should be based on the intensity and timing of onset of disease activity, clinical and radiological assessments, as well as patient eligibility for treatment and treatment preference.

show abstract

Expert opinion on the long-term use of cladribine tablets for multiple sclerosis: Systematic literature review of real-world evidence

Cited by 22 publications

References 46 publications

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

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

Treatment of Multiple Sclerosis with Cladribine Tablets: Literature Review and the Guidance of the Lithuanian Association of Neurologists

Multiple sclerosis patients treated with cladribine tablets: expert opinion on practical management after year 4

Contact Info

Product

Resources

About