Effect of cladribine tablets on lymphocyte reduction and repopulation dynamics in patients with relapsing multiple sclerosis.

  title={Effect of cladribine tablets on lymphocyte reduction and repopulation dynamics in patients with relapsing multiple sclerosis.},
  author={Giancarlo Comi and Stuart D. Cook and Gavin Giovannoni and Peter Rieckmann and Per Soelberg S{\o}rensen and Patrick Vermersch and Andrew R. Galazka and Axel Nolting and Christine Hicking and Fernando Dangond},
  journal={Multiple sclerosis and related disorders},

Figures and Tables from this paper

Cladribine Tablets for Relapsing–Remitting Multiple Sclerosis: A Clinician’s Review

Cladribine tablets represent a selective, high-efficacy, oral form of IRT for patients with MS that targets lymphocytes and spares innate immune cells and is associated with a lower monitoring burden than many other DMTs, while short dosing periods can help to improve adherence.

Integrated Lymphopenia Analysis in Younger and Older Patients With Multiple Sclerosis Treated With Cladribine Tablets

CladT3.5 had a similar effect on ALC and lymphocyte subsets in both younger and older patient groups and the rate of certain infections was numerically higher in older versus younger patients who experienced Gr≥3L.

Safety of cladribine tablets in the treatment of patients with multiple sclerosis: An integrated analysis.

Immunological consequences of cladribine treatment in multiple sclerosis: A real-world study.

Real-world evidence for cladribine tablets in multiple sclerosis: further insights into efficacy and safety

It is concluded that the current real-world evidence for CLAD tablets as immune reconstitution therapy for treatment of MS is based on a small number of studies and a population distinct from the cohorts randomized in the pivotal phase III trials.

The Development of Cladribine Tablets for the Treatment of Multiple Sclerosis: A Comprehensive Review

A review of all safety data, including lymphopenia, infections, and malignancies, is provided based on data from all trials in patients with MS, including the initial parenteral formulation studies.

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

It is proposed that additional courses of cladribine tablets should be considered in patients with minimal or moderate disease activity, while significant disease activity or progression should warrant a switch to another high-efficacy treatment (HET).



Cladribine to Treat Relapsing Forms of Multiple Sclerosis

Data from the oral cladribine extension trial and safety register, and reanalysis of the pivotal phase III trial has indicated that oralcladribine is unlikely to be associated with an increased short- to intermediate-term risk of malignancy.

Effects of Postponing Treatment in the Second Year of Cladribine Administration: Clinical Trial Simulation Analysis of Absolute Lymphocyte Counts and Relapse Rate in Patients with Relapsing-Remitting Multiple Sclerosis

Results support treatment guidelines to decrease the risk of severe lymphopenia following treatment with Cladribine Tablets, while preserving efficacy.

A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis.

Treatment with cladribine tablets significantly reduced relapse rates, the risk of disability progression, and MRI measures of disease activity at 96 weeks, and the benefits need to be weighed against the risks.

Cladribine tablets for the treatment of relapsing–remitting multiple sclerosis

This article provides an overview of the chemistry, mechanism of action and pharmacological properties of cladribine tablets therapy, and highlights the rationale for its development as an oral treatment for MS.

Long term lymphocyte reconstitution after alemtuzumab treatment of multiple sclerosis

Lymphocyte counts recovered to LLN after a single course of alemtuzumab in approximately 8 months (B cells) and 3 years (T cell subsets), but usually did not recover to baseline values, however, this long lasting lymphopenia in patients with a previously normal immune system was not associated with an increased risk of serious opportunistic infection.

Both cladribine and alemtuzumab may effect MS via B-cell depletion

Cladribine induced only modest depletion of T cells, which may not be consistent with a marked influence on MS, based on previous CD4+ T-cell depletion studies, and the success seen with monoclonal CD20+ depletion, suggests that B-cell suppression could be the major direct mechanism of action.

Long-term effects of cladribine tablets on MRI activity outcomes in patients with relapsing–remitting multiple sclerosis: the CLARITY Extension study

A 2-year treatment with CT 3.5 mg/kg has a durable effect on MRI outcomes in the majority of patients, an effect that was sustained in patients who were not retreated in the subsequent 2 years after initial treatment.

Durable efficacy of cladribine tablets in patients with multiple sclerosis: analysis of relapse rates and relapse-free patients in the CLARITY and CLARITY Extension studies (P6.353)

Comparing CLarITY with CLARITY EXT demonstrates that CT produced durable clinical benefits: patients who received CT in CLarity and PBO in CLARity EXT maintained low relapse rates throughout.

Interpreting Lymphocyte Reconstitution Data From the Pivotal Phase 3 Trials of Alemtuzumab

Although blockade of memory T and B cells may limit MS, rapid CD19+ B-cell subset repopulation in the absence of effective T-cell regulation has implications for the safety and efficacy of alemtuzumab.

Safety and efficacy of cladribine tablets in patients with relapsing–remitting multiple sclerosis: Results from the randomized extension trial of the CLARITY study

Cladribine tablets treatment for 2’ years followed by 2 years’ placebo treatment produced durable clinical benefits similar to 4’years of cladribine treatment with a low risk of severe lymphopenia or clinical worsening.