Effect of cladribine tablets on lymphocyte reduction and repopulation dynamics in patients with relapsing multiple sclerosis.
Mult Scler Relat Disord
; 29: 168-174, 2019 Apr.
Article
em En
| MEDLINE
| ID: mdl-30885375
ABSTRACT
BACKGROUND:
Immune reconstitution therapies (IRT) for patients with multiple sclerosis are used for short, intermittent treatment periods to induce immune resetting and allow subsequent treatment-free periods. Cladribine tablets are postulated to be an IRT that causes selective and transient reductions in CD19+ B cells and T cells, followed by reconstitution of adaptive immune function.OBJECTIVE:
To characterize long-term lymphocyte count changes in pooled data from the 2-year CLARITY and subsequent 2-year CLARITY Extension studies, and the PREMIERE registry (Long-term CLARITY cohort).METHODS:
Data from patients randomized to placebo (nâ¯=â¯435) or cladribine tablets 10â¯mg (MAVENCLAD®; 3.5â¯mg/kg cumulative dose over 2 years, referred to as cladribine tablets 3.5â¯mg/kg; nâ¯=â¯685) in CLARITY or CLARITY Extension, including time spent in the PREMIERE registry were pooled to provide long-term follow-up data. The study investigated absolute lymphocyte counts (ALC) up to 312 weeks and B and T cell subsets up to 240 weeks after the first dose, in patients receiving placebo or cladribine tablets 3.5â¯mg/kg administered as two short (4 or 5 days) weekly treatments at the start of months 1 and 2 in each treatment year, followed by no further active treatment.RESULTS:
Treatment with cladribine tablets 3.5â¯mg/kg resulted in selective reductions in B and T lymphocytes. Lymphocyte recovery began soon after treatment in each of years 1 and 2. Median ALC recovered to the normal range and CD19+ B cells recovered to threshold values by week 84, approximately 30 weeks after the last dose of cladribine tablets in year 2. Median CD4+ T cell counts recovered to threshold values by week 96 (approximately 43 weeks after the last dose of cladribine tablets in year 2). Median CD8+ cell counts never dropped below the threshold value.CONCLUSION:
These results show the dynamics of lymphocyte count changes following treatment with cladribine tablets 3.5â¯mg/kg. The immune cell repopulation results provide further evidence that cladribine tablets may represent a form of IRT.Palavras-chave
Texto completo:
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Eixos temáticos:
Pesquisa_clinica
Base de dados:
MEDLINE
Assunto principal:
Linfócitos
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Sistema de Registros
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Avaliação de Resultados em Cuidados de Saúde
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Cladribina
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Esclerose Múltipla Recidivante-Remitente
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Imunossupressores
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Linfopenia
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Incidence_studies
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Observational_studies
/
Risk_factors_studies
Limite:
Adolescent
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Adult
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Aged
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article