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Safety and tolerability of cladribine tablets in multiple sclerosis: the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study.
Cook, S; Vermersch, P; Comi, G; Giovannoni, G; Rammohan, K; Rieckmann, P; Sørensen, P Soelberg; Hamlett, A; Miret, M; Weiner, J; Viglietta, V; Musch, B; Greenberg, S J.
Afiliación
  • Cook S; University of Medicine and Dentistry, New Jersey Medical School, Newark, NJ 07101, USA. cooksd@umdnj.edu
Mult Scler ; 17(5): 578-93, 2011 May.
Article en En | MEDLINE | ID: mdl-21228029
BACKGROUND: Cladribine is a synthetic deoxyadenosine analogue in development as an oral multiple sclerosis (MS) therapy. OBJECTIVE: To report in detail the safety findings from the 96-week, phase III, double-blind CLARITY study, which evaluated treatment with cladribine tablets in relapsing-remitting MS. METHODS: A total of 1,326 patients were randomized 1:1:1 to two short-course regimens of cladribine tablets (3.5 or 5.25 mg/kg cumulative dose over 96 weeks) or placebo. Safety assessments included monitoring for adverse events (AEs), routine physical and neurologic examinations and frequent laboratory parameter assessments. RESULTS: Of the randomized patients, 88.6% completed treatment with cladribine tablets versus 86.3% with placebo. Lymphopenia was the most commonly reported AE in patients treated with cladribine tablets and was anticipated based on the mechanism of action. The incidence of infections was 48.3% with cladribine tablets and 42.5% with placebo, with 99.1% and 99.0% rated mild-to-moderate by investigators. Herpes zoster infections developed in 20 (2.3%) cladribine-treated patients; all cases were dermatomal. There were no herpes zoster infections in the placebo group. Nine (1.0%) patients experienced events related to uterine leiomyomas in the cladribine tablets groups versus one (0.2%) with placebo. Three isolated cases of malignancy were reported in cladribine-treated patients during the study; a fourth was reported during post-study surveillance. A pre-malignant cervical carcinoma in situ was also reported. The incidence of malignancies during the study did not exceed the expected rate in a population standardized for country, gender and age. CONCLUSION: The safety and tolerability profile observed in the CLARITY study together with the reported efficacy support the potential for cladribine tablets as an MS therapy.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cladribina / Esclerosis Múltiple Recurrente-Remitente / Inmunosupresores Tipo de estudio: Clinical_trials / Diagnostic_studies / Etiology_studies / Risk_factors_studies Límite: Adult / Humans / Male / Middle aged País/Región como asunto: America do norte / Europa Idioma: En Revista: Mult Scler Asunto de la revista: NEUROLOGIA Año: 2011 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cladribina / Esclerosis Múltiple Recurrente-Remitente / Inmunosupresores Tipo de estudio: Clinical_trials / Diagnostic_studies / Etiology_studies / Risk_factors_studies Límite: Adult / Humans / Male / Middle aged País/Región como asunto: America do norte / Europa Idioma: En Revista: Mult Scler Asunto de la revista: NEUROLOGIA Año: 2011 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido