Safety and tolerability of cladribine tablets in multiple sclerosis: The CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study

S. Cook, P. Vermersch, G. Comi, G. Giovannoni, Kottil W Rammohan, P. Rieckmann, P. Soelberg Sørensen, A. Hamlett, M. Miret, J. Weiner, V. Viglietta, B. Musch, S. J. Greenberg

Research output: Contribution to journalArticle

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Abstract

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%) cladribinetreated 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.

Original languageEnglish
Pages (from-to)578-593
Number of pages16
JournalMultiple Sclerosis
Volume17
Issue number5
DOIs
StatePublished - May 1 2011

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Cladribine
Tablets
Multiple Sclerosis
Safety
Placebos
Herpes Zoster
Infection
Relapsing-Remitting Multiple Sclerosis
Lymphopenia
Incidence
Carcinoma in Situ
Neurologic Examination
Leiomyoma
Therapeutics
Double-Blind Method
Physical Examination
Neoplasms
Research Personnel

Keywords

  • Cladribine tablets
  • Disease-modifying therapy
  • Lymphopenia
  • Multiple sclerosis
  • Randomized controlled trial
  • Safety
  • Short-course therapy

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Medicine(all)

Cite this

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, Kottil W; Rieckmann, P.; Sørensen, P. Soelberg; Hamlett, A.; Miret, M.; Weiner, J.; Viglietta, V.; Musch, B.; Greenberg, S. J.

In: Multiple Sclerosis, Vol. 17, No. 5, 01.05.2011, p. 578-593.

Research output: Contribution to journalArticle

Cook, S, Vermersch, P, Comi, G, Giovannoni, G, Rammohan, KW, Rieckmann, P, Sørensen, PS, Hamlett, A, Miret, M, Weiner, J, Viglietta, V, Musch, B & Greenberg, SJ 2011, 'Safety and tolerability of cladribine tablets in multiple sclerosis: The CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study', Multiple Sclerosis, vol. 17, no. 5, pp. 578-593. https://doi.org/10.1177/1352458510391344
Cook, S. ; Vermersch, P. ; Comi, G. ; Giovannoni, G. ; Rammohan, Kottil W ; Rieckmann, P. ; Sørensen, P. Soelberg ; Hamlett, A. ; Miret, M. ; Weiner, J. ; Viglietta, V. ; Musch, B. ; Greenberg, S. J. / Safety and tolerability of cladribine tablets in multiple sclerosis : The CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study. In: Multiple Sclerosis. 2011 ; Vol. 17, No. 5. pp. 578-593.
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abstract = "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{\%}) cladribinetreated 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.",
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AU - Giovannoni, G.

AU - Rammohan, Kottil W

AU - Rieckmann, P.

AU - Sørensen, P. Soelberg

AU - Hamlett, A.

AU - Miret, M.

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