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

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%) 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.

• Authors: S Cook, P Vermersch, G Comi, G Giovannoni, K Rammohan, P Rieckmann, P Soelberg Sørensen, A Hamlett, M Miret, J Weiner, V Viglietta, B Musch, S J Greenberg, CLARITY Study Group
• Journal: Multiple sclerosis (Houndmills, Basingstoke, England) (Mult Scler) Vol. 17 Issue 5 Pg. 578-93 (May 2011) ISSN: 1477-0970 [Electronic] England
• PMID: 21228029 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Immunosuppressive Agents
• Cladribine

Topics

• Administration, Oral
• Adult
• Cladribine (administration & dosage, adverse effects)
• Disability Evaluation
• Double-Blind Method
• Europe
• Herpes Zoster (chemically induced)
• Humans
• Immunosuppressive Agents (administration & dosage, adverse effects)
• Lymphopenia (chemically induced)
• Male
• Middle Aged
• Multiple Sclerosis, Relapsing-Remitting (diagnosis, drug therapy)
• Neoplasms (chemically induced)
• Neurologic Examination
• Physical Examination
• Risk Assessment
• Risk Factors
• Time Factors
• Treatment Outcome
• United States
• Young Adult