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

Mult Scler. 2011 May;17(5):578-93. doi: 10.1177/1352458510391344. Epub 2011 Jan 12.


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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Immunosuppressive Agents
  • Cladribine