PMID- 21228029
OWN - NLM
STAT- MEDLINE
DCOM- 20111004
LR  - 20220408
IS  - 1477-0970 (Electronic)
IS  - 1352-4585 (Linking)
VI  - 17
IP  - 5
DP  - 2011 May
TI  - Safety and tolerability of cladribine tablets in multiple sclerosis: the CLARITY 
      (CLAdRIbine Tablets treating multiple sclerosis orallY) study.
PG  - 578-93
LID - 10.1177/1352458510391344 [doi]
AB  - 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.
FAU - Cook, S
AU  - Cook S
AD  - University of Medicine and Dentistry, New Jersey Medical School, Newark, NJ 
      07101, USA. cooksd@umdnj.edu
FAU - Vermersch, P
AU  - Vermersch P
FAU - Comi, G
AU  - Comi G
FAU - Giovannoni, G
AU  - Giovannoni G
FAU - Rammohan, K
AU  - Rammohan K
FAU - Rieckmann, P
AU  - Rieckmann P
FAU - Sorensen, P Soelberg
AU  - Sorensen PS
FAU - Hamlett, A
AU  - Hamlett A
FAU - Miret, M
AU  - Miret M
FAU - Weiner, J
AU  - Weiner J
FAU - Viglietta, V
AU  - Viglietta V
FAU - Musch, B
AU  - Musch B
FAU - Greenberg, S J
AU  - Greenberg SJ
CN  - CLARITY Study Group
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20110112
PL  - England
TA  - Mult Scler
JT  - Multiple sclerosis (Houndmills, Basingstoke, England)
JID - 9509185
RN  - 0 (Immunosuppressive Agents)
RN  - 47M74X9YT5 (Cladribine)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Cladribine/administration & dosage/*adverse effects
MH  - Disability Evaluation
MH  - Double-Blind Method
MH  - Europe
MH  - Herpes Zoster/chemically induced
MH  - Humans
MH  - Immunosuppressive Agents/administration & dosage/*adverse effects
MH  - Lymphopenia/chemically induced
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis, Relapsing-Remitting/diagnosis/*drug therapy
MH  - Neoplasms/chemically induced
MH  - Neurologic Examination
MH  - Physical Examination
MH  - Risk Assessment
MH  - Risk Factors
MH  - Time Factors
MH  - Treatment Outcome
MH  - United States
MH  - Young Adult
EDAT- 2011/01/14 06:00
MHDA- 2011/10/05 06:00
CRDT- 2011/01/14 06:00
PHST- 2011/01/14 06:00 [entrez]
PHST- 2011/01/14 06:00 [pubmed]
PHST- 2011/10/05 06:00 [medline]
AID - 1352458510391344 [pii]
AID - 10.1177/1352458510391344 [doi]
PST - ppublish
SO  - Mult Scler. 2011 May;17(5):578-93. doi: 10.1177/1352458510391344. Epub 2011 Jan 
      12.