26 de abril de 2019
  • Jueves, 25 de Abril
  • 16 de abril de 2010

    New Data Supporting Cladribine Tablets as a Potential New Therapeutic Option Presented at the 62nd AAN Annual Meeting (1


    - Increase in the proportion of patients with disease activity-free
    status compared with the placebo group over the entire 96-week study
    (43% and 44% of patients treated with Cladribine Tablets total dose
    of 3.5 mg/kg and 5.25 mg/kg respectively compared with 16% of patients
    who received placebo - p<0.001 for both Cladribine Tablets groups) with
    statistically significant findings as early as 24 weeks (67% and 70%
    of patients treated with Cladribine Tablets total dose of 3.5 mg/kg and
    5.25 mg/kg respectively compared with 39% of patients who received
    placebo - p<0.001 for both Cladribine Tablets groups). Disease
    activity-free status was defined as having no clinical activity (no
    relapse and no sustained disability progression) and no radiological
    activity (no T1 Gd+ lesions and no active T2 lesions) over the
    96-week study(1)
    .
    - Reductions in annualized relapse rate (ARR) compared to the placebo
    group over 96 weeks across the spectrum of baseline demographics and
    disease characteristics included in the CLARITY study (gender, age,
    treatment history, number of relapses in the 12 months preceding study
    entry, baseline disease disability, baseline MRI activity and burden
    of disease)(2)
    - Reduced consumption of healthcare resources, a decreased need for
    societal support, improvements in patient productivity, and reductions
    in total non-drug expenditure, relative to placebo, as measured by
    data collected in the CLARITY study with a 'resource utilization form'
    at baseline and at scheduled patient visits(3)
    .
    - Decrease of proportions of circulating CD4+ T cells relative to the
    total number of lymphocytes at the end of treatment periods compared
    to baseline, while the proportions of other lymphocyte subtypes
    (CD8+ T, B and natural killer cells) were preserved or increased
    relative to total lymphocytes.(4)

    Overall, the frequencies of adverse events by MedDRA System Organ Class in both Cladribine Tablets treatment groups from the CLARITY study were comparable to those observed in the placebo group. The most commonly reported adverse events were headaches, upper respiratory tract infection, nasopharyngitis and nausea. Lymphopenia, an expected event based on the presumed mechanism of action of cladribine, occurred more frequently in the Cladribine Tablets treatment groups (3,5 mg/kg total dose: 21.6%; 5.25 mg/kg total dose: 31.5%; placebo: 1.8%). The overall rate and incidence of infections in patients treated with Cladribine Tablets and placebo were similar. Herpes zoster infections were reported in 2.3% of patients treated with Cladribine Tablets. These herpes infections were localized to the skin and responded appropriately to treatment.

    (a) CLARITY: CLAdRIbine Tablets Treating MS OrallY

    References:

    (1) Analysis of Clinical and Radiological Disease Activity-Free Status in Patients with Relapsing-Remitting Multiple Sclerosis (RRMS) Treated with Cladribine Tablets, in the Double-Blind, 96-Week CLARITY Study (presentation S21.008, Wednesday, April 14, 2010, 3:45 pm EDT)

    (2) Consistent Efficacy of Cladribine Tablets across Multiple Sclerosis and Patient Characteristics, in the Double-Blind, 96-Week CLARITY Study (poster P02.186, Tuesday, April 13, 2010, 3:00 pm-7:30 pm EDT)

    Reductions in the annualized relapse rate (ARR) across the various patient strata:

    [TAB]

    - Gender (man or woman): Relative reductions in ARR were 61% and 55%,

    respectively, for 3.5 mg/kg and 68% and 48%, respectively, for

    5.25 mg/kg (all p<0.001 versus placebo)

    - Age (=40 or >40): Relative reductions in ARR were 58% and 57%,

    respectively, for 3.5 mg/kg and 63% and 46%, respectively, for

    5.25 mg/kg (all p<0.001 versus placebo)

    - Treatment history (previously treated with disease-modifying therapy

    or drug-naïve patients): Relative reductions in ARR were 45% and 61%,

    respectively, for 3.5 mg/kg and 58% and 58%, respectively for

    5.25 mg/kg (all p=0.0013 versus placebo)

    - Number of relapses in the 12 months preceding study entry (=1, 2 or

    =3 relapses): Relative reductions in ARR ranged from 48% (relative

    risk: 0.50; 95% confidence interval: 0.37, 0.66) to 76% (relative

    risk: 0.24; 95% confidence interval: 0.09, 0.64) depending on dose

    group (all p=0.006 versus placebo)

    - Level of disability at baseline (EDSS 0-2.5 or EDSS =3): Relative

    reductions in ARR ranged from 49% (relative risk: 0.51; 95%

    confidence interval: 0.38, 0.68) to 65% (relative risk: 0.35; 95%

    confidence interval: 0.25, 0.50) depending on dose group (all p<0.001

    versus placebo)

    - T1 Gd+ lesions (no lesions or =1 lesion): Relative reductions in ARR

    ranged from 45% (relative risk: 0.55; 95% confidence interval: 0.42,

    0.72) to 75% (relative risk: 0.26; 95% confidence interval: 0.17, 0.40)

    depending on dose group (all p<0.001 versus placebo)

    - T2 lesion volume (>or = median T2 lesion volume status): Relative

    reductions in ARR ranged from 48% (relative risk: 0.53; 95% confidence

    interval: 0.39, 0.71) to 67% (relative risk: 0.33; 95% confidence

    interval: 0.24, 0.47) depending on dose group (all p<0.001

    versus placebo)

    [FTAB]

    (3) Health Resource Utilization in the CLARITY Study (poster P01.205, Tuesday, April 13, 2010, 7:30 am-12:00 pm EDT)

    (4) Effects of Cladribine Tablets on Circulating Lymphocyte Subsets in the 96-Week CLARITY Study in Relapsing-Remitting Multiple Sclerosis (RRMS) (poster P04.219, Wednesday, April 14, 2010, 3:00 pm-7:30 pm EDT)

    CLARITY study design

    (CONTINUA)


    - Gender (man or woman): Relative reductions in ARR were 61% and 55%,
    respectively, for 3.5 mg/kg and 68% and 48%, respectively, for
    5.25 mg/kg (all p<0.001 versus placebo)
    - Age (=40 or >40): Relative reductions in ARR were 58% and 57%,
    respectively, for 3.5 mg/kg and 63% and 46%, respectively, for
    5.25 mg/kg (all p<0.001 versus placebo)
    - Treatment history (previously treated with disease-modifying therapy
    or drug-naïve patients): Relative reductions in ARR were 45% and 61%,
    respectively, for 3.5 mg/kg and 58% and 58%, respectively for
    5.25 mg/kg (all p=0.0013 versus placebo)
    - Number of relapses in the 12 months preceding study entry (=1, 2 or
    =3 relapses): Relative reductions in ARR ranged from 48% (relative
    risk: 0.50; 95% confidence interval: 0.37, 0.66) to 76% (relative
    risk: 0.24; 95% confidence interval: 0.09, 0.64) depending on dose
    group (all p=0.006 versus placebo)
    - Level of disability at baseline (EDSS 0-2.5 or EDSS =3): Relative
    reductions in ARR ranged from 49% (relative risk: 0.51; 95%
    confidence interval: 0.38, 0.68) to 65% (relative risk: 0.35; 95%
    confidence interval: 0.25, 0.50) depending on dose group (all p<0.001
    versus placebo)
    - T1 Gd+ lesions (no lesions or =1 lesion): Relative reductions in ARR
    ranged from 45% (relative risk: 0.55; 95% confidence interval: 0.42,
    0.72) to 75% (relative risk: 0.26; 95% confidence interval: 0.17, 0.40)
    depending on dose group (all p<0.001 versus placebo)
    - T2 lesion volume (>or = median T2 lesion volume status): Relative
    reductions in ARR ranged from 48% (relative risk: 0.53; 95% confidence
    interval: 0.39, 0.71) to 67% (relative risk: 0.33; 95% confidence
    interval: 0.24, 0.47) depending on dose group (all p<0.001
    versus placebo)

    (3) Health Resource Utilization in the CLARITY Study (poster P01.205, Tuesday, April 13, 2010, 7:30 am-12:00 pm EDT)

    (4) Effects of Cladribine Tablets on Circulating Lymphocyte Subsets in the 96-Week CLARITY Study in Relapsing-Remitting Multiple Sclerosis (RRMS) (poster P04.219, Wednesday, April 14, 2010, 3:00 pm-7:30 pm EDT)

    CLARITY study design

    (CONTINUA)