Kottil Rammohan1, Gavin Giovannoni2, Giancarlo Comi3, Stuart Cook4, Peter Rieckmann5, Per Soelberg Sørensen6, Patrick Vermersch7, Anthony Hamlett8, Nuwan Kurukulasuriya9. 1. Multiple Sclerosis Center, Department of Neurology, Clinical Research Building, 1120 NW 14th Street, 13th Floor, Miami, FL 33136, USA. Electronic address: KRammohan@med.miami.edu. 2. Queen Mary University London, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, 4 Newark Street, Whitechapel, London E1 2AT, UK. Electronic address: g.giovannoni@qmul.ac.uk. 3. Department of Neurology and Institute of Experimental Neurology Università Vita-Salute San Raffaele, Via Olgettina 48, 20132 Milan, Italy. Electronic address: comi.giancarlo@hsr.it. 4. University of Medicine and Dentistry, New Jersey Medical School, 65 Bergen Street, Newark, NJ 07101, USA. Electronic address: cooksd@umdnj.edu. 5. Bamberg Academic Hospital, University of Erlangen, Buger Strasse 80, D-96049 Bamberg, Germany. Electronic address: peter.rieckmann@sozialstiftung-bamberg.de. 6. Copenhagen University Hospital, Rigshospitalet, 9, Blegdamsvej, DK-2100 Copenhagen, Denmark. Electronic address: pss@rh.dk. 7. University of Lille-Nord de France, Pole de Neurolgie, Hopital R Salergro, CHU de Lille 59037, Lille, France. Electronic address: PVERMERSCH@CHRU-LILLE.FR. 8. Merck Serono SA-Geneva, 9 Chemin de Mines,1202 Geneva, Switzerland. Electronic address: anthony.hamlett@emdserono.com. 9. Merck Serono SA-Geneva, 9 Chemin de Mines,1202 Geneva, Switzerland. Electronic address: nuwan.kurukulasuriya@emdserono.com.
Abstract
BACKGROUND: In the phase III CLARITY study, treatment with cladribine tablets at cumulative doses of 3.5 or 5.25mg/kg over 96 weeks led to significant reductions in annualized relapse rates (ARR) versus placebo in patients with relapsing-remitting multiple sclerosis. Further post hoc analyses of CLARITY study data were conducted to determine the efficacy of cladribine tablets across patient subgroups stratified by baseline characteristics. METHODS:Relapse rates over the 96-week CLARITY study were analyzed in cohorts stratified by demographics; disease duration; treatment history and disease activity at baseline. RESULTS: In the intent-to-treat population (n=437, 433 and 456 in the placebo, cladribine 3.5 and 5.25mg/kg groups, respectively), treatment with cladribine tablets 3.5 and 5.25mg/kg led to consistent improvements in ARR versus placebo in patients stratified by gender; age (≤40/>40 years); disease duration (<3/3-10/>10 years); prior disease-modifying drug treatment (treated/naïve); relapses in the prior year (≤1/2/≥3); Expanded Disability Status Scale score (<3.5/≥3.5); T1 gadolinium-enhancing lesions (presence, absence); and T2 lesion volume (≤median/>median) at baseline (all P≤0.05 for reduction in the relative risk of relapse [cladribine tablets versus placebo]). Significant effects were also observed in patients who had only one relapse in the year prior to study entry (n=306, 303 and 323 in the placebo, cladribine 3.5 and 5.25mg/kg groups, respectively) and who were further stratified according to other measures of disease activity at baseline. CONCLUSIONS: Treatment with cladribine tablets provides consistent reductions in ARR compared with placebo across the spectrum of baseline demographics and disease characteristics represented in the CLARITY study.
RCT Entities:
BACKGROUND: In the phase III CLARITY study, treatment with cladribine tablets at cumulative doses of 3.5 or 5.25mg/kg over 96 weeks led to significant reductions in annualized relapse rates (ARR) versus placebo in patients with relapsing-remitting multiple sclerosis. Further post hoc analyses of CLARITY study data were conducted to determine the efficacy of cladribine tablets across patient subgroups stratified by baseline characteristics. METHODS: Relapse rates over the 96-week CLARITY study were analyzed in cohorts stratified by demographics; disease duration; treatment history and disease activity at baseline. RESULTS: In the intent-to-treat population (n=437, 433 and 456 in the placebo, cladribine 3.5 and 5.25mg/kg groups, respectively), treatment with cladribine tablets 3.5 and 5.25mg/kg led to consistent improvements in ARR versus placebo in patients stratified by gender; age (≤40/>40 years); disease duration (<3/3-10/>10 years); prior disease-modifying drug treatment (treated/naïve); relapses in the prior year (≤1/2/≥3); Expanded Disability Status Scale score (<3.5/≥3.5); T1 gadolinium-enhancing lesions (presence, absence); and T2 lesion volume (≤median/>median) at baseline (all P≤0.05 for reduction in the relative risk of relapse [cladribine tablets versus placebo]). Significant effects were also observed in patients who had only one relapse in the year prior to study entry (n=306, 303 and 323 in the placebo, cladribine 3.5 and 5.25mg/kg groups, respectively) and who were further stratified according to other measures of disease activity at baseline. CONCLUSIONS: Treatment with cladribine tablets provides consistent reductions in ARR compared with placebo across the spectrum of baseline demographics and disease characteristics represented in the CLARITY study.
Authors: Mark S Freedman; Staley Brod; Barry A Singer; Bruce A Cohen; Brooke Hayward; Fernando Dangond; Patricia K Coyle Journal: J Neurol Date: 2019-09-26 Impact factor: 4.849
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