Efficacy of Cladribine Tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY study

In the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study, Cladribine Tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis. Describe two clinically relevant definitions for patien...

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Vydané v:Multiple sclerosis Ročník 25; číslo 6; s. 819
Hlavní autori: Giovannoni, Gavin, Soelberg Sorensen, Per, Cook, Stuart, Rammohan, Kottil W, Rieckmann, Peter, Comi, Giancarlo, Dangond, Fernando, Hicking, Christine, Vermersch, Patrick
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: England 01.05.2019
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Abstract In the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study, Cladribine Tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis. Describe two clinically relevant definitions for patients with high disease activity (HDA) at baseline of the CLARITY study (utility verified in patients receiving placebo) and assess the treatment effects of Cladribine Tablets 3.5 mg/kg compared with the overall study population. Outcomes of patients randomised to Cladribine Tablets 3.5 mg/kg or placebo were analysed for subgroups using HDA definitions based on high relapse activity (HRA; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not) or HRA plus disease activity on treatment (HRA + DAT; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not, PLUS patients with ⩾1 relapse during the year prior to study entry while on therapy with other DMDs and ⩾1 T1 Gd+ or ⩾9 T2 lesions). In the overall population, Cladribine Tablets 3.5 mg/kg reduced the risk of 6-month-confirmed Expanded Disability Status Scale (EDSS) worsening by 47% vs placebo. A risk reduction of 82% vs placebo was seen in both the HRA and HRA + DAT subgroups (vs 19% for non-HRA and 18% for non-HRA + DAT), indicating greater responsiveness to Cladribine Tablets 3.5 mg/kg in patients with HDA. There were consistent results for other efficacy endpoints. The safety profile in HDA patients was consistent with the overall CLARITY population. Patients with HDA showed clinical and MRI responses to Cladribine Tablets 3.5 mg/kg that were generally better than, or at least comparable with, the outcomes seen in the overall CLARITY population.
AbstractList In the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study, Cladribine Tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis.BACKGROUNDIn the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study, Cladribine Tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis.Describe two clinically relevant definitions for patients with high disease activity (HDA) at baseline of the CLARITY study (utility verified in patients receiving placebo) and assess the treatment effects of Cladribine Tablets 3.5 mg/kg compared with the overall study population.OBJECTIVEDescribe two clinically relevant definitions for patients with high disease activity (HDA) at baseline of the CLARITY study (utility verified in patients receiving placebo) and assess the treatment effects of Cladribine Tablets 3.5 mg/kg compared with the overall study population.Outcomes of patients randomised to Cladribine Tablets 3.5 mg/kg or placebo were analysed for subgroups using HDA definitions based on high relapse activity (HRA; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not) or HRA plus disease activity on treatment (HRA + DAT; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not, PLUS patients with ⩾1 relapse during the year prior to study entry while on therapy with other DMDs and ⩾1 T1 Gd+ or ⩾9 T2 lesions).METHODSOutcomes of patients randomised to Cladribine Tablets 3.5 mg/kg or placebo were analysed for subgroups using HDA definitions based on high relapse activity (HRA; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not) or HRA plus disease activity on treatment (HRA + DAT; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not, PLUS patients with ⩾1 relapse during the year prior to study entry while on therapy with other DMDs and ⩾1 T1 Gd+ or ⩾9 T2 lesions).In the overall population, Cladribine Tablets 3.5 mg/kg reduced the risk of 6-month-confirmed Expanded Disability Status Scale (EDSS) worsening by 47% vs placebo. A risk reduction of 82% vs placebo was seen in both the HRA and HRA + DAT subgroups (vs 19% for non-HRA and 18% for non-HRA + DAT), indicating greater responsiveness to Cladribine Tablets 3.5 mg/kg in patients with HDA. There were consistent results for other efficacy endpoints. The safety profile in HDA patients was consistent with the overall CLARITY population.RESULTSIn the overall population, Cladribine Tablets 3.5 mg/kg reduced the risk of 6-month-confirmed Expanded Disability Status Scale (EDSS) worsening by 47% vs placebo. A risk reduction of 82% vs placebo was seen in both the HRA and HRA + DAT subgroups (vs 19% for non-HRA and 18% for non-HRA + DAT), indicating greater responsiveness to Cladribine Tablets 3.5 mg/kg in patients with HDA. There were consistent results for other efficacy endpoints. The safety profile in HDA patients was consistent with the overall CLARITY population.Patients with HDA showed clinical and MRI responses to Cladribine Tablets 3.5 mg/kg that were generally better than, or at least comparable with, the outcomes seen in the overall CLARITY population.CONCLUSIONPatients with HDA showed clinical and MRI responses to Cladribine Tablets 3.5 mg/kg that were generally better than, or at least comparable with, the outcomes seen in the overall CLARITY population.
In the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study, Cladribine Tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis. Describe two clinically relevant definitions for patients with high disease activity (HDA) at baseline of the CLARITY study (utility verified in patients receiving placebo) and assess the treatment effects of Cladribine Tablets 3.5 mg/kg compared with the overall study population. Outcomes of patients randomised to Cladribine Tablets 3.5 mg/kg or placebo were analysed for subgroups using HDA definitions based on high relapse activity (HRA; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not) or HRA plus disease activity on treatment (HRA + DAT; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not, PLUS patients with ⩾1 relapse during the year prior to study entry while on therapy with other DMDs and ⩾1 T1 Gd+ or ⩾9 T2 lesions). In the overall population, Cladribine Tablets 3.5 mg/kg reduced the risk of 6-month-confirmed Expanded Disability Status Scale (EDSS) worsening by 47% vs placebo. A risk reduction of 82% vs placebo was seen in both the HRA and HRA + DAT subgroups (vs 19% for non-HRA and 18% for non-HRA + DAT), indicating greater responsiveness to Cladribine Tablets 3.5 mg/kg in patients with HDA. There were consistent results for other efficacy endpoints. The safety profile in HDA patients was consistent with the overall CLARITY population. Patients with HDA showed clinical and MRI responses to Cladribine Tablets 3.5 mg/kg that were generally better than, or at least comparable with, the outcomes seen in the overall CLARITY population.
Author Vermersch, Patrick
Soelberg Sorensen, Per
Giovannoni, Gavin
Hicking, Christine
Cook, Stuart
Rieckmann, Peter
Dangond, Fernando
Rammohan, Kottil W
Comi, Giancarlo
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  surname: Giovannoni
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  givenname: Per
  surname: Soelberg Sorensen
  fullname: Soelberg Sorensen, Per
  organization: Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
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  surname: Cook
  fullname: Cook, Stuart
  organization: Department of Neurology & Neurosciences, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA
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  givenname: Kottil W
  surname: Rammohan
  fullname: Rammohan, Kottil W
  organization: MS Research Center, Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA
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  givenname: Peter
  surname: Rieckmann
  fullname: Rieckmann, Peter
  organization: Department of Neurology, Hospital for Nervous Diseases, Medical Park Loipl, Bischofswiesen, Germany/University of Erlangen-Nürnberg, Erlangen, Germany
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  givenname: Giancarlo
  surname: Comi
  fullname: Comi, Giancarlo
  organization: Department of Neurology, Università Vita-Salute San Raffaele and Institute of Experimental Neurology, Ospedale San Raffaele, Milan, Italy
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  givenname: Fernando
  surname: Dangond
  fullname: Dangond, Fernando
  organization: EMD Serono, Inc., Billerica, MA, USA
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  surname: Hicking
  fullname: Hicking, Christine
  organization: Merck KGaA, Darmstadt, Germany
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  givenname: Patrick
  surname: Vermersch
  fullname: Vermersch, Patrick
  organization: University of Lille, CHU Lille, LIRIC-INSERM U995, FHU Imminent, Lille, France
BackLink https://www.ncbi.nlm.nih.gov/pubmed/29716436$$D View this record in MEDLINE/PubMed
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high disease activity
safety
efficacy
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PublicationTitle Multiple sclerosis
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Snippet In the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study, Cladribine Tablets significantly improved clinical and magnetic resonance imaging...
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SubjectTerms Adult
Cladribine - administration & dosage
Cladribine - adverse effects
Cladribine - pharmacology
Disease Progression
Female
Humans
Immunosuppressive Agents - administration & dosage
Immunosuppressive Agents - adverse effects
Immunosuppressive Agents - pharmacology
Magnetic Resonance Imaging
Male
Middle Aged
Multiple Sclerosis, Relapsing-Remitting - diagnostic imaging
Multiple Sclerosis, Relapsing-Remitting - drug therapy
Multiple Sclerosis, Relapsing-Remitting - physiopathology
Outcome Assessment, Health Care
Severity of Illness Index
Title Efficacy of Cladribine Tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY study
URI https://www.ncbi.nlm.nih.gov/pubmed/29716436
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