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Link to original content: http://pubmed.ncbi.nlm.nih.gov/29716436/
Efficacy of Cladribine Tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY study - PubMed Skip to main page content
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Randomized Controlled Trial
. 2019 May;25(6):819-827.
doi: 10.1177/1352458518771875. Epub 2018 May 2.

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

Gavin Giovannoni  1 , Per Soelberg Sorensen  2 , Stuart Cook  3 , Kottil W Rammohan  4 , Peter Rieckmann  5 , Giancarlo Comi  6 , Fernando Dangond  7 , Christine Hicking  8 , Patrick Vermersch  9
Affiliations
Randomized Controlled Trial

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

Gavin Giovannoni et al. Mult Scler. 2019 May.

Abstract

Background: 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.

Objective: 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.

Methods: 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).

Results: 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.

Conclusion: 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.

Keywords: Cladribine Tablets; efficacy; high disease activity; risk:benefit; safety.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: G.G. has received speaker honoraria and consulting fees from Abbvie, Atara Bio, Almirall, Bayer Schering Pharma, Biogen Idec FivePrime, GlaxoSmithKline, GW Pharma, Merck, Pfizer Inc, Protein Discovery Laboratories, Teva Pharmaceutical Industries Ltd, Sanofi-Genzyme, UCB, Vertex Pharmaceuticals, Ironwood and Novartis and has received research support unrelated to this study from Biogen Idec, Merck, Novartis and Ironwood. P.S.S. has served on the advisory boards for Biogen, Merck, Novartis, Teva, MedDay Pharmaceuticals and GSK; on steering committees or independent data-monitoring boards in trials sponsored by Merck, Teva, GSK and Novartis and has received speaker honoraria from Biogen Idec, Merck, Teva, Sanofi-Aventis, Genzyme and Novartis. His department has received research support from Biogen, Merck, Teva, Novartis, Roche and Genzyme. S.C. has received honoraria for lectures/consultations from Merck, Bayer HealthCare, Sanofi-Aventis, Neurology Reviews, Biogen Idec, Teva Pharmaceuticals and Actinobac Biomed Inc; has served on the advisory boards for Bayer HealthCare, Merck, Actinobac Biomed, Teva Pharmaceuticals and Biogen Idec and received grant support from Bayer HealthCare. K.W.R. has received honoraria for lectures and steering committee meetings from EMD Serono, Biogen Idec, Sanofi-Aventis, Genzyme, Novartis, Teva Neurosciences, Acorda and Roche/Genentech. P.R. has received honoraria for lectures/steering committee meetings from Merck, Biogen Idec, Bayer Schering Pharma, Boehringer-Ingelheim, Sanofi-Aventis, Genzyme, Novartis, Teva Pharmaceutical Industries and Serono Symposia International Foundation. G.C. has received consulting fees from Novartis, Teva Pharmaceutical Industries Ltd, Sanofi-Aventis, Merck, Receptors, Biogen Idec, Genentech-Roche and Bayer Schering; lecture fees from Novartis, Teva Pharmaceutical Industries Ltd, Sanofi-Aventis, Merck, Biogen Dompè, Bayer Schering and Serono Symposia International Foundation and trial grant support from Novartis, Teva Pharmaceutical Industries Ltd, Sanofi-Aventis, Receptors, Biogen Idec, Genentech-Roche, Merck, Biogen Dompè and Bayer Schering. F.D. is an employee of EMD Serono, Inc, Billerica, USA, a business of Merck KGaA, Darmstadt, Germany. C.H. is an employee of Merck KGaA, Darmstadt, Germany. P.V. has received honoraria or consulting fees from Biogen, Sanofi-Genzyme, Bayer, Novartis, Merck, GSK, Roche, Servier and Almirall and research support from Biogen, Sanofi-Genzyme, Bayer and Merck.

Figures

Figure 1.
Figure 1.
Definitions used for the HRA and HRA + DAT subgroups. DMD: disease modifying drug; DAT: disease activity on treatment; HRA: high relapse activity; HRA+DAT: high relapse activity plus disease activity on treatment.
Figure 2.
Figure 2.
Forest plot of hazard ratio of time to 6-month-confirmed EDSS worsening by HDA subgroup for Cladribine Tablets 3.5 mg/kg vs placebo. EDSS: Expanded Disability Status Scale; HDA: high disease activity; HRA: high relapse activity; HRA+DAT: high relapse activity plus disease activity on treatment.
Figure 3.
Figure 3.
Forest plot of relative risk of ARR by HDA subgroup for Cladribine Tablets 3.5 mg/kg vs placebo. ARR: Annualised Relapse Rate; HDA: high disease activity; HRA: high relapse activity; HRA + DAT: high relapse activity plus disease activity on treatment.
Figure 4.
Figure 4.
Forest plot of relative risk of cumulative number of new T1 Gd+ lesions by HDA subgroups for Cladribine Tablets 3.5 mg/kg vs placebo. Gd+; gadolinium enhancing; HDA: high disease activity; HRA: high relapse activity; HRA+DAT: high relapse activity plus disease activity on treatment.
Figure 5.
Figure 5.
Forest plot of odds ratio of NEDA score by HDA subgroups for Cladribine Tablets 3.5 mg/kg vs placebo. Gd+; gadolinium enhancing; HDA: high disease activity; HRA: high relapse activity; HRA+DAT: high relapse activity plus disease activity on treatment; NEDA: no evidence of disease activity (defined as no relapses, no 3-month confirmed EDSS worsening, no T1 Gd+ lesions and no active T2 lesions).
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