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      Efficacy of Cladribine Tablets as a Treatment for People With Multiple Sclerosis: Protocol for the CLOBAS Study (Cladribine, a Multicenter, Long-term Efficacy and Biomarker Australian Study)


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          Cladribine tablets (marketed as Mavenclad) are a new oral therapy, which has recently been listed on the pharmaceutical benefits scheme in Australia for the treatment of relapsing multiple sclerosis (MS). The current dosing schedule is for 2 courses given a year apart, which has been shown to be effective for treatment of MS for up to 4 years in 75% of patients (based on annualized relapse rate). However, the reinitiation of therapy after year 4 has not been studied.


          This study aims to evaluate the safety and efficacy of cladribine tablets over a 6-year period, according to no evidence of disease activity 3.


          This will be a multicenter, 6-year, phase IV, low interventional, observational study that incorporates clinical, hematological, biochemical, epigenetic, radiological and cognitive biomarkers of disease. Participants considered for treatment with cladribine as part of their routine clinical care will be consented to take part in the study. They will be monitored at regular intervals during the initial course of medication administration in years 1 and 2. After year 3, patients will have the option of redosing, if clinically indicated, or to switch to another disease-modifying therapy. Throughout the duration of the study, we will assess blood-based biomarkers including lymphocyte subsets, serum neurofilament light chain, DNA methylation, and RNA analysis as well as magnetic resonance imaging findings (brain volume and/or lesion load) and cognitive performance.


          This study has been approved by the Hunter New England Local Health District Human Research Ethics Committee. Recruitment began in March of 2019 and was completed by June 2021.


          This will be the first long-term efficacy trial of cladribine, which offers reinitiation of therapy in the 3rd year, based on disease activity, after the initial 2 courses. We expect that this study will indicate whether any of the assessed biomarkers can be used to predict treatment efficacy or the need for future reinitiation of cladribine in people with MS.

          Trial Registration

          This study is registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12619000257167) with Universal Trial Number (U1111-1228-2165).

          International Registered Report Identifier (IRRID)


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          Most cited references57

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          Regularization Paths for Generalized Linear Models via Coordinate Descent

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            Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria

            The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation. The following changes were made: in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space, the presence of CSF-specific oligoclonal bands allows a diagnosis of multiple sclerosis; symptomatic lesions can be used to demonstrate dissemination in space or time in patients with supratentorial, infratentorial, or spinal cord syndrome; and cortical lesions can be used to demonstrate dissemination in space. Research to further refine the criteria should focus on optic nerve involvement, validation in diverse populations, and incorporation of advanced imaging, neurophysiological, and body fluid markers.
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              Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis

              B cells influence the pathogenesis of multiple sclerosis. Ocrelizumab is a humanized monoclonal antibody that selectively depletes CD20+ B cells.

                Author and article information

                JMIR Res Protoc
                JMIR Res Protoc
                JMIR Research Protocols
                JMIR Publications (Toronto, Canada )
                October 2021
                19 October 2021
                : 10
                : 10
                : e24969
                [1 ] Department of Neurology John Hunter Hospital New Lambton Heights Australia
                [2 ] School for Medicine and Public Health University of Newcastle Callaghan Australia
                [3 ] Hunter Medical Research Institute New Lambton Heights Australia
                [4 ] Institute of Health and Biomedical Innovations Genomics Research Centre Queensland University of Technology Kelvin Grove Australia
                [5 ] Department of Neurosciences, Eastern Health Clinical School Monash University Box Hill Hospital Melbourne Australia
                [6 ] Department of Neurology Alfred Health Melbourne Australia
                [7 ] Department of Neurology Melbourne Multiple Sclerosis Centre Melbourne Health Melbourne Australia
                [8 ] Centre for Neuromuscular and Neurological Disorders Perron Institute for Neurological and Translational Science University of Western Australia Perth Australia
                [9 ] Clinical Outcomes Research (CORe) Unit Department of Medicine University of Melbourne Melbourne Australia
                [10 ] Institute for Immunology and Infectious Disease Murdoch University Perth Australia
                [11 ] Menzies Institute for Medical Research University of Tasmania Hobart Australia
                [12 ] Department of Medicine University of New South Wales Sydney Australia
                [13 ] Department of Neurology Liverpool Hospital Sydney Australia
                [14 ] Immune Tolerance Laboratory Ingham Institute Sydney Australia
                [15 ] Centre for Clinical Research University of Queensland Brisbane Australia
                [16 ] Brain and Mind Centre University of Sydney Sydney Australia
                [17 ] Sydney Neuroimaging Analysis Centre Sydney Australia
                Author notes
                Corresponding Author: Jeannette Lechner-Scott jeannette.lechner-scott@ 123456health.nsw.gov.au
                Author information
                ©Vicki E Maltby, Rodney A Lea, Mastura Monif, Marzena J Fabis-Pedrini, Katherine Buzzard, Tomas Kalincik, Allan G Kermode, Bruce Taylor, Suzanne Hodgkinson, Pamela McCombe, Helmut Butzkueven, Michael Barnett, Jeannette Lechner-Scott. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 19.10.2021.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Research Protocols, is properly cited. The complete bibliographic information, a link to the original publication on https://www.researchprotocols.org, as well as this copyright and license information must be included.

                : 12 October 2020
                : 12 March 2021
                : 4 May 2021
                : 28 May 2021

                multiple sclerosis,cladribine,biomarkers
                multiple sclerosis, cladribine, biomarkers


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