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The Development of Cladribine Tablets for the Treatment of Multiple Sclerosis: A Comprehensive Review
Cladribine is a purine nucleoside analog initially developed in the 1970s as a treatment for various blood cancers. Due to the molecule’s ability to preferentially reduce T and B lymphocytes, it has been developed into an oral formulation for the treatment of multiple sclerosis (MS). The unique prop...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer International Publishing
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708385/ https://www.ncbi.nlm.nih.gov/pubmed/33247831 http://dx.doi.org/10.1007/s40265-020-01422-9 |
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author | Rammohan, Kottil Coyle, Patricia K. Sylvester, Elke Galazka, Andrew Dangond, Fernando Grosso, Megan Leist, Thomas P. |
author_facet | Rammohan, Kottil Coyle, Patricia K. Sylvester, Elke Galazka, Andrew Dangond, Fernando Grosso, Megan Leist, Thomas P. |
author_sort | Rammohan, Kottil |
collection | PubMed |
description | Cladribine is a purine nucleoside analog initially developed in the 1970s as a treatment for various blood cancers. Due to the molecule’s ability to preferentially reduce T and B lymphocytes, it has been developed into an oral formulation for the treatment of multiple sclerosis (MS). The unique proposed mechanism of action of cladribine allows for the therapy to be delivered orally over two treatment-week cycles per year, one cycle at the beginning of the first month and one cycle at the beginning of the second month of years 1 and 2, with the potential for no further cladribine treatment required in years 3 and 4. This review summarizes the clinical development program for cladribine tablets in patients with MS, including the efficacy endpoints and results from the 2-year phase III CLARITY study in patients with relapsing–remitting MS (RRMS), the 2-year CLARITY EXTENSION study, and the phase III ORACLE-MS study in patients with a first clinical demyelinating event at risk for developing MS. Efficacy results from the phase II ONWARD study, in which cladribine tablets were administered as an add-on to interferon-β therapy in patients with RRMS, are also summarized. A review of all safety data, including lymphopenia, infections, and malignancies, is provided based on data from all trials in patients with MS, including the initial parenteral formulation studies. Based on these data, cladribine tablets administered at 3.5 mg/kg over 2 years have been approved across the globe for various forms of relapsing MS. Enhanced Digital Features To view enhanced digital features for this article, go to 10.1007/s40265-020-01422-9 |
format | Online Article Text |
id | pubmed-7708385 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-77083852020-12-03 The Development of Cladribine Tablets for the Treatment of Multiple Sclerosis: A Comprehensive Review Rammohan, Kottil Coyle, Patricia K. Sylvester, Elke Galazka, Andrew Dangond, Fernando Grosso, Megan Leist, Thomas P. Drugs Review Article Cladribine is a purine nucleoside analog initially developed in the 1970s as a treatment for various blood cancers. Due to the molecule’s ability to preferentially reduce T and B lymphocytes, it has been developed into an oral formulation for the treatment of multiple sclerosis (MS). The unique proposed mechanism of action of cladribine allows for the therapy to be delivered orally over two treatment-week cycles per year, one cycle at the beginning of the first month and one cycle at the beginning of the second month of years 1 and 2, with the potential for no further cladribine treatment required in years 3 and 4. This review summarizes the clinical development program for cladribine tablets in patients with MS, including the efficacy endpoints and results from the 2-year phase III CLARITY study in patients with relapsing–remitting MS (RRMS), the 2-year CLARITY EXTENSION study, and the phase III ORACLE-MS study in patients with a first clinical demyelinating event at risk for developing MS. Efficacy results from the phase II ONWARD study, in which cladribine tablets were administered as an add-on to interferon-β therapy in patients with RRMS, are also summarized. A review of all safety data, including lymphopenia, infections, and malignancies, is provided based on data from all trials in patients with MS, including the initial parenteral formulation studies. Based on these data, cladribine tablets administered at 3.5 mg/kg over 2 years have been approved across the globe for various forms of relapsing MS. Enhanced Digital Features To view enhanced digital features for this article, go to 10.1007/s40265-020-01422-9 Springer International Publishing 2020-11-28 2020 /pmc/articles/PMC7708385/ /pubmed/33247831 http://dx.doi.org/10.1007/s40265-020-01422-9 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Review Article Rammohan, Kottil Coyle, Patricia K. Sylvester, Elke Galazka, Andrew Dangond, Fernando Grosso, Megan Leist, Thomas P. The Development of Cladribine Tablets for the Treatment of Multiple Sclerosis: A Comprehensive Review |
title | The Development of Cladribine Tablets for the Treatment of Multiple Sclerosis: A Comprehensive Review |
title_full | The Development of Cladribine Tablets for the Treatment of Multiple Sclerosis: A Comprehensive Review |
title_fullStr | The Development of Cladribine Tablets for the Treatment of Multiple Sclerosis: A Comprehensive Review |
title_full_unstemmed | The Development of Cladribine Tablets for the Treatment of Multiple Sclerosis: A Comprehensive Review |
title_short | The Development of Cladribine Tablets for the Treatment of Multiple Sclerosis: A Comprehensive Review |
title_sort | development of cladribine tablets for the treatment of multiple sclerosis: a comprehensive review |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708385/ https://www.ncbi.nlm.nih.gov/pubmed/33247831 http://dx.doi.org/10.1007/s40265-020-01422-9 |
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