Predictors of oral cladribine effectiveness and safety in multiple sclerosis patients Review article
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Published:
Mar 31, 2023
Keywords:
highly active therapies, oral cladribine, long-term efficacy, predictors
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Abstract
Currently, the most desirable scenario in the treatment of multiple sclerosis is to achieve the state of “no evidence of disease activity”, i.e. the NEDA index. In clinical practice, this leads to faster escalation of treatment or early implementation of highly active therapies as first-line. Current recommendations of ECTRIMS experts advised the use of more active disease-modifying therapies such as oral cladribine (CladT) in earlier stages of disease. The proven long-term effectiveness of CladT results from a properly selected patient profile. A full course of oral cladribine therapy does not require further treatment for at least 4 years in most patients. This makes it all the more important to identify markers that will predict a positive and long-term response to CladT treatment.
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References
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23. Rauma I, Viitala M, Kuusisto H et al. Finnish multiple sclerosis patients treated with cladribine tablets: a nationwide registry study. Mult Scler Relat Disord. 2022; 61: 103755.
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27. Möhn N, Skripuletz T, Sühs KW et al. Therapy with cladribine is efficient and safe in patients previously treated with natalizumab. Ther Adv Neurol Disord. 2019; 12.
28. Cleveland Clinic Mellen Center for Multiple Sclerosis Treatment and Research. Mellen center approaches: highly active multiple sclerosis. 216.444.8600.
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30. Lim ZW, Elwood E, Naveed H et al. Lymphopenia in treatment-naive relapsing multiple sclerosis: table. Neurol Neuroimmunol Neuroinflamm. 2016; 3: e275.
31. Morales FS, Koralnik IJ, Gautam S et al. Risk factors for lymphopenia in patients with relapsing–remitting multiple sclerosis treated with dimethyl fumarate. J Neurol. 2020; 267: 125-31.
2. Kapica-Topczewska K, Brola W, Fudala M et al. Prevalence of multiple sclerosis in Poland. Mult Scler Relat Disord. 2018; 21: 51-5.
3. Hauser SL, Cree BAC. Treatment of Multiple Sclerosis: A Review. Am J Med. 2020; 133(12): 1380-90.e2.
4. Pandit L. No Evidence of Disease Activity (NEDA) in Multiple Sclerosis – Shifting the Goal Posts. Ann Indian Acad Neurol. 2019; 22(3): 261-3.
5. Rammohan K, Coyle PK, Sylvester E et al. The development of cladribine tablets for the treatment of multiple sclerosis: a comprehensive review. Drugs. 2020; 80: 1901-28.
6. Merck (2022). Mavenclad 10 mg Tablets SmPC. (access: 12.2022).
7. Comi G, Cook S, Giovannoni G et al. Effect of cladribine tablets on lymphocyte reduction and repopulation dynamics in patients with relapsing multiple sclerosis. Mult Scler Relat Disord. 2019; 29: 168-74.
8. Giovannoni G, Soelberg Sorensen P, Cook S et al. Safety and efficacy of cladribine tablets in patients with relapsing-remitting multiple sclerosis: results from the randomized extension trial of the CLARITY study. Mult Scler. 2018; 24: 1594-604.
9. Giovannoni G, Comi G, Cook S et al. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. NEJM. 2010; 362: 416-26.
10. Giovannoni G, Cook S, Rammohan K et al. Sustained disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with cladribine tablets in the CLARITY study: a post-hoc and subgroup analysis. Lancet Neurol. 2011; 10: 329-37.
11. Leist T, Comi G, Cree B et al. Effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event (ORACLE MS): a phase 3 randomised trial. Lancet Neurol. 2014; 13: 257-67.
12. Montalban X, Leist TP, Cohen BA et al. Cladribine tablets added to IFN-b in active relapsing MS: the ONWARD study. Neurol Neuroimmunol Neuroinflamm. 2018; 5: e477.
13. Cook S, Leist T, Comi G et al. Safety of cladribine tablets in the treatment of patients with multiple sclerosis: an integrated analysis. Mult Scler Relat Disord. 2019; 29: 157-67.
14. Vermersch P, Galazka A, Dangond F et al. Efficacy of cladribine tablets in high disease activity patients with relapsing multiple sclerosis: post hoc analysis of subgroups with and without prior disease-modifying drug treatment. Curr Med Res Opin. 2021; 37: 459-64.
15. Giovannoni G, Leist T, Aydemir A; on behalf of the CLASSIC-MS Steering Committee. Long-term efficacy for patients receiving cladribine tablets in CLARITY/ CLARITY Extension: primary results from 9–15 years of follow-up in the CLASSIC-MS Study. ECTRIMS 13–15 October 2021.
16. Giovannoni G, Singer BA, Issard D et al. Durability of no evidence of disease activity-3 (NEDA-3) in patients receiving cladribine tablets: the CLARITY extension study. Mult Scler. 2022; 28: 1219-28.
17. Patti F, Visconti A, Capacchione A et al.; CLARINET-MS Study Group. Long-term effectiveness in patients previously treated with cladribine tablets: a real-world analysis of the Italian multiple sclerosis registry (CLARINET-MS). Ther Adv Neurol Disord. 2020; 13: 1756286420922685.
18. Dive D, Ernon C, Brouwers A. Cladribine: 14 years atrophy and clinical follow-up. Eur. Charcot Found. 2020. Virtual congress.
19. Meca-Lallana V, Domínguez JMG, Ruiz RL et al. Expert-Agreed Practical Recommendations on the Use of Cladribine. Neurol Ther. 2022; 11: 1475-88.
20. Zanetta C, Sangalli F, Guerrieri S et al. Efficacy/safety profile of cladribine in an italian real-life cohort of relapsing remitting multiple sclerosis patients. Eur J Neurol. 2021; 28: 325. EAN 2021 abstract (EPR-179).
21. Annovazzi P, Frau J, Margoni M et al. Two year relapse-free and NEDA status with Cladribine in a real-life population: a multicentre study. Mult Scler. 2021; 27: 693. ECTRIMS 2021 abstract (P842).
22. Petracca M, Ruggieri S, Barbuti E et al. Predictors of cladribine effectiveness in multiple sclerosis: a real-world, multicenter, two-year follow-up study. Eur J Neurol. 2022; 29: 787. EAN 2022 abstract (EPO-642).
23. Rauma I, Viitala M, Kuusisto H et al. Finnish multiple sclerosis patients treated with cladribine tablets: a nationwide registry study. Mult Scler Relat Disord. 2022; 61: 103755.
24. Zhong M, Van der Walt A, Hodgkinson S et al. Relapse during the washout period predicts time to relapse after switching to cladribine. Mult Scler. 2021; 27: 706-7.
25. Nygaard GO, Torgauten H, Skattebol L et al. Risk of fingolimod rebound after switching to cladribine or rituximab in multiple sclerosis. Mult Scler Relat Disord. 2022; 62: 103812..
26. Soelberg Sørensen PS, Centonze D, Giovannoni G et al. Expert opinion on the use of cladribine tablets in clinical practice. Ther Adv Neurol Disord. 2020; 13: 1-17.
27. Möhn N, Skripuletz T, Sühs KW et al. Therapy with cladribine is efficient and safe in patients previously treated with natalizumab. Ther Adv Neurol Disord. 2019; 12.
28. Cleveland Clinic Mellen Center for Multiple Sclerosis Treatment and Research. Mellen center approaches: highly active multiple sclerosis. 216.444.8600.
29. Zanghi A, Gallo A, Avolio C et al. Exit strategies in natalizumab-treated RRMS at high risk of progressive multifocal leukoencephalopathy: a multicentre comparison study. Neurotherapeutics. 2021; 18: 1166-74.
30. Lim ZW, Elwood E, Naveed H et al. Lymphopenia in treatment-naive relapsing multiple sclerosis: table. Neurol Neuroimmunol Neuroinflamm. 2016; 3: e275.
31. Morales FS, Koralnik IJ, Gautam S et al. Risk factors for lymphopenia in patients with relapsing–remitting multiple sclerosis treated with dimethyl fumarate. J Neurol. 2020; 267: 125-31.