Recommendation of Polish clinical experts on practical aspects of using cladribine in tablets Experts recommendations
Article Sidebar
Published:
Dec 31, 2023
Keywords:
multiple sclerosis, cladribine in tablets, recommendations
Main Article Content
Abstract
Cladribine in tablets is available in Poland for the treatment of relapsing-remitting multiple sclerosis, both in the first and second line of treatment and for the rapidly evolving severe multiple sclerosis. In this study, a group of Polish experts, based on their own clinical experience and literature data, have formulated practical recommendations for practitioners regarding the use of cladribine in tablets. The issues discussed included the profile of the patient in whom the drug can be used, factors predicting the effectiveness of treatment, changing treatment from other disease-modifying therapies to cladribine and vice versa, the safety profile of the drug, the effectiveness of vaccinations during treatment, the interaction of cladribine with other preparations, diagnostics before starting the drug, monitoring treatment and planning pregnancy.
Article Details
Issue
Section
Articles
Copyright © by Medical Education. All rights reserved.
References
1. Program lekowy B.29 Leczenie chorych na stwardnienie rozsiane (access: 27.11.2023).
2. Kułakowska A, Mirowska-Guzel D, Kalinowska A et al. Leczenie modyfikujące przebieg stwardnienia rozsianego. Rekomendacje Sekcji Stwardnienia Rozsianego i Neuroimmunologii Polskiego Towarzystwa Neurologicznego. Pol Przegl Neurol. 2023; 19(3): 163-89.
3. Charakterystyka produktu leczniczego Mavenclad (access: 27.11.2023).
4. Annovazzi P, Prosperini L, Capuano R et al. Relapse-free and NEDA status with Cladribine in a real life population: a multicentre study. ECTRIMS, 13–15 Oct. Poster Present P842. 2021.
5. Petracca M, Ruggieri S, Barbuti E et al. Predictors of Cladribine Effectiveness and Safety in Multiple Sclerosis: A Real-World, Multicenter, 2-Year Follow-Up Study. Neurol Ther. 2022; 11(3): 1193-208.
6. Meca-Lallana V, García Domínguez JM, López Ruiz R et al. Expert-Agreed Practical Recommendations on the Use of Cladribine. Neurol Ther. 2022; 11(4): 1475-88.
7. Montalban X. Update to the ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis. ECTRIMS, 13–15 Oct. Oral Present O184. 2021.
8. 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: 175628642093501.
9. Barry B, Erwin AA, Stevens J et al. Fingolimod Rebound: A Review of the Clinical Experience and Management Considerations. Neurol Ther. 2019; 8(2): 241-50.
10. Clerico M, Artusi C, Liberto A et al. Natalizumab in Multiple Sclerosis: Long-Term Management. Int J Mol Sci. 2017; 18(5): 940.
11. 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: 175628641988759.
12. Giovannoni G, Marta M, Davis A et al. Switching patients at high risk of PML from natalizumab to another disease-modifying therapy. Pract Neurol. 2016; 16(5): 389-93.
13. Adamec I, Jovanović I, Krbot Skorić M et al. Double immune reconstitution therapy: Cladribine after alemtuzumab in the treatment of multiple sclerosis. Eur J Neurol. 2022; 29(3): 901-4.
14. Stępień A, Pogoda-Wesołowska A, Tokarz-Kupczyk E et al. Cladribine tablets for highly active relapsing-remitting multiple sclerosis in Poland: a real-world, multi-centre, retrospective, cohort study during the COVID-19 pandemic. Neurol Neurochir Pol. 2023; 57(4): 371-8.
15. Celius EG. Normal antibody response after COVID-19 during treatment with cladribine. Mult Scler Relat Disord. 2020; 46: 102476.
16. Dersch R, Wehrum T, Fähndrich S et al. COVID-19 pneumonia in a multiple sclerosis patient with severe lymphopenia due to recent cladribine treatment. Mult Scler. 2020; 26(10): 1264-6.
17. Oreja-Guevara C, Meca-Lallana V, Brieva L et al. COVID-10 in cladribine treated patients with multiple sclerosis. ECTRIMS-ACTRIMS. 11-13 Sept. Poster Present LB1165. 2020.
18. Jack D, Nolting A, Galazka A. Favorable outcomes after COVID-19 infection in multiple sclerosis patients treated with cladribine tablets. Mult Scler Relat Disord. 2020; 46: 102469.
19. Pawłowska M, Flisiak R, Gil L et al. Profilaktyka reaktywacji zakażeń HBV – rekomendacje grupy roboczej profilaktyki reaktywacji HBV. Acta Haematol Pol. 2019; 50(4): 192-8.
20. Brownlee WJ, Wolf C, Hartung HP et al. Use of follow-on disease-modifying treatments for multiple sclerosis: Consensus recommendations. Mult Scler. 2022; 28(14): 2177-89.
21. Terranova N, Hicking C, Dangond F et al. Effects of Postponing Treatment in the Second Year of Cladribine Administration: Clinical Trial Simulation Analysis of Absolute Lymphocyte Counts and Relapse Rate in Patients with Relapsing-Remitting Multiple Sclerosis. Clin Pharmacokinet. 2019; 58(3): 325-33.
22. Otero-Romero S, Lebrun-Frénay C, Reyes S et al. ECTRIMS/EAN consensus on vaccination in people with multiple sclerosis: Improving immunization strategies in the era of highly active immunotherapeutic drugs. Mult Scler. 2023; 29(8): 904-25.
23. Coyle PK, Gocke A, Vignos M et al. Vaccine Considerations for Multiple Sclerosis in the COVID-19 Era. Adv Ther. 2021; 38(7): 3550-88.
24. Otero-Romero S, Rodríguez-García J, Vilella A et al. Recomendaciones para la vacunación en pacientes con esclerosis múltiple candidatos a terapias inmunosupresoras: documento de consenso español. Neurología. 2021; 36(1): 50-60.
25. Gold R, Fätkenheuer G, Hartung HP et al. Vaccination in multiple sclerosis patients treated with highly effective disease-modifying drugs: an overview with consideration of cladribine tablets. Ther Adv Neurol Disord. 2021; 14: 175628642110195.
26. Schmierer K, Wiendl H, Oreja-Guevara C et al. Varicella zoster virus and influenza vaccine antibody titres in patients from MAGNIFY-MS who were treated with cladribine tablets for highly active relapsing multiple sclerosis. Mult Scler J. 2022; 28(13): 2151-3.
27. Grothe C, Steffen F, Bittner S. Humoral immune response and lymphocyte levels after complete vaccination against COVID-19 in a cohort of multiple sclerosis patients treated with cladribine tablets. J Cent Nerv Syst Dis. 2021; 13:117957352110601.
28. Baker D, Herrod SS, Alvarez-Gonzalez C et al. Both cladribine and alemtuzumab may effect MS via B-cell depletion. Neurol Neuroimmunol Neuroinflamm. 2017; 4(4): e360.
29. AlJumah M, Alkhawajah MM, Qureshi S et al. Cladribine Tablets and Relapsing–Remitting Multiple Sclerosis: A Pragmatic, Narrative Review of What Physicians Need to Know. Neurol Ther. 2020; 9(1): 11-23.
30. Sorensen PS, Dangond F, Hicking Ch et al. Long-Term Lymphocyte Counts in Patients with RRMS Treated with Cladribine Tablets 3.5 Mg/Kg: Total Lymphocytes, B-, and T-Cell Subsets. ACTRIMS. 1-3 Feb. Poster Present P084. 2018.
31. Wiendl H, Schmierer K, Hodgkinson S et al. Specific Patterns of Immune Cell Dynamics May Explain the Early Onset and Prolonged Efficacy of Cladribine Tablets. Neurol Neuroimmunol Neuroinflamm. 2023; 10(1).
32. Giovannoni G, Comi G, Cook S et al. A Placebo-Controlled Trial of Oral Cladribine for Relapsing Multiple Sclerosis. N Engl J Med. 2010; 362(5): 416-26.
33. 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.
34. Dolk H, Loane M, Garne E. The Prevalence of Congenital Anomalies in Europe. Adv Exp Med Biol. 2010; 686: 349-64.
35. EUROCAT Datenbank (access: 25.10.2021).
36. Ziemssen T, Posevitz-Fejar A, Wagner T et al. Treatment emergent adverse events experienced early and transiently in the treatment course with cladribine tablets: data from the CLEVER real-world study. 26-28 Oct. ECTRIMS. Poster Present P772. 2022.
37. Galazka A, Nolting A, Cook S et al. An analysis of malignancy risk in the clinical development programme of cladribine tablets in patients with relapsing multiple sclerosis. 16-19 June. EAN. ePoster Present EPO1083. 2018.
38. Clavelou P, Castelnovo G, Pourcher V et al. Expert Narrative Review of the Safety of Cladribine Tablets for the Management of Relapsing Multiple Sclerosis. Neurol Ther. 2023; 12(5): 1457-76.
39. Hermann R, Karlsson MO, Novakovic AM et al. The Clinical Pharmacology of Cladribine Tablets for the Treatment of Relapsing Multiple Sclerosis. Clin Pharmacokinet. 2019; 58(3): 283-97.
40. Dost-Kovalsky K, Thiel S, Ciplea A et al. Cladribine and pregnancy in women with multiple sclerosis – a case series from Germany. 26-28 Oct. ECTRIMS. Poster Present P287. 2022.
41. MS und Kinderwunsch. Register DMSKW (access: 30.11.2023).
42. Hellwig K, Tilson H, Seebeck J et al. Pregnancy and Infant Outcomes from an Ongoing Worldwide Surveillance Program of Cladribine Tablets: 5-year Pharmacovigilance Results from MAPLE-MS. 23-25 Feb. ACTRIMS. Poster Present P482. 2023.
43. Datta P, Hale TW, Thiel S et al. Low transfer of cladribine into human milk. Mult Scler. 2023; 29(10): 1346-7.
2. Kułakowska A, Mirowska-Guzel D, Kalinowska A et al. Leczenie modyfikujące przebieg stwardnienia rozsianego. Rekomendacje Sekcji Stwardnienia Rozsianego i Neuroimmunologii Polskiego Towarzystwa Neurologicznego. Pol Przegl Neurol. 2023; 19(3): 163-89.
3. Charakterystyka produktu leczniczego Mavenclad (access: 27.11.2023).
4. Annovazzi P, Prosperini L, Capuano R et al. Relapse-free and NEDA status with Cladribine in a real life population: a multicentre study. ECTRIMS, 13–15 Oct. Poster Present P842. 2021.
5. Petracca M, Ruggieri S, Barbuti E et al. Predictors of Cladribine Effectiveness and Safety in Multiple Sclerosis: A Real-World, Multicenter, 2-Year Follow-Up Study. Neurol Ther. 2022; 11(3): 1193-208.
6. Meca-Lallana V, García Domínguez JM, López Ruiz R et al. Expert-Agreed Practical Recommendations on the Use of Cladribine. Neurol Ther. 2022; 11(4): 1475-88.
7. Montalban X. Update to the ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis. ECTRIMS, 13–15 Oct. Oral Present O184. 2021.
8. 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: 175628642093501.
9. Barry B, Erwin AA, Stevens J et al. Fingolimod Rebound: A Review of the Clinical Experience and Management Considerations. Neurol Ther. 2019; 8(2): 241-50.
10. Clerico M, Artusi C, Liberto A et al. Natalizumab in Multiple Sclerosis: Long-Term Management. Int J Mol Sci. 2017; 18(5): 940.
11. 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: 175628641988759.
12. Giovannoni G, Marta M, Davis A et al. Switching patients at high risk of PML from natalizumab to another disease-modifying therapy. Pract Neurol. 2016; 16(5): 389-93.
13. Adamec I, Jovanović I, Krbot Skorić M et al. Double immune reconstitution therapy: Cladribine after alemtuzumab in the treatment of multiple sclerosis. Eur J Neurol. 2022; 29(3): 901-4.
14. Stępień A, Pogoda-Wesołowska A, Tokarz-Kupczyk E et al. Cladribine tablets for highly active relapsing-remitting multiple sclerosis in Poland: a real-world, multi-centre, retrospective, cohort study during the COVID-19 pandemic. Neurol Neurochir Pol. 2023; 57(4): 371-8.
15. Celius EG. Normal antibody response after COVID-19 during treatment with cladribine. Mult Scler Relat Disord. 2020; 46: 102476.
16. Dersch R, Wehrum T, Fähndrich S et al. COVID-19 pneumonia in a multiple sclerosis patient with severe lymphopenia due to recent cladribine treatment. Mult Scler. 2020; 26(10): 1264-6.
17. Oreja-Guevara C, Meca-Lallana V, Brieva L et al. COVID-10 in cladribine treated patients with multiple sclerosis. ECTRIMS-ACTRIMS. 11-13 Sept. Poster Present LB1165. 2020.
18. Jack D, Nolting A, Galazka A. Favorable outcomes after COVID-19 infection in multiple sclerosis patients treated with cladribine tablets. Mult Scler Relat Disord. 2020; 46: 102469.
19. Pawłowska M, Flisiak R, Gil L et al. Profilaktyka reaktywacji zakażeń HBV – rekomendacje grupy roboczej profilaktyki reaktywacji HBV. Acta Haematol Pol. 2019; 50(4): 192-8.
20. Brownlee WJ, Wolf C, Hartung HP et al. Use of follow-on disease-modifying treatments for multiple sclerosis: Consensus recommendations. Mult Scler. 2022; 28(14): 2177-89.
21. Terranova N, Hicking C, Dangond F et al. Effects of Postponing Treatment in the Second Year of Cladribine Administration: Clinical Trial Simulation Analysis of Absolute Lymphocyte Counts and Relapse Rate in Patients with Relapsing-Remitting Multiple Sclerosis. Clin Pharmacokinet. 2019; 58(3): 325-33.
22. Otero-Romero S, Lebrun-Frénay C, Reyes S et al. ECTRIMS/EAN consensus on vaccination in people with multiple sclerosis: Improving immunization strategies in the era of highly active immunotherapeutic drugs. Mult Scler. 2023; 29(8): 904-25.
23. Coyle PK, Gocke A, Vignos M et al. Vaccine Considerations for Multiple Sclerosis in the COVID-19 Era. Adv Ther. 2021; 38(7): 3550-88.
24. Otero-Romero S, Rodríguez-García J, Vilella A et al. Recomendaciones para la vacunación en pacientes con esclerosis múltiple candidatos a terapias inmunosupresoras: documento de consenso español. Neurología. 2021; 36(1): 50-60.
25. Gold R, Fätkenheuer G, Hartung HP et al. Vaccination in multiple sclerosis patients treated with highly effective disease-modifying drugs: an overview with consideration of cladribine tablets. Ther Adv Neurol Disord. 2021; 14: 175628642110195.
26. Schmierer K, Wiendl H, Oreja-Guevara C et al. Varicella zoster virus and influenza vaccine antibody titres in patients from MAGNIFY-MS who were treated with cladribine tablets for highly active relapsing multiple sclerosis. Mult Scler J. 2022; 28(13): 2151-3.
27. Grothe C, Steffen F, Bittner S. Humoral immune response and lymphocyte levels after complete vaccination against COVID-19 in a cohort of multiple sclerosis patients treated with cladribine tablets. J Cent Nerv Syst Dis. 2021; 13:117957352110601.
28. Baker D, Herrod SS, Alvarez-Gonzalez C et al. Both cladribine and alemtuzumab may effect MS via B-cell depletion. Neurol Neuroimmunol Neuroinflamm. 2017; 4(4): e360.
29. AlJumah M, Alkhawajah MM, Qureshi S et al. Cladribine Tablets and Relapsing–Remitting Multiple Sclerosis: A Pragmatic, Narrative Review of What Physicians Need to Know. Neurol Ther. 2020; 9(1): 11-23.
30. Sorensen PS, Dangond F, Hicking Ch et al. Long-Term Lymphocyte Counts in Patients with RRMS Treated with Cladribine Tablets 3.5 Mg/Kg: Total Lymphocytes, B-, and T-Cell Subsets. ACTRIMS. 1-3 Feb. Poster Present P084. 2018.
31. Wiendl H, Schmierer K, Hodgkinson S et al. Specific Patterns of Immune Cell Dynamics May Explain the Early Onset and Prolonged Efficacy of Cladribine Tablets. Neurol Neuroimmunol Neuroinflamm. 2023; 10(1).
32. Giovannoni G, Comi G, Cook S et al. A Placebo-Controlled Trial of Oral Cladribine for Relapsing Multiple Sclerosis. N Engl J Med. 2010; 362(5): 416-26.
33. 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.
34. Dolk H, Loane M, Garne E. The Prevalence of Congenital Anomalies in Europe. Adv Exp Med Biol. 2010; 686: 349-64.
35. EUROCAT Datenbank (access: 25.10.2021).
36. Ziemssen T, Posevitz-Fejar A, Wagner T et al. Treatment emergent adverse events experienced early and transiently in the treatment course with cladribine tablets: data from the CLEVER real-world study. 26-28 Oct. ECTRIMS. Poster Present P772. 2022.
37. Galazka A, Nolting A, Cook S et al. An analysis of malignancy risk in the clinical development programme of cladribine tablets in patients with relapsing multiple sclerosis. 16-19 June. EAN. ePoster Present EPO1083. 2018.
38. Clavelou P, Castelnovo G, Pourcher V et al. Expert Narrative Review of the Safety of Cladribine Tablets for the Management of Relapsing Multiple Sclerosis. Neurol Ther. 2023; 12(5): 1457-76.
39. Hermann R, Karlsson MO, Novakovic AM et al. The Clinical Pharmacology of Cladribine Tablets for the Treatment of Relapsing Multiple Sclerosis. Clin Pharmacokinet. 2019; 58(3): 283-97.
40. Dost-Kovalsky K, Thiel S, Ciplea A et al. Cladribine and pregnancy in women with multiple sclerosis – a case series from Germany. 26-28 Oct. ECTRIMS. Poster Present P287. 2022.
41. MS und Kinderwunsch. Register DMSKW (access: 30.11.2023).
42. Hellwig K, Tilson H, Seebeck J et al. Pregnancy and Infant Outcomes from an Ongoing Worldwide Surveillance Program of Cladribine Tablets: 5-year Pharmacovigilance Results from MAPLE-MS. 23-25 Feb. ACTRIMS. Poster Present P482. 2023.
43. Datta P, Hale TW, Thiel S et al. Low transfer of cladribine into human milk. Mult Scler. 2023; 29(10): 1346-7.