Disease-Modifying Therapy (DMT) Switch in Highly Active Multiple Sclerosis: A Case Report

Penulis

  • Rocksy Fransisca V Situmeang Department of Neurology, Siloam Hospitals Lippo Village/ Faculty of Medicine, Pelita Harapan University, Tangerang, Banten,
  • Nadia Gabriella Faculty of Medicine, Pelita Harapan University, Tangerang, Banten

DOI:

https://doi.org/10.56951/jx5d6764

Kata Kunci:

cladribine, disease-modifying therapy, highly active multiple sclerosis, multiple sclerosis, relapsing-remitting MS

Abstrak

Background: Highly active multiple sclerosis (HAMS) is a severe phenotype of multiple sclerosis (MS), accounting for 10% of all relapsing-remitting MS (RRMS) cases, characterized by rapid clinical decline and disease progression despite treatment with disease-modifying therapy (DMT). It is associated with high morbidity and mortality rates, thus requiring different therapeutic approaches. We report a case of DMT switch in a 30-year-old female with HAMS.

Case: A 30-year-old female presented with a 3-month history of numbness and tingling on her fingers, back, and lower extremities. Examination revealed hyperreflexia and positive Hoffman-Tromner sign. Brain magnetic resonance imaging (MRI) revealed multiple demyelinating lesions suggestive of MS, including Dawson’s fingers. She was diagnosed with MS and initially treated with subcutaneous (SC) interferon beta-1a (IFNβ-1a) 22 mcg, three times weekly. As the patient continued to experience relapses and develop new lesions on biannual repetition of scans, she was diagnosed with RRMS. Four years after the initial diagnosis, her relapses became more frequent with incomplete recovery in between, suggestive of HAMS. Therapy was subsequently switched from IFNβ-1a to cladribine.

Conclusion: Two approaches in the treatment of MS are the escalation and induction therapy. To date, no standardized treatment protocols for HAMS have been established. Patients with HAMS are candidates for the induction approach due to the narrow window of opportunity for treatment and the risk of early disease progression. Despite the risk of developing adverse reactions from being on potent immunosuppressive drugs, the imminent neurological disability that comes with HAMS outweighs this risk. The use of immune-reconstitution DMTs helps to achieve no evidence of disease activity (NEDA). Cladribine has shown promising outcomes in the treatment of HAMS and is frequently used for induction therapy. 

Referensi

1. Marangi A, Federle L, Scotto-Opipari R, Stenta G, Perini F, Zuliani L. Early switch from cladribine to alemtuzumab in highly-active relapsing-remitting multiple sclerosis: a case report. Neuroimmunology Reports. 2022;2:100095.

2. Kalinowska-Łyszczarz A, Guo Y, Lucchinetti CF. Update on pathology of central nervous system inflammatory demyelinating diseases. Neurologia i Neurochirurgia Polska. 2022;56(3):201–9.

3. Ascherio A. Environmental factors in multiple sclerosis. Expert Review of Neurotherapeutics. 2013;13:3–9.

4. Iacobaeus E, Arrambide G, Amato MP, Derfuss T, Vukusic S, Hemmer B, et al. Aggressive multiple sclerosis (1): towards a definition of the phenotype. Multiple Sclerosis Journal. 2020;26:1031–44.

5. Díaz C, Zarco LA, Rivera DM. Highly active multiple sclerosis: an update. Multiple Sclerosis and Related Disorders. 2019;30:215–24.

6. Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. The Lancet Neurology. 2018;17:162–73.

7. De Stefano N, Sormani MP, Giovannoni G, Rammohan K, Leist T, Coyle PK, et al. Analysis of frequency and severity of relapses in multiple sclerosis patients treated with cladribine tablets or placebo: the Clarity and Clarity extension studies. Multiple Sclerosis Journal. 2021;28:111–20.

8. Koch-Henriksen N, Thygesen LC, Sørensen PS, Magyari M. Worsening of disability caused by relapses in multiple sclerosis: a different approach. Mult Scler Relat Disord. 2019;32:1–8.

9. Lublin FD, Baier M, Cutter G. Effect of relapses on development of residual deficit in multiple sclerosis. Neurology. 2003;61:1528–32.

10. Oleen-Burkey M, Castelli-Haley J, Lage MJ, Johnson KP. Burden of a multiple sclerosis relapse. Patient. 2012;5:57–69.

11. Filipi M, Jack S. Interferons in the treatment of multiple sclerosis. International Journal of MS Care. 2019;22:165–72.

12. Menzin J, Caon C, Nichols C, White LA, Friedman M, Pill MW. Narrative review of the literature on adherence to disease-modifying therapies among patients with multiple sclerosis. Journal of Managed Care Pharmacy. 2013;19(1 Suppl A):S24–40.

13. Hu X, Shang S, Nestorov I, Hasan J, Seddighzadeh A, Dawson K, et al. Compare: pharmacokinetic profiles of subcutaneous peginterferon beta-1a and subcutaneous interferon beta-1a over 2 weeks in healthy subjects. British Journal of Clinical Pharmacology. 2016;82:380–8.

14. Rieckmann P. Concepts of induction and escalation therapy in multiple sclerosis. Journal of the Neurological Sciences. 2009:277 Suppl 1:S42–5.

15. Comi G. Induction vs. escalating therapy in multiple sclerosis: Practical implications. Neurological Sciences. 2008;29:253–5.

16. Edan G, Le Page E. Induction therapy for patients with multiple sclerosis: why? when? how? CNS Drugs. 2013;27:403–9.

17. Manouchehri N, Shirani A, Salinas VH, Tardo L, Hussain RZ, Pitt D, et al. Clinical trials in multiple sclerosis: past, present, and future. Neurologia i Neurochirurgia Polska. 2022;56:228–35.

18. Giovannoni G, Soelberg Sorensen P, Cook S, Rammohan K, Rieckmann P, Comi G, 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. Multiple Sclerosis Journal. 2017;24:1594–604.

19. Rauma I, Viitala M, Kuusisto H, Atula S, Sipilä JO, Ryytty M, et al. Finnish multiple sclerosis patients treated with cladribine tablets: a nationwide registry study. Multiple Sclerosis and Related Disorder. 2022;61:103755.

20. Comi G, Cook S, Giovannoni G, Rieckmann P, Sørensen PS, Vermersch P, et al. Effect of cladribine tablets on lymphocyte reduction and repopulation dynamics in patients with relapsing multiple sclerosis. Multiple Sclerosis and Related Disorder. 2019;29:168–74.

21. Baker D, Herrod SS, Alvarez-Gonzalez C, Zalewski L, Albor C, Schmierer K. Both cladribine and alemtuzumab may affect MS via B-cell depletion. Neurology Neuroimmunology and Neuroinflammation. 2017;4(4):e360.

22. Stępień A, Pogoda-Wesołowska A, Tokarz-Kupczyk E, Słowik A, Puz P, Adamczyk-Sowa M, et al. Cladribine tablets for highly active relapsing-remitting multiple sclerosis in Poland: a real-world, multicentre, retrospective cohort study during the COVID-19 pandemic. Neurologia i Neurochirurgia Polska. 2023;57(4):371–8.

Diterbitkan

02-04-2025

Unduhan

Cara Mengutip

[1]
Disease-Modifying Therapy (DMT) Switch in Highly Active Multiple Sclerosis: A Case Report. MEDICINUS 2025;38:21-8. https://doi.org/10.56951/jx5d6764.