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. 2025 Apr:96:106339.
doi: 10.1016/j.msard.2025.106339. Epub 2025 Feb 22.

Impact of oral Cladribine on paramagnetic rim lesions of Multiple Sclerosis patients

Mariano Marrodan  1 , Paulina Yañez  2 , Ismael L Calandri  3 , María Agustina Piedrabuena  4 , María A Zárate  5 , María C Ysrraelit  6 , Marcela Fiol  7 , Jorge Correale  8
Affiliations

Impact of oral Cladribine on paramagnetic rim lesions of Multiple Sclerosis patients

Mariano Marrodan et al. Mult Scler Relat Disord. 2025 Apr.

Abstract

Background: Paramagnetic rim lesions (PRLs), marked by chronic inflammation and iron-loaded microglia, are linked to severe disease progression in multiple sclerosis (MS). The impact of cladribine, an immune reconstitution therapy, on PRLs remains underexplored.

Objective: To evaluate the effect of cladribine tablets on PRLs in relapsing-remitting MS (RRMS) patients and explore the association between PRLs dynamics and brain atrophy.

Methods: We conducted a retrospective analysis of 52 RRMS patients treated with cladribine in Buenos Aires between 2018 and 2021. Brain MRIs were analyzed at baseline, 12, and 24 months post-treatment, focusing on PRLs count and brain volume measurements. Statistical analyses included Wilcoxon tests, Poisson mixed models, and linear mixed models.

Results: The cohort included 52 patients (32 women) with a median age of 36 years (range 21-66 years). PRLs were present in 61.5% of patients at baseline. Cladribine treatment significantly reduced PRLs count (IRR=0.68, 95% CI [0.49, 0.95], p=0.02), independent of prior treatment or disease activity. While no significant relationship was found between PRLs changes and overall brain atrophy, a significant interaction between PRLs dynamics and atrophy in the right thalamus was observed (p<0.05).

Conclusion: Cladribine tablets are associated with a reduction in PRLs in RRMS patients, potentially influencing regional brain atrophy over time.

Keywords: Cladribine; Multiple Sclerosis; Paramagnetic rim lesions.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mariano Marrodan has received fees for educational presentations and/or conference attendance from Merck-Serono Argentina, Biogen-Idec Argentina, Novartis Argentina, Gador, Astra-Zeneca, Raffo and Roche Argentina. Paulina Yañez has nothing to disclose. Ismael L. Calandri has nothing to disclose. Maria A. Zarate has nothing to disclose. Maria A. Piedrabuena has received fees for educational presentations from Novartis Argentina, Merck and Raffo. Maria C. Ysrraelit has received reimbursement for developing educational presentations, attendance to advisory boards and travel/accommodations stipends from Merck-Serono Argentina, Biogen, Genzyme Argentina, Bayer Inc, Novartis Argentina, TEVA and Roche Argentina. Marcela Fiol has received fees for educational presentations and/or conference attendance from Merck-Serono Argentina,Biogen-Idec Argentina, Genzyme Argentina, Bayer Inc, Novartis Argentina, Roche Argentina and TEVA. Jorge Correale has received financial compensation for academic presentations, and attended advisory boards from: Biogen, Merck, Novartis, Roche, Bayer, Sanofi-Genzyme, Gador, Raffo, Bristol Myers Squibb, and Janssen.

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