# Treatment-free remission in MS: long-term disease control with cladribine tablets

**Authors:** Heinz Wiendl, Ralf Gold, Refik Pul, Michael Ernst, Markus C. Kowarik, Juliane Klehmet, Ines Siglienti, Michael Hübschen, Torsten Wagner, Judith Knaup, Christoph Kleinschnitz

PMC · DOI: 10.1007/s00415-026-13753-w · Journal of Neurology · 2026-03-18

## TL;DR

Cladribine tablets may allow long-term remission in multiple sclerosis by enabling extended treatment-free periods.

## Contribution

The paper presents long-term real-world data showing cladribine's potential for treatment-free remission in RMS.

## Key findings

- Most patients remained without additional therapy beyond year 4, suggesting stable disease control.
- Retreatment with cladribine tablets was effective and tolerable in cases of mild recurring disease activity.
- Cladribine enables long-term therapeutic options by preserving immune system recovery.

## Abstract

Oral cladribine, a highly effective pulsed selective immune reconstitution therapy (SIRT) for relapsing multiple sclerosis (RMS) is characterised by extended treatment-free periods following brief exposure to medication. Since approval in 2017, long-term real-world data have become available which provide insight into the management of patients treated with cladribine tablets beyond year 4. Most patients remained without additional therapy, which may hint at stable disease control. However, the absence of further treatment must not necessarily be interpreted as absence of any disease activity, as MRI data are often incomplete in watch-and-wait cohorts. The observed long-term remission is likely linked to the unique mode of action, which involves rapid repopulation of lymphocytes with different dynamics amongst subsets and sustained reduction of memory B cells. The recovery of the immune system and lymphocytes preserves long-term therapeutic options with existing or upcoming drugs. In cases of mild recurring disease activity, retreatment with cladribine tablets has been shown to be effective and tolerable within the known safety profile. Unrestricted long-term management options associated with cladribine tablets include a switch to other DMTs in cases of insufficient disease control. Overall, cladribine tablets show potential of a paradigmatic shift in MS management that may enable treatment-free remission over 6 years as an achievable treatment goal in a substantial proportion of RMS patients.

## Linked entities

- **Chemicals:** cladribine (PubChem CID 20279)
- **Diseases:** multiple sclerosis (MONDO:0005301)

## Full-text entities

- **Genes:** CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, IFNB1 (interferon beta 1) [NCBI Gene 3456] {aka IFB, IFF, IFN-beta, IFNB}, NEFL (neurofilament light chain) [NCBI Gene 4747] {aka CMT1F, CMT2E, CMTDIG, NF-L, NF68, NFL}, GFAP (glial fibrillary acidic protein) [NCBI Gene 2670] {aka ALXDRD}, KRT20 (keratin 20) [NCBI Gene 54474] {aka CD20, CK-20, CK20, K20, KRT21}
- **Diseases:** herpes zoster (MESH:D006562), nausea (MESH:D009325), infection (MESH:D007239), headache (MESH:D006261), alopecia (MESH:D000505), cancer (MESH:D009369), MS (MESH:D009103), progressive multifocal leukoencephalopathy (MESH:D007968), liver toxicity (MESH:D056486), opportunistic infections (MESH:D009894), Lymphopenia (MESH:D008231), inflammatory disease (MESH:D007249), RMS (MESH:D020529)
- **Chemicals:** DMT (-), Cladribine (MESH:D017338)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12996015/full.md

## References

1 references — full list in the complete paper: https://tomesphere.com/paper/PMC12996015/full.md

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Source: https://tomesphere.com/paper/PMC12996015