First Guidelines for De-escalating and Discontinuing MS Therapies Released

A panel of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) has developed the first comprehensive guidelines for de-escalating and discontinuing disease-modifying therapies (DMTs) in individuals diagnosed with multiple sclerosis (MS). The guidelines, published in Brain, identify specific clinical scenarios where treatment reduction may be appropriate, driven primarily by changing benefit-risk ratios associated with aging and immunosenescence.

The recommendations were developed from a focused workshop organized by ECTRIMS in 2023, which brought together international MS experts to review the current evidence on DMT de-escalation strategies. The panel considered several clinical scenarios, including aging-related changes, pregnancy planning, pediatric-onset MS (POMS) patients transitioning to adulthood, and patients with comorbidities or treatment-related risks. The experts analyzed data from multiple observational studies and recent randomized controlled trials, including the DISCOMS (NCT03073603) and DOT-MS (NCT04260711) trials.

Key findings and recommendations include:

• Age (≥55 years) and the clinical and radiological stability of disease activity (5+ years) are the most important criteria for considering de-escalation. 
• Anti-CD20 therapies show the lowest rebound risk, making extended interval dosing a promising de-escalation strategy. 
• Sphingosine-1-phosphate receptor (S1PR) modulators and Tysabri (natalizumab; Biogen, Cambridge, MA) require careful transition planning due to high-reactivation risk. 
• For pregnancy planning, specific timelines were established for each DMT class.
• The framework emphasizes shared decision-making between patients and physicians and mandatory monitoring after de-escalation.

These guidelines address a growing clinical need as individuals diagnosed with MS live longer and accumulate treatment-related risks over time as well as experience age-related changes in their immune systems. 

Source: Androdias G, Lünemann JD, Maillart E, et al. De-escalating and discontinuing disease-modifying therapies in multiple sclerosis. Brain. 2025;148:1459–1478. https://doi.org/10.1093/brain/awae409.