De-escalating and discontinuing disease-modifying therapies in multiple sclerosis - Report - MDSpire

De-escalating and discontinuing disease-modifying therapies in multiple sclerosis

  • By

  • Géraldine Androdias

  • Jan D Lünemann

  • Elisabeth Maillart

  • Maria Pia Amato

  • Bertrand Audoin

  • Arlette L Bruijstens

  • Gabriel Bsteh

  • Helmut Butzkueven

  • Olga Ciccarelli

  • Alvaro Cobo-Calvo

  • Tobias Derfuss

  • Franziska Di Pauli

  • Gilles Edan

  • Christian Enzinger

  • Ruth Geraldes

  • Cristina Granziera

  • Yael Hacohen

  • Hans-Peter Hartung

  • Sinéad Hynes

  • Matilde Inglese

  • Ludwig Kappos

  • Hanna Kuusisto

  • Annette Langer-Gould

  • Melinda Magyari

  • Romain Marignier

  • Xavier Montalban

  • Marcin P Mycko

  • Bardia Nourbakhsh

  • Jiwon Oh

  • Celia Oreja-Guevara

  • Fredrik Piehl

  • Luca Prosperini

  • Jaume Sastre-Garriga

  • Finn Sellebjerg

  • Krzysztof Selmaj

  • Aksel Siva

  • Emma Tallantyre

  • Vincent van Pesch

  • Sandra Vukusic

  • Bianca Weinstock-Guttman

  • Frauke Zipp

  • Mar Tintoré

  • Ellen Iacobaeus

  • Bruno Stankoff

  • December 21, 2024

  • 0 min

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Clinical Report: Strategies for De-escalating and Discontinuing DMTs in Multiple Sclerosis

Overview

Disease-modifying therapies (DMTs) have transformed multiple sclerosis (MS) management, with early initiation improving long-term outcomes. However, the optimal timing and approach for de-escalating or discontinuing DMTs remain unclear, particularly as patients age or enter specific clinical scenarios such as pregnancy.

Background

Over the past three decades, MS treatment has evolved from relapse reduction to aiming for complete inflammatory control through various DMTs, including platform therapies, high-efficacy therapies (HETs), and immune reconstitution therapies (IRTs). While continuous maintenance therapy is common, there is growing interest in de-escalation strategies to balance efficacy with safety, especially considering immunosenescence and inflammaging in aging patients. The 2023 ECTRIMS workshop reviewed current evidence and practical recommendations for de-escalation and discontinuation of DMTs.

Data Highlights

The article discusses the classification of DMTs into platform therapies (e.g., interferon-β, glatiramer acetate), high-efficacy therapies (e.g., anti-CD20 antibodies, natalizumab), and immune reconstitution therapies (e.g., cladribine, alemtuzumab). It highlights the impact of aging-related immune changes such as immunosenescence and inflammaging on treatment benefit-risk balance but does not provide specific numerical data.

Key Findings

  • Early initiation of DMTs after MS onset is linked to better long-term prognosis.
  • De-escalation involves switching to less potent therapies, dose reduction, or extending dosing intervals; discontinuation is considered part of de-escalation strategies.
  • Age-related immune changes (immunosenescence and inflammaging) alter the benefit-risk ratio, often reducing DMT effectiveness and increasing risks.
  • Immune reconstitution therapies may allow prolonged remission without continuous treatment, representing a unique de-escalation mechanism.
  • There is currently no consensus on standardized de-escalation or discontinuation protocols in MS management.
  • Special clinical situations such as pregnancy and pediatric-onset MS require tailored de-escalation approaches.

Clinical Implications

Clinicians should regularly reassess the benefit-risk profile of DMTs, especially in aging patients or those with stable disease, to consider de-escalation or discontinuation. Individualized treatment plans incorporating patient age, disease activity, and specific clinical contexts can optimize long-term safety and quality of life. Monitoring strategies and guidelines from expert consensus, such as those from ECTRIMS, can aid in decision-making.

Conclusion

De-escalation and discontinuation of DMTs in MS represent important but complex strategies requiring further evidence and consensus. Tailored approaches considering immunological aging and patient-specific factors are essential to optimize outcomes.

References

  1. ECTRIMS Workshop 2023 -- Reducing and Stopping Disease-Modifying Treatments in Multiple Sclerosis

Original Source(s)

De-escalating and discontinuing disease-modifying therapies in multiple sclerosis

  • by Géraldine Androdias, Jan D Lünemann, Elisabeth Maillart, Maria Pia Amato, Bertrand Audoin, Arlette L Bruijstens, Gabriel Bsteh, Helmut Butzkueven, Olga Ciccarelli, Alvaro Cobo-Calvo, Tobias Derfuss, Franziska Di Pauli, Gilles Edan, Christian Enzinger, Ruth Geraldes, Cristina Granziera, Yael Hacohen, Hans-Peter Hartung, Sinéad Hynes, Matilde Inglese, Ludwig Kappos, Hanna Kuusisto, Annette Langer-Gould, Melinda Magyari, Romain Marignier, Xavier Montalban, Marcin P Mycko, Bardia Nourbakhsh, Jiwon Oh, Celia Oreja-Guevara, Fredrik Piehl, Luca Prosperini, Jaume Sastre-Garriga, Finn Sellebjerg, Krzysztof Selmaj, Aksel Siva, Emma Tallantyre, Vincent van Pesch, Sandra Vukusic, Bianca Weinstock-Guttman, Frauke Zipp, Mar Tintoré, Ellen Iacobaeus, Bruno Stankoff

  • December 21, 2024

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