Challenges of de-escalation versus discontinuation of highly effective DMTs in older MS patients

Neurologists may consider re-evaluating the benefit/risk ratio of high-efficacy therapy (HET) in older MS patients who have had stable disease for a long time. Several strategies can be adopted for de-escalation or discontinuation of HET, depending on the type or mode of action of the therapy in question.

Prof. Vincent Van Pesch (UCLouvain, Belgium) stated the main reasons to re-evaluate ongoing HET in ageing MS patients [1]:

• The prevalence of ageing MS patients is increasing.
• MS changes with increasing age, possibly affecting response to disease-modifying treatment (DMTs). There is a decrease in relapse rate (of 17% every 5 years), in occurrence of new lesions, and in relapse recovery.
• With ageing, the immune system gradually declines (immunosenescence) and chronic low-grade inflammation (‘inflammageing’) occurs. This may influence the safety of DMTs.
• The risk of infection associated with HET increases with age.
• The risk of neoplasms increases with age, especially in MS.
• There is a possible increase in autoreactive cell populations.

In older age, there is an increased risk of disability progression and of DMTs becoming less effective. This changes the risk/benefit ratio of MS treatments. Prof. Van Pesch said that various strategies can be adopted for de-escalation or discontinuation of HET. Discontinuing DMTs interfering with lymphocyte trafficking (S1P modulators, natalizumab) produces a risk of rebound or recurrence of inflammatory disease activity. Prof. Van Pesch suggested switching to a less potent DMT or reducing the frequency of administration or dosing. Selective immune reconstitution therapies (cladribine, alemtuzumab) might be an exit strategy allowing to discontinue treatment completely.

De-escalation or discontinuation of HET is a complex decision, to be made on a case-by-case basis, Prof. Van Pesch stressed. Especially in long-term stable elderly patients, a re-evaluation of the benefits and risks of the treatment should be considered, though at what age (>60–65 years?) is yet to be determined. Age, disease duration, disability accrual, recent disease activity, co-morbidities, and patient preferences are among the factors to be taken into account.

1. Van Pesch V. De-escalation or discontinuation of highly effective DMTs in the ageing MS patient. O177, MSMilan 2023, 11–13 October, Milan, Italy.

 

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Posted on 4 December 20234 December 2023