Stopping DMT: when or if at all?

A hot topic session addressed the question of whether disease-modifying therapy (DMT) can be stopped at some point. In patients with relapsing-remitting MS (RRMS), older age (>55 years) and longer No Evidence of Disease Activity-3 (NEDA-3; >5 years) consistently predict a successful DMT discontinuation [1]. In progressive MS (PMS), one of the options worth considering may be a de-risking strategy, by switching onto safer immunomodulatory therapies [2].

Prof. Ilya Kister (NYU Grossman School of Medicine, NY, USA) explained during her presentation that most DMTs are approved for indefinite use, but it is unclear whether they should be used indefinitely and, if not, on which variables the decision to stop DMT should depend. Prof. Kister presented a review of over a dozen recent, retrospective, observational studies of DMT discontinuation in RRMS [1]. These studies have identified various variables that may help to predict low risk of relapse after discontinuing therapy: most notably older age, prolonged disease stability, lower disability rank, absence of MRI activity, and low neurofilament light chain (NfL). However, it is unknown whether stopping DMT impacts progression independent of relapse activity (PIRA), subclinical disease activity, and brain atrophy.

Studies with a required period of disease stability prior to stopping DMT showed RRMS patients <45 years of age were at high risk of disease activity after stopping DMT even following a period of disease quiescence. Patients with no relapses for >5 years did not appear to benefit from continuing an injectable DMT. Studies with a required age threshold at DMT stop showed that the risk of relapse after stopping injectable DMT was low, among older patients. Finally, studies that required neither age threshold nor stability showed that older age (>55 years) and longer NEDA-3 (>5 years) predicted a successful DMT stop. Combining these variables may help identify subgroups of RRMS patients with very low risk of disease reactivation after stopping DMT.

Prof. Gavin Giovannoni (Queen Mary University of London, UK) discussed stopping criteria for patients with progressive forms of MS [2]. The older the patient, the more likely they are to have progressive MS, and the less likely to have evident disease activity (EDA) on stopping DMT. It is unknown if this is related to age or to the biology of the disease. “What I do know is that –on a population level– if the patient has been free of disease activity for 4 years, this predicts continuing to be free of disease activity on stopping.” However, if patients had highly active MS when starting DMT (especially natalizumab or fingolimod), the disease tends to ‘reactivate’.

As patients with progressive MS are older and tend to have more comorbidities, the risk-benefit ratio changes. Factors such as immunosenescence, infection and cancer risk, vaccine responsiveness, and comorbidities, in particular cardiovascular risk, need to be weighed up when deciding to continue or stop DMT [3]. Prof Giovannoni believes there should be a focus on de-risking strategies: switching patients onto safer immunomodulatory therapies. Another option is to select an immune reconstitution therapy that is not associated with long-term immunosuppression in this phase of the disease.

1. Kister I. In relapsing MS. OP066, ECTRIMS 2021 Virtual Congress, 13–15 October.
2. Giovannoni G. In progressive MS. OP067, ECTRIMS 2021 Virtual Congress, 13–15 October.
3. Hartung HP, et al. Curr Opinion Neurol 2021; 34(4):598-603

 

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Posted on 9 December, 202125 March, 2024