Abstract
Background: Discontinuation of cell-trafficking therapies (e.g., natalizumab, fingolimod) carries a risk of disease reactivation or rebound. Age-related immunosenescence may influence this risk, but evidence guiding treatment transitions in patients aged ⩾50 years remains limited.
Objective: To assess the comparative effectiveness of various exit strategies after discontinuation of cell-trafficking disease modifying therapy (DMT) in MS patients aged ⩾50 years of age, followed up in the MSBase, the Italian MS Register, and the Swiss MS Cohort.
Methods: Patients with ⩾3 visits, complete datasets, and ⩾6 months on cell-trafficking DMTs, with treatment modifications at age ⩾50, were categorized as: (A) switch to anti-CD20, (B) switch to cladribine, (C) de-escalation to lower-efficacy cell-trafficking agent, or (D) de-escalation to lower-efficacy non-cell-trafficking DMT. Each subgroup was matched to patients continuing their DMT and, separately, to those discontinuing treatment, using 11 covariates. Time to relapse was compared using Cox proportional hazards models.
Results: Of 138,379 patients, 22,454 were included. 2,057 underwent treatment-modifications at age ⩾50 (age: 57.2±5.6years; EDSS: 4.5 [3.0–6.0]). Switching to anti-CD20 (n=498 pairs) or cladribine (n=84) showed similar relapse-risk compared with continuation (HR 0.82 [0.50–1.35]; 3.89 [0.76–20.0]). Stopping treatment (n=478) increased relapse risk compared with switching to anti-CD20 (2.40 [1.48–3.90]), but not with de-escalation to lower-efficacy cell-trafficking (n=262, 0.71 [0.41– 1.20]) or non-cell-trafficking DMT (n=300, 0.52 [0.35–0.80]).
Conclusion: After 50th year of age, switching to anti-CD20 or cladribine after discontinuing a cell-trafficking agent is associated with a relapse risk similar to continued therapy. In contrast, de-escalation to lower-efficacy agents offers no apparent advantage over treatment cessation.