Abstract
Background: Discontinuation of cell-trafficking therapies (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 compare relapse risk after natalizumab/fingolimod discontinuation in MS patients ⩾50 years when switching to anti-CD20, cladribine, de-escalation, or stopping therapy.
Methods: The MSBase, Italian, and Swiss MS cohorts contributed patients with ⩾3 visits, complete data, and ⩾6 months on an anti-trafficking therapy. Treatment decisions after age ⩾50 were: switch to (A) anti-CD20, (B) cladribine, (C) lower-efficacy anti-trafficking therapy, or (D) low efficacy non-anti-trafficking therapy. Each subgroup was 1:1 propensity-matched using 11 covariates to continuers and, separately, discontinuers. Weighted Cox models compared time-to-first relapse in pairwise-censored groups.
Results: 22,454 patients met inclusion criteria, of whom 2,057 changed treatment at age ⩾50. Switching to anti-CD20 therapy/cladribine resulted in similar relapse risk compared with treatment continuation. De-escalation to a lower-efficacy anti-trafficking or non-cell trafficking DMT was associated with a higher relapse risk (HR 2.45[1.31–4.57], HR 3.97[2.39–6.60]). Stopping treatment increased relapse risk compared with switching to anti-CD20 (HR 2.40[1.48–3.90]), but not compared with treatment de-escalation.
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.