A retrospective multicentre study (N=139) reports that a transition time <30 days when switching from natalizumab to an anti-CD20 agent is optimal for efficacy and safety (Bsteh et al. Eur J Neurol 2025;32:e16587). Mean age of patients at the time of switch was 38.8 years; median duration on natalizumab was 4.4 years.

The median time from last natalizumab infusion to first dose of anti-CD20 treatment was 58 days. Few patients relapsed (12.9%) in the one year following treatment switch. Two-thirds of the relapses occurred during the transition period. The relapse rate was 0% when the transition period was <30 days, 11.1% with a transition period of 30-44 days, and 16.1% for transitions >45 days. A transition period >45 days was associated with a 4.73-fold increased risk of relapse. There were no cases of progressive multifocal leukoencephalopathy (PML).

A number of previous studies have examined natalizumab switch strategies. An observational study reported a higher rate of no evidence of disease activity (NEDA) with a direct versus delayed switch to ocrelizumab (83% vs. 50%) in JC virus antibody-positive patients (van Lierop et al. Mult Scler J Exp Transl Clin 2021;7:20552173211013831). A caveat, however, was that two patients in the direct switch group were diagnosed with carry-over PML, demonstrating the importance of ruling out PML prior to the changeover.

A separate study found that switching from natalizumab to ocrelizumab was a better exit strategy than switching to fingolimod (Bigaut et al. J Neurol 2022;269:3295-3300). In the year after switching, the annualized relapse rate was significantly lower in the ocrelizumab versus fingolimod group (0.12 vs. 0.41). The cumulative probability of relapses at one year was 10.4% versus 31.5% , respectively (hazard ratio 3.4 favouring ocrelizumab).

A small pilot study (N=30) found that an alternative to switching to an anti-CD20 agent was use of extended-interval dosing of natalizumab (from q4wk to q8wk) (Santiago-Setien et al. Front Immunol 2023:14:1086028). The median transition period to ocrelizumab was six weeks. There were no significant differences between the two groups with respect to ARR or MRI activity at 96 weeks. However, a higher proportion of patients in the ocrelizumab group maintained NEDA status (94% vs. 69%).