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In JNNP, Konen et al provide real-world evidence that, in carefully selected stable patients with multiple sclerosis (MS), discontinuation of ocrelizumab after about 30 months was not associated with a statistically significant increase in inflammatory disease activity over a median follow-up of 28.5 months1, a relevant finding given that, although anti-CD20 therapies are highly effective in suppressing focal inflammatory activity, prolonged continuous B-cell depletion raises increasing concerns about hypogammaglobulinaemia, recurrent infections and impaired humoral vaccine responses.2 However, the CIs were wide, and disease activity showed a numerical increase beyond 24 months off treatment, arguing less for ‘safety’ than for cautious feasibility under structured surveillance.1 The next clinical question is therefore not only whether anti-CD20 therapy can be stopped, but how. Here, de-escalation may be more attractive than simple withdrawal in selected patients at higher infectious risk.