Switching from natalizumab to antiCD20 monoclonal antibodies: Short transition interval is associated with improved outcome.

Objective
To investigate the impact of transition interval length when switching from natalizumab (NTZ) to anti-CD20 monoclonal antibodies (antiCD20) on recurrent disease activity and safety in relapsing multiple sclerosis (RMS).
Methods
Aggregating data from 8 MS centres in Austria, Switzerland, and Germany, we included RMS patients who (i) continuously received NTZ for ≥3 months, (ii) were switched to antiCD20, and (iii) had ≥12 months follow-up after switch. The primary endpoint was occurrence of relapse after switch, secondary endpoints included severe infections (CTCAE grade ≥3).
Results
Overall, 139 RMS patients were included (70.5% females, mean age at switch 38.8 years [SD 9.7], mean disease duration at switch 11.3 years [SD 6.2], median duration on NTZ 4.4 years [range: 0.3-16.4], median transition interval 58 days [0-180]). Relapse occurred in 18 patients (12.9%) after NTZ discontinuation. Of those, 11 (61.1%) patients relapsed during the transition interval. No patient with a transition interval below 30 days experienced a relapse, compared to 11.1% and 16.1% with transition intervals of 30-44 days and ≥ 45 days, respectively. In multivariable Cox regression, a transition interval ≥ 45 days predicted a 4.73-fold increased risk of relapse. Over approximately 4 years of follow-up, six severe infections were reported without any noticeable effect of transition interval length. No PML occurred.
Conclusions
Switching from NTZ to antiCD20 is generally both effective and safe. Keeping the transition interval below 30 days provides the optimal balance between preventing recurrent disease activity and ensuring safety.