Impact of Switching from Natalizumab to a Moderate versus High Efficacy DMT in Clinical Practice at 24-Month Follow-Up
Carrie Hersh1, Haleigh Harris1, Devon Conway2, Le Hua1
1Lou Ruvo Center for Brain Health, 2Mellen Center for MS Treatment and Research, Cleveland Clinic
To assess the impact of switching from natalizumab (NTZ) to a moderate (Mod) disease modifying therapy (DMT) vs. high efficacy therapy (HET) in multiple sclerosis (MS) patients at 24-month follow-up.
Long-term use of NTZ is limited by potential safety risks that can be reduced by switching to an alternative therapy. However, NTZ discontinuation may trigger rebound disease, resulting in disability. Our previous study showed patients switching to Mod DMT vs. HET were at higher risk of early MRI disease activity by 6 months.
Patients discontinuing NTZ at two MS centers (n=556) who switched to Mod DMT (n=270) vs. HET (n=130) were assessed using propensity score (PS) weighting. Outcomes included ARR ratio and proportions with new T2 and/or gadolinium enhancing (GdE) lesions, absence of disease activity (a composite measure of no relapses and/or MRI activity), and 20% worsening of the timed twenty-five foot walk (T25FW) and 9-hole peg test (9-HPT). All outcomes were reported as Mod DMT vs. HET. 
In our cohort, 48.6% switched to Mod DMT (dimethyl fumarate, n=130; fingolimod, n=140) vs. 23.4% who switched to HET (ocrelizumab, n=106; rituximab, n=17; alemtuzumab, n=7). Reasons for NTZ discontinuation included PML risk (54.9%), breakthrough disease (15.3%), and adverse effects (17.3%). At 24-month follow-up, there were no differences in ARR [OR=1.44, 95% CI (0.69-1.59), p=0.334)]. However, patients switching to Mod DMT had higher proportions with new T2 lesions [OR=2.15, 95% CI (1.18-3.01), p=0.011], new GdE lesions [OR=1.99, 95% CI (1.12-2.73), p=0.022], and 20% worsening of the T25FW [OR=1.83, 95% CI (1.06-3.02), p=0.043] and 9-HPT [OR=1.81, 95% CI (1.05-3.56), p=0.044]; and lower proportion with absence of disease activity [OR=0.41, 95% CI (0.21-0.71), p=0.004].
At 24 months, NTZ switchers to Mod DMT had lower cumulative probability of no disease activity by 24 months and were at higher risk of disability accumulation.