To evaluate clinical outcomes and safety of de-escalation from high effective therapies (HETs) to lower effective therapies in people with multiple sclerosis (PwMS).

HETs have significantly reduced relapse rates in PwMS. Older PwMS exhibit lower relapse activity yet remain on HET for years as it remains unknown when it is safe to de-escalate therapy.

Retrospective analysis was performed on PwMS who were de-escalated to moderate or low effective therapy after at least two years on HET without relapse activity. PwMS with a relapse or new T2 lesions on MRI in the two years after transition were categorized as the “breakthrough” group and the rest as the “stable” group. Risk factors for relapse activity were analyzed between the two groups.

In total, 58 patients were included (50 “stable” and 8 “breakthrough”). All “breakthrough” PwMS transitioned from natalizumab but occurred 6 months after transition or outside the rebound period. “Stable” PwMS transitioned from natalizumab (50%), ocrelizumab (49%) or alemtuzumab (1%). Most PwMS were de-escalated to cladribine (49%) or a fumarate (41%). There was no difference between gender, race, baseline disability, or de-escalation therapy between groups. “Stable” PwMS had higher average age at HET start (45.1 vs 35 years, p=0.006) and at de-escalation point (50.1 vs 39.6 years, p=0.0019) compared to “breakthrough” PwMS. Although not statistically significant, “stable” PwMS had higher average age at diagnosis (35.8 vs 29 years), longer exposure on HET (6 vs 4.5 years) and longer disease duration at de-escalation point (14.7 vs 9.9 years) compared to the “breakthrough” group.

These findings suggest that age may be an influential factor in determining stability after de-escalation and de-escalation from ocrelizumab appears to be safer than from natalizumab. Therefore, the decision to de-escalate should be based on individual patients’ characteristics.