De-Escalation Treatment Strategies From Natalizumab in Patients With Relapsing Multiple Sclerosis in Austria

This study aims to assess the efficacy of de-escalating from natalizumab (NTZ) to cladribine (CLAD), dimethyl fumarate (DMF), fingolimod (FTY), ponesimod (PONE), siponimod (SIPO) and teriflunomide (TERI).

We analyzed data from 388 patients in the Austrian MS Treatment Registry who initiated NTZ treatment and remained on therapy for at least 3 months before switching to one of the moderately effective therapies within 1 year. Patients were required to remain on the de-escalation therapy for at least 3 months.

Over a mean treatment duration of 42 months, the estimated ARR (annualized relapse rate) was 0.22 for highly effective therapy and 0.36 for de-escalation therapies over 61 months (p = 0.009). EDSS scores increased significantly from 2.8 to 3.1 during de-escalation (p < 0.001). Relapse probability during the treatment gap varied by interval: 14 patients (5.2%) in the < 3 months group, 14 patients (15.7%) in the 3-6 months group, and 13 patients (39.4%) in the 6-12 months group (p < 0.001). Male sex, lower baseline ARR (prior to the initiation of hDMT) and during transition, older age, shorter disease duration, and lower EDSS scores at both baseline and post-transition were significantly associated with a reduced risk of relapse and longer time to first relapse following de-escalation.

Our findings reveal an increased risk of relapses and EDSS worsening following de-escalation from NTZ. Additionally, relapse probability and EDSS progression were influenced by ARR during transition and EDSS scores at the end of the transition period.