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

Objectives: 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). Material and Methods: 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. Results: 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. Conclusions: 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.