Real-World Safety of MS Therapies: Insights from the Austrian MS Treatment Registry

Registry data from the Austrian MS Treatment Registry show that real-world adverse event (AE) patterns across disease-modifying therapies (DMTs) largely mirror clinical trial expectations while adding population context that informs safety assessment.

The registry consolidates clinician-reported AEs and serious adverse events (SAEs) captured during routine care, offering direct insight into treatment-limiting toxicity and on-treatment monitoring needs.

The AMSTR dataset includes 7,913 patients (67.7% female; median age 37 years [IQR 29–45]) with biannual data collection from August 2006 through July 2025 and coverage from more than 100 certified MS centers in Austria, anchoring exposure denominators for rate calculations. The registry prospectively recorded prespecified safety endpoints (SAEs and predefined categories of infections and neoplasms) using standardized AE/SAE definitions and biannual clinician-reported case ascertainment across centers.

AEs and SAEs in AMSTR displayed class- and drug-specific patterns with measurable implications for discontinuation and monitoring. Alemtuzumab showed the highest proportion of immune-related AEs (41/90, 45.5%), including thyroid disorders (24/90, 26.7%), while overall SAE rates remained low across most DMTs. Hematologic events were notable with sphingosine-1-phosphate (S1P) receptor modulators and infusion-related events with monoclonal antibodies. Neoplasm rates were uniformly low but detectable with S1P modulators (fingolimod 31/2,129, 1.4%). Treatment discontinuation was captured with reasons linked to tolerability and AE burden, underscoring the registry’s relevance for adherence and real-world persistence.

Comparative safety profiling in AMSTR identifies infections as the dominant event across several high-efficacy agents, with reported infection rates in cladribine (21/458, 4.6%), natalizumab (123/2,021, 6.1%), ocrelizumab (27/698, 3.9%) and ofatumumab (16/792, 2%). Gastrointestinal AEs were most frequent with dimethyl fumarate (364/2,572, 14.2%) and teriflunomide (78/781, 10%), and blood-system abnormalities predominated with fingolimod (245/2,129, 11.5%). These drug-specific signals support head-to-head safety judgements that complement efficacy-driven treatment selection.

AMSTR observations in special populations did not identify novel safety signals: pregnancy-exposure reports and older-age subgroup analyses showed event distributions consistent with the overall registry pattern and no emergent signals for neoplasms or atypical infections.

Overall, AMSTR reaffirms established DMT benefit–risk profiles and supplies actionable safety granularity for routine care.