Long-term outcome and predictors of long-term disease activity in natalizumab-treated patients with multiple sclerosis: real life data from the Austrian MS Treatment Registry

Objectives: To evaluate long-term effectiveness of natalizumab (NTZ) and to determine demographic, clinical, and radiological predictors regarding long-term disease activity (≥ 7 years) in a nationwide observational cohort, using data collected prospectively in a real-life setting.

Materials and methods: We analysed data from 230 patients from the Austrian Multiple Sclerosis Treatment Registry (AMSTR), who had started treatment with NTZ at any time since 2006 and stayed on NTZ for at least 7 years without treatment gap of more than three months.

Results: Estimated mean annualised relapse rates (ARR) over a mean treatment period of 9.3 years were 0.07 for NTZ. Sustained EDSS progression for 12 weeks was observed in 36 (19%) patients and for 24 weeks in 31 (16.3%) cases. Sustained EDSS regression for 12 and 24 weeks was seen in 45 (23.7%) and 42 (22.1%) cases. The baseline parameters ≥ 1 Gadolinium-enhancing MRI lesion(s) [incidence rate ratio (IRR) of 0.409 (95% CI 0.283-0.593), p = 0.001], ARR ≤ 1 in the prior 12 month before treatment initiation with NTZ [IRR of 0.353 (95% CI 0.200-0.623), p = 0.001] and EDSS ≤ 1 [incidence rate ratio (IRR) of 0.081 (95% CI 0.011-0.581), p = 0.012] were significantly associated with a reduced relapse risk, whereas a disease duration ≤ 5 years increased significantly the ARR [IRR of 1.851 (95% CI 1.249-2.743), p = 0.002]. The only predictive baseline parameter for experiencing EDSS progression (sustained for 12 and 24 weeks) was age > 35 years [HR of 2.482 (95% CI 1.110-5.549), p = 0.027, and HR of 2.492 (95% CI 1.039-5.978), p = 0.041, respectively].

Conclusions: These real-life data show a stable disease course regarding relapse activity and disease progression under NTZ treatment for more than 7 years. The main predictors for disease activity were higher relapse rate before treatment initiation, higher disability, shorter disease duration and absence of Gadolinium-enhancing MRI lesions at baseline. Older age at NTZ start was the only significant risk factor for disease progression over long-term.