Long-Term Effectiveness of Natalizumab in Patients with Relapsing-Remitting Multiple Sclerosis Treated in the Routine Care in Greece: Results from the Multicenter, Observational 5-Year Prospective Study 'TOPICS Greece'

Abstract

Background and objectives: For chronic diseases like multiple sclerosis (MS), real-world evidence on long-term treatment outcomes is essential. The study aimed to provide long-term data on the safety and effectiveness of natalizumab in patients with relapsing-remitting MS (RRMS) treated in a routine care setting in Greece.

Methods: TOPICS Greece was a multicenter, single-country, prospective 5-year observational study.

Results: Between 19-Apr-2012 and 18-Dec-2014, 304 eligible adults [females: 63.2%; median age at natalizumab initiation: 38.0 years; median disease duration: 6.2 years; median Expanded Disability Status Scale (EDSS) score at baseline: 3.5] were enrolled in the study by 20 hospital-based neurologists. The 1-year annualized relapse rate (ARR) before treatment initiation was 1.859, while the ARR during the first year of treatment was 0.131, representing a significant 93% reduction (p < 0.001). The ARR over the median treatment period of 59.4 months was 0.109. Patients with ≤1 relapse in the pre-natalizumab year (46.1%) and those having received ≤1 prior disease-modifying therapy (57.9%) displayed significantly lower on-natalizumab ARR. The 1-, 2-, 3-, 4- and 5-year cumulative probabilities of EDSS progression were 3.2, 6.2, 9.7, 13.4, and 17.4%, respectively; the respective probabilities of EDSS disability improvement were 18.3, 25.1, 27.4, 28.0, and 30.1%. Over a median safety data collection period of 48.7 months, 4.6% of the patients experienced ≥ 1 serious adverse event, with infections (reported in 1.0%) being the most common.

Conclusion: In real-world settings in Greece, natalizumab displayed beneficial long-term effects on disease activity and disability progression consistent with previous studies with no new serious safety signals emerging.

Fig. 1

EDSS disability progression during study participation. Box-plots of the EDSS score at baseline and at the post-baseline timepoints (a). Numbers indicate median values; boxes extend from first to third quartile and whiskers from minimum to maximum score. Mean (SD) decrease from baseline derived from paired data along with p values (Wilcoxon signed-rank test) are indicated; median decreases were not shown as they were all zero. Kaplan-Meier estimated cumulative probability of 6-month sustained EDSS progression (b). Estimated cumulative probabilities at the 12-, 24-, 36-, 48-, and 60-month timepoints are tabulated below the graph. Kaplan-Meier estimated cumulative probability of 6-month sustained EDSS improvement (c). Estimated cumulative probabilities at the 12-, 24-, 36-, 48-, and 60-month timepoints are tabulated below the graph. Analyses in b and c was performed among eligible patients with a baseline and at least one post-baseline EDSS assessment (N = 286). EDSS expanded disability status scale, CI confidence interval, N number of patients with available data

Fig. 2

ARR and relapse-free rate during the study observation period. ARR during the indicated periods based on data from the overall eligible population (a). Kaplan-Meier estimated relapse-free rate during the study observation period (b). Estimated rates at the 12-, 24-, 36-, 48-, and 60-month timepoints are tabulated below the graph. ARR annualized relapse rate ratio, CI confidence interval, N number of patients with available data