Epoch analysis of on-treatment disability progression events over time in the Tysabri Observational Program (TOP)

Heinz S Wiendl, Helmut Butzkueven, Ludwig D Kappos, Maria Trojano, Fabio Pellegrini, Dominic Paes, Annie Zhang, Shibeshih Belachew

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Abstract

Objective: To evaluate the effect of natalizumab on disability progression beyond 2 years of treatment in clinical practice. Methods: Analyses included the 496 relapsing-remitting multiple sclerosis (RRMS) patients among 5122 patients in the Tysabri Observational Program (TOP) who had completed 4 continuous years of natalizumab treatment and had baseline (study enrollment) and postbaseline Expanded Disability Status Scale (EDSS) assessments. Proportions of patients with 6-month or 12-month confirmed ≥1.0-point EDSS progression relative to baseline were compared in treatment months 1-24 and 25-48. Sensitivity analyses compared progression rates in months 13-24 and 25-36. Results: Baseline characteristics appeared similar between the overall TOP population (N = 5122), patients who had completed 4 years of natalizumab treatment (n = 469), and patients eligible to complete 4 years in TOP who had discontinued natalizumab after 2 years of treatment (n = 514). Among 4-year completers, the proportion of patients with 6-month and 12-month confirmed EDSS progression decreased between months 1-24 and 25-48 of natalizumab treatment by 42% (from 10.9% to 6.3%; p < 0.01) and 52% (from 9.5% to 4.6%; p < 0.01), respectively. Few patients had 6-month or 12-month confirmed EDSS progression in both epochs (0.6% and 0.2%, respectively). Between months 13-24 and 25-36 of treatment, the proportion of patients with 6-month and 12-month confirmed EDSS progression decreased by 60% (from 7.5% to 3.0%; p < 0.01) and 58% (from 6.7% to 2.8%; p < 0.01), respectively. Significant reductions in disability progression events between months 13-24 and 25-36 were also observed in relapse-free patients. Conclusion: In this observational study, the disability progression rate decreased further beyond 2 years of natalizumab treatment. Patients who responded well and remained on continuous natalizumab therapy for over 4 years had sustained and potentially enhanced reductions in EDSS progression over time.

Original languageEnglish
Article numbere0144834
JournalPLoS ONE
Volume11
Issue number1
DOIs
Publication statusPublished - 1 Jan 2016

Cite this

Wiendl, H. S., Butzkueven, H., Kappos, L. D., Trojano, M., Pellegrini, F., Paes, D., Zhang, A., & Belachew, S. (2016). Epoch analysis of on-treatment disability progression events over time in the Tysabri Observational Program (TOP). PLoS ONE, 11(1), [e0144834]. https://doi.org/10.1371/journal.pone.0144834