Epoch Analysis of On-Treatment Disability Progression Events over Time in the Tysabri Observational Program (TOP)

PLoS One. 2016 Jan 15;11(1):e0144834. doi: 10.1371/journal.pone.0144834. eCollection 2016.


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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Disability Evaluation
  • Disabled Persons*
  • Disease Progression
  • Female
  • Humans
  • Immunologic Factors / therapeutic use*
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / diagnosis
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Natalizumab / therapeutic use*
  • Time Factors
  • Treatment Outcome


  • Immunologic Factors
  • Natalizumab

Grant support

The TOP study is funded by Biogen (www.biogen.com); Biogen employees had a role in study design, data collection, and analysis. Biogen reviewed and provided feedback on the manuscript to the authors. Biogen also provided funding for editorial support in the development of this manuscript (provided by Nolan Campbell of Biogen and Joshua Safran and Melissa Austin of Infusion Communications, listed in the Acknowledgments). All Biogen employees listed as authors meet ICMJE authorship criteria. All authors have contributed sufficiently to the project to be included as authors and have read and approved the manuscript.