Clinical outcomes in patients who discontinue natalizumab therapy after 2 years in the Tysabri® Observational Program (TOP)

Helmut Butzkueven, Maria Trojano, Ludwig Kappos, Tim Spelman, Heinz Wiendl, Karen Rosales, Ray Su, Stephanie Licata, Pei Ran Ho, Nolan Campbell, on behalf of the Tysabri® Observational Program (TOP) Investigators

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Background: Natalizumab is a highly efficacious therapy for relapsing–remitting multiple sclerosis (RRMS). Patients who discontinue natalizumab may experience return of MS disease activity. Objective: The aim of this study was to analyze predictors of post-natalizumab disease activity return. Methods: The Tysabri® Observational Program (TOP) is an ongoing observational study of natalizumab-treated RRMS patients. Patients discontinuing natalizumab are encouraged to remain in TOP. Results: Analyses included 3221 TOP patients. After ⩾2 years on natalizumab, relapse risk was twice as high for patients who switched to an oral therapy (n = 660, hazard ratio (HR) = 2.18, p < 0.001) and three times as high for patients who switched to an injectable therapy (n = 95, HR = 3.02, p < 0.001) as for those who stayed on natalizumab (n = 2466). Relapse rates after switching remained below pre-natalizumab rates. In patients who switched to an oral therapy, higher relapse risk was predicted by longer washout time, more pre-natalizumab relapses, higher Expanded Disability Status Scale score at natalizumab initiation, and shorter natalizumab treatment duration. Conclusion: Patients who stayed on natalizumab had better clinical outcomes than those who switched to an oral or injectable therapy after ⩾2 years on natalizumab. These results highlight modifiable risk factors for disease activity return (e.g. natalizumab treatment duration and washout duration) to consider when making treatment decisions.

Original languageEnglish
Article number1352458520917925
Number of pages10
JournalMultiple Sclerosis Journal
Publication statusAccepted/In press - May 2020


  • Discontinuation
  • disease-modifying therapy
  • multiple sclerosis
  • natalizumab
  • observational study
  • relapse

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