Journal of Neurology

, Volume 259, Issue 5, pp 898–905

Additional efficacy endpoints from pivotal natalizumab trials in relapsing-remitting MS


    • Jacobs Neurological Institute
  • Steven L. Galetta
    • University of Pennsylvania Medical Center
  • Gavin Giovannoni
    • Barts and The London School of Medicine and DentistryQueen Mary University of London
  • Eva Havrdova
    • Department of Neurology and Centre of Clinical NeuroscienceFirst Faculty of Medicine and General University Hospital, Charles University
  • Michael Hutchinson
    • St Vincent’s University Hospital
  • Ludwig Kappos
    • NeurologyUniversity Hospital Basel
  • Paul W. O’Connor
    • St. Michael’s Hospital
  • J. Theodore Phillips
    • MS Center at Texas Neurology
  • Chris Polman
    • VU Medical Centre
  • William H. Stuart
    • MS Center of Atlanta
  • Frances Lynn
    • Biogen Idec Inc
  • Christophe Hotermans
    • Biogen Idec Inc
Original Communication

DOI: 10.1007/s00415-011-6275-7

Cite this article as:
Weinstock-Guttman, B., Galetta, S.L., Giovannoni, G. et al. J Neurol (2012) 259: 898. doi:10.1007/s00415-011-6275-7


Standard clinical endpoints in multiple sclerosis (MS) studies, such as disability progression defined by the expanded disability status scale (EDSS) and annualized relapse rate, may not fully reflect all aspects of therapeutic benefit experienced by patients. Pivotal studies showed that natalizumab is effective both as monotherapy (AFFIRM study) and in combination with interferon beta-1a (IFNβ-1a) (SENTINEL study) in patients with relapsing MS. We present AFFIRM and SENTINEL data demonstrating the efficacy of natalizumab on prespecified tertiary endpoints, including extent of confirmed change in EDSS score from baseline, time to sustained progression to EDSS milestone scores, hospitalizations, corticosteroid use, and time to confirmed progression of cognitive deficits. Natalizumab significantly reduced changes in EDSS scores (P < 0.001) and proportion of patients progressing to an EDSS score ≥4.0 (P < 0.001) and ≥6.0 (P = 0.002) compared with placebo. Natalizumab + IFNβ-1a significantly reduced changes in EDSS scores compared with placebo + IFNβ-1a (P = 0.011). Based on 0.5 standard deviation change in paced auditory serial addition test-3 score, natalizumab treatment reduced the risk of confirmed progression of cognitive deficits by 43% compared with placebo (HR 0.57 [95% CI 0.37, 0.89], P = 0.013); however, no significant difference between groups was seen in SENTINEL. Natalizumab, both as monotherapy and in combination with IFNβ-1a, significantly reduced the annualized rate of MS-related hospitalizations (by 64 and 61%, respectively) and the annualized rate of relapses severe enough to require steroid treatment (by 69 and 61%, respectively) compared with placebo and placebo + IFNβ-1a (P < 0.001). These analyses underline beneficial effects of natalizumab therapy in relapsing MS patients.


Multiple sclerosisNatalizumabOutcomesCognitive functionHospitalizationCorticosteroids

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© Springer-Verlag 2011