Journal of Neurology

, Volume 259, Issue 5, pp 898–905

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

  • Bianca Weinstock-Guttman
  • Steven L. Galetta
  • Gavin Giovannoni
  • Eva Havrdova
  • Michael Hutchinson
  • Ludwig Kappos
  • Paul W. O’Connor
  • J. Theodore Phillips
  • Chris Polman
  • William H. Stuart
  • Frances Lynn
  • Christophe Hotermans
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

Abstract

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.

Keywords

Multiple sclerosisNatalizumabOutcomesCognitive functionHospitalizationCorticosteroids

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Bianca Weinstock-Guttman
    • 1
  • Steven L. Galetta
    • 2
  • Gavin Giovannoni
    • 3
  • Eva Havrdova
    • 4
  • Michael Hutchinson
    • 5
  • Ludwig Kappos
    • 6
  • Paul W. O’Connor
    • 7
  • J. Theodore Phillips
    • 8
  • Chris Polman
    • 9
  • William H. Stuart
    • 10
  • Frances Lynn
    • 11
  • Christophe Hotermans
    • 12
  1. 1.Jacobs Neurological InstituteBuffaloUSA
  2. 2.University of Pennsylvania Medical CenterPhiladelphiaUSA
  3. 3.Barts and The London School of Medicine and DentistryQueen Mary University of LondonLondonUK
  4. 4.Department of Neurology and Centre of Clinical NeuroscienceFirst Faculty of Medicine and General University Hospital, Charles UniversityPragueCzech Republic
  5. 5.St Vincent’s University HospitalDublinIreland
  6. 6.NeurologyUniversity Hospital BaselBaselSwitzerland
  7. 7.St. Michael’s HospitalTorontoCanada
  8. 8.MS Center at Texas NeurologyDallasUSA
  9. 9.VU Medical CentreAmsterdamThe Netherlands
  10. 10.MS Center of AtlantaAtlantaUSA
  11. 11.Biogen Idec IncMaidenheadUK
  12. 12.Biogen Idec IncWestonUSA