Journal of Neurology

, Volume 256, Issue 3, pp 405–415 | Cite as

The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL

  • M. Hutchinson
  • L. Kappos
  • P. A. Calabresi
  • C. Confavreux
  • G. Giovannoni
  • S. L. Galetta
  • E. Havrdova
  • F. D. Lublin
  • D. H. Miller
  • P. W. O’Connor
  • J. T. Phillips
  • C. H. Polman
  • E.-W. Radue
  • R. A. Rudick
  • W. H. Stuart
  • A. Wajgt
  • B. Weinstock-Guttman
  • D. R. Wynn
  • F. Lynn
  • M. A. Panzara
  • for the AFFIRM and SENTINEL Investigators
ORIGINAL COMMUNICATION

Abstract

The AFFIRM and SENTINEL studies showed that natalizumab was effective both as monotherapy and in combination with interferon beta (IFNβ)-1a in patients with relapsing multiple sclerosis (MS). Further analyses of AFFIRM and SENTINEL data were conducted to determine the efficacy of natalizumab in prespecified patient subgroups according to baseline characteristics: relapse history 1 year before randomization (1, 2, ≥ 3), Expanded Disability Status Scale score (≤ 3.5, > 3.5), number of T2 lesions (< 9, ≥ 9), presence of gadolinium-enhancing (Gd+) lesions (0, ≥ 1), age (< 40, ≥ 40) and gender (male, female). A post hoc analysis was conducted to determine the efficacy of natalizumab in patients with highly active disease (i. e., ≥ 2 relapses in the year before study entry and ≥ 1 Gd+ lesion at study entry). In both AFFIRM and SENTINEL studies natalizumab reduced the annualized relapse rates across all subgroups (except the small subgroups with < 9 baseline T2 lesions) over 2 years. In AFFIRM, natalizumab significantly reduced the risk of sustained disability progression in most subgroups. In SENTINEL, natalizumab significantly reduced the risk of sustained disability progression in the following subgroups: ≥ 9 T2 lesions at baseline, ≥ 1 Gd+ lesions at baseline, female patients and patients < 40 years of age. Natalizumab reduced the risk of disability progression by 64 % and relapse rate by 81 % in treatment- naive patients with highly active disease and by 58 % and 76 %, respectively, in patients with highly active disease despite IFNβ-1a treatment. These results indicate that natalizumab is effective in reducing disability progres- sion and relapses in patients with relapsing MS, particularly in patients with highly active disease.

Key words

multiple sclerosis natalizumab interferon beta-1a subgroup analysis highly active relapsing multiple sclerosis 

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Copyright information

© Steinkopff-Verlag 2009

Authors and Affiliations

  • M. Hutchinson
    • 1
  • L. Kappos
    • 2
  • P. A. Calabresi
    • 3
  • C. Confavreux
    • 4
  • G. Giovannoni
    • 5
  • S. L. Galetta
    • 6
  • E. Havrdova
    • 7
  • F. D. Lublin
    • 8
  • D. H. Miller
    • 5
  • P. W. O’Connor
    • 9
  • J. T. Phillips
    • 10
  • C. H. Polman
    • 11
  • E.-W. Radue
    • 2
  • R. A. Rudick
    • 12
  • W. H. Stuart
    • 13
  • A. Wajgt
    • 14
  • B. Weinstock-Guttman
    • 15
  • D. R. Wynn
    • 16
  • F. Lynn
    • 17
  • M. A. Panzara
    • 17
  • for the AFFIRM and SENTINEL Investigators
  1. 1.Dept. of NeurologySt. Vincent’s University HospitalDublinIreland
  2. 2.Dept. of NeurologyUniversity Hospital BaselBaselSwitzerland
  3. 3.Dept. of NeurologyThe Johns Hopkins University School of MedicineBaltimoreUSA
  4. 4.Hôpital NeurologiqueLyonFrance
  5. 5.Institute of NeurologyLondonUnited Kingdom
  6. 6.Dept. of NeurologyUniversity of Pennsylvania, School of MedicinePhiladelphiaUSA
  7. 7.General Teaching HospitalPragueCzech Republic
  8. 8.Mt. Sinai School of MedicineNew YorkUSA
  9. 9.St. Michael’s HospitalToronto, OntarioUSA
  10. 10.Multiple Sclerosis Center at Texas NeurologyDallasUSA
  11. 11.Vrije Universiteit Medical CenterAmsterdamThe Netherlands
  12. 12.Mellen Center for Multiple Sclerosis ResearchCleveland Clinic FoundationClevelandUSA
  13. 13.MS Center of AtlantaAtlantaUSA
  14. 14.Silesian Medical UniversityKatowicePoland
  15. 15.Baird Multiple Sclerosis CenterState University of New York at BuffaloBuffaloUSA
  16. 16.Consultants in NeurologyMultiple Sclerosis CenterNorthbrookUSA
  17. 17.Biogen IdecCambridgeUSA

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