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Research paper
Extended interval dosing of natalizumab in multiple sclerosis
  1. L Zhovtis Ryerson1,
  2. T C Frohman2,
  3. J Foley3,
  4. I Kister1,
  5. B Weinstock-Guttman4,
  6. C Tornatore5,
  7. K Pandey6,
  8. S Donnelly7,
  9. S Pawate8,
  10. R Bomprezzi9,
  11. D Smith10,
  12. C Kolb4,
  13. S Qureshi2,
  14. D Okuda2,
  15. J Kalina1,
  16. Z Rimler1,
  17. R Green6,
  18. N Monson2,
  19. T Hoyt3,
  20. M Bradshaw8,
  21. J Fallon1,
  22. E Chamot11,
  23. M Bucello4,
  24. S Beh2,
  25. G Cutter11,
  26. E Major12,
  27. J Herbert1,
  28. E M Frohman2,13,14,15
  1. 1Department of Neurology, Langone Medical Center, New York University, New York, New York, USA
  2. 2Departments of Neurology & Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
  3. 3Rocky Mountain MS Clinic, Salt Lake City, Utah, USA
  4. 4University of Buffalo, Buffalo, New York, USA
  5. 5Georgetown University, Washington DC, USA
  6. 6Barnabas Health MS Center, Livingston, New Jersey, USA
  7. 7CUNY Graduate Center, New York, New York, USA
  8. 8Vanderbilt University Medical Center, Nashville, Tennessee, USA
  9. 9University of Massachusetts School of Medicine, Worcester, Massachusetts, USA
  10. 10Multiple Sclerosis Center of Connecticut, Norwich, Connecticut, USA
  11. 11University of Alabama School of Public Health, Birmingham, Alabama, USA
  12. 12National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA
  13. 13Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
  14. 14Department of Bioengineering, University of Texas at Dallas, Dallas, Texas, USA
  15. 15Department of Behavioural and Brain Sciences, University of Texas at Dallas, Dallas, Texas, USA
  1. Correspondence to Professor EM Frohman, Department of Neurology and Neurotherapeutics, University of Texas Southwestern School of Medicine, 5323 Harry Hines Blvd, Dallas, TX 75390, USA; Elliot.frohman{at}


Background Natalizumab (NTZ), a monoclonal antibody to human α4β17 integrin, is an effective therapy for multiple sclerosis (MS), albeit associated with progressive multifocal leukoencephalopathy (PML). Clinicians have been extending the dose of infusions with a hypothesis of reducing PML risk. The aim of the study is to evaluate the clinical consequences of reducing NTZ frequency of infusion up to 8 weeks 5 days.

Methods A retrospective chart review in 9 MS centres was performed in order to identify patients treated with extended interval dosing (EID) regimens of NTZ. Patients were stratified into 3 groups based on EID NTZ treatment schedule in individual centres: early extended dosing (EED; n=249) every 4 weeks 3 days to 6 weeks 6 days; late extended dosing (LED; n=274) every 7 weeks to 8 weeks 5 days; variable extended dosing (n=382) alternating between EED and LED. These groups were compared with patients on standard interval dosing (SID; n=1093) every 4 weeks.

Results 17% of patients on SID had new T2 lesions compared with 14% in EID (p=0.02); 7% of patients had enhancing T1 lesions in SID compared with 9% in EID (p=0.08); annualised relapse rate was 0.14 in the SID group, and 0.09 in the EID group. No evidence of clinical or radiographic disease activity was observed in 62% of SID and 61% of EID patients (p=0.83). No cases of PML were observed in EID group compared with 4 cases in SID cohort.

Conclusions Dosing intervals up to 8 weeks 5 days did not diminish effectiveness of NTZ therapy. Further monitoring is ongoing to evaluate if the risk of PML is reduced in patients on EID.

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