L Zhovtis Ryerson1, T C Frohman2, J Foley3, I Kister1, B Weinstock-Guttman4, C Tornatore5, K Pandey6, S Donnelly7, S Pawate8, R Bomprezzi9, D Smith10, C Kolb4, S Qureshi2, D Okuda2, J Kalina1, Z Rimler1, R Green6, N Monson2, T Hoyt3, M Bradshaw8, J Fallon1, E Chamot11, M Bucello4, S Beh2, G Cutter11, E Major12, J Herbert1, E M Frohman13. 1. Department of Neurology, Langone Medical Center, New York University, New York, New York, USA. 2. Departments of Neurology & Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas, USA. 3. Rocky Mountain MS Clinic, Salt Lake City, Utah, USA. 4. University of Buffalo, Buffalo, New York, USA. 5. Georgetown University, Washington DC, USA. 6. Barnabas Health MS Center, Livingston, New Jersey, USA. 7. CUNY Graduate Center, New York, New York, USA. 8. Vanderbilt University Medical Center, Nashville, Tennessee, USA. 9. University of Massachusetts School of Medicine, Worcester, Massachusetts, USA. 10. Multiple Sclerosis Center of Connecticut, Norwich, Connecticut, USA. 11. University of Alabama School of Public Health, Birmingham, Alabama, USA. 12. National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA. 13. Departments of Neurology & Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas, USA Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, USA Department of Bioengineering, University of Texas at Dallas, Dallas, Texas, USA Department of Behavioural and Brain Sciences, University of Texas at Dallas, Dallas, Texas, USA.
Abstract
BACKGROUND: Natalizumab (NTZ), a monoclonal antibody to human α4β1/β7 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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
BACKGROUND:Natalizumab (NTZ), a monoclonal antibody to human α4β1/β7 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 EIDpatients (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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/