Extended interval dosing of natalizumab in multiple sclerosis

Ryerson, Lana Zhovtis; Frohman, Teresa C.; Foley, John; Kister, Ilya; Weinstock‐Guttman, Bianca; Tornatore, Carlo; Pandey, Krupa; Donnelly, Seamus; Pawate, Siddharama; Bomprezzi, Roberto; Smith, Duncan R.; Kolb, Channa; Qureshi, Sara; Okuda, Darin T.; Kalina, J; Rimler, Zoe; Green, R.; Monson, Nancy; Hoyt, Tammy; Bradshaw, Marques L.; Fallon, Julia; Chamot, Eric; Bucello, Margaret A; Beh, Shin C.; Cutter, Gary; Major, Eugene O.; Herbert, Joseph; Frohman, Elliot M.

doi:10.1136/jnnp-2015-312940

Cited by 125 publications

(123 citation statements)

References 26 publications

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“…The risk of developing progressive multifocal leukoencephalopathy (PML) in a John Cunningham virus antibodynegative natalizumab-treated patient is estimated at 1: 10,000 36 and may be further reduced with extended interval dosing. 37 Natalizumab is otherwise generally well tolerated with a paucity of other potential side effects. In a population with rheumatoid arthritis, the risk of rituximab with long-term use is estimated to be 1:30,000.…”

Section: The Reported Safety Profiles Of Some Highly Effective Agentsmentioning

confidence: 99%

An argument for broad use of high efficacy treatments in early multiple sclerosis

Stankiewicz

Weiner

2020

Neurol Neuroimmunol Neuroinflamm

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Two different treatment paradigms are most often used in multiple sclerosis (MS). An escalation or induction approach is considered when treating a patient early in the disease course. An escalator prioritizes safety, whereas an inducer would favor efficacy. Our understanding of MS pathophysiology has evolved with novel in vivo and in vitro observations. The treatment landscape has also shifted significantly with the approval of over 10 new medications over the past decade alone. Here, we re-examine the treatment approach in light of these recent developments. We believe that recent work suggests that early prediction of the disease course is fraught, the amount of damage to the brain that MS causes is underappreciated, and its impact on patient function oftentimes is underestimated. These concerns, coupled with the recent availability of agents that allow a better therapeutic effect without compromising safety, lead us to believe that initiating higher efficacy treatments early is the best way to achieve the best possible long-term outcomes for people with MS. Multiple sclerosis following collection(s):This article, along with others on similar topics, appears in the Permissions & Licensing http://nn.neurology.org/misc/about.xhtml#permissions its entirety can be found online at: Information about reproducing this article in parts (figures,tables) or in Reprints http://nn.neurology.org/misc/addir.xhtml#reprintsus Information about ordering reprints can be found online: Academy of Neurology.. All rights reserved. Online

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Section: The Reported Safety Profiles Of Some Highly Effective Agentsmentioning

confidence: 99%

An argument for broad use of high efficacy treatments in early multiple sclerosis

Stankiewicz

Weiner

2020

Neurol Neuroimmunol Neuroinflamm

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“…The likelihood of developing PML is linked to certain risk factors including treatment duration, prior treatment with immunosuppressants and John Cunningham virus (JCV) serostatus . Recently, it has been suggested that a higher NTZ concentration (resulting in higher α‐4‐integrin receptor saturation) might be an additional risk factor for the development of PML . Although it is not confirmed that a higher NTZ concentration leads to an increased risk of PML, some neurologists are extending NTZ dose intervals with the aim of lowering the risk of PML .…”

Section: Introductionmentioning

confidence: 99%

John Cunningham virus conversion in relation to natalizumab concentration in multiple sclerosis patients

Kempen

Leurs

Vries

et al. 2017

Euro J of Neurology

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“…Extended interval dosing (EID) of natalizumab is an attempt to target a level of α4β 1 receptor saturation that maintains drug clinical effectiveness with the least effect possible on immunosurveillance in order to lower the PML risk. A retrospective chart review examined outcomes for 905 patients on EID versus 1,099 patients on standard interval dosing (SID) 55. In this analysis, EID ranged from dosing every 4 weeks 3 days to dosing every 8 weeks 5 days.…”

Section: Natalizumab Safety and Tolerabilitymentioning

confidence: 99%

The use of natalizumab for multiple sclerosis

Brandstadter¹,

Sand²

2017

NDT

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Natalizumab is a monoclonal antibody that acts as an α4 integrin antagonist to prevent leukocyte trafficking into the central nervous system. It is US Food and Drug Administration (FDA) approved for the treatment of relapsing–remitting multiple sclerosis (RRMS). Natalizumab demonstrated high efficacy in Phase III trials by reducing the annualized relapse rate, preventing multiple sclerosis (MS) lesion accumulation on magnetic resonance imaging, and decreasing the probability of sustained progression of disability. The leading safety concern with natalizumab is its association with progressive multifocal leukoencephalopathy (PML), a rare brain infection typically seen only in severely immunocompromised patients caused by reactivation of the John Cunningham virus (JCV). Careful analysis of risk factors for PML in natalizumab-treated MS patients, specifi-cally the presence of anti-JCV antibodies, has led to risk mitigation strategies to improve safety. Additional biomarkers are under investigation to further aid risk stratification. Natalizumab’s high efficacy and favorable tolerability profile have led to a broad use by MS physicians, as both first-and second-line treatments. This review discusses the natalizumab efficacy, safety, and tolerability and finishes with pragmatic considerations regarding its use in clinical practice.

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Extended interval dosing of natalizumab in multiple sclerosis

Abstract: 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.

Cited by 125 publications

References 26 publications

An argument for broad use of high efficacy treatments in early multiple sclerosis

An argument for broad use of high efficacy treatments in early multiple sclerosis

John Cunningham virus conversion in relation to natalizumab concentration in multiple sclerosis patients

The use of natalizumab for multiple sclerosis

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