Personalized extended interval dosing of natalizumab in MS: A prospective multicenter trial.

Adult Disability Evaluation Drug Administration Schedule Drug Monitoring Female Follow-Up Studies Humans Integrin alpha4beta1 / antagonists & inhibitors Magnetic Resonance Imaging Male Middle Aged Multiple Sclerosis / blood Natalizumab / administration & dosage Netherlands Neuroimaging Precision Medicine Prospective Studies Severity of Illness Index

Journal

Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060

Informations de publication

Date de publication:
11 08 2020
Historique:
received: 10 10 2019
accepted: 06 03 2020
pubmed: 22 7 2020
medline: 21 10 2020
entrez: 22 7 2020
Statut: ppublish

Résumé

To determine whether natalizumab efficacy is maintained when switching to personalized extended interval dosing based on individual natalizumab trough concentrations in patients with relapsing-remitting multiple sclerosis (RRMS). This was a prospective multicenter single-arm trial with 1 year follow-up and a 1-year extension phase. Participants were adult persons with RRMS treated with natalizumab without disease activity in the year prior to enrollment. The natalizumab treatment interval was based on longitudinal natalizumab trough concentrations. Patients received 3 monthly MRI scans, relapse assessments, and disability scoring during follow-up. The primary endpoint was the occurrence of gadolinium-enhancing lesions on MRI. Secondary endpoints were new/enlarging T2 lesions on MRI and relapses and progression on the Expanded Disability Status Scale (EDSS) during follow-up and extension phase. Sixty-one patients were included. Eighty-four percent extended the interval from a 4-week interval to a 5- to 7-week interval. No patient developed gadolinium-enhancing lesions (95% confidence interval [CI] 0%-7.4%) during follow-up. No new/enlarging T2 lesions (95% CI 0%-7.4%) or relapses (95% CI 0%-7.4%) were reported during follow-up and in the extension phase. Median EDSS was comparable at baseline (3.0, interquartile range [IQR] 2.0-5.0) and after follow-up (3.0, IQR 2.0-5.0). Personalized extended interval dosing did not induce recurrence of MS disease activity. Natalizumab efficacy was maintained in stable patients with RRMS receiving personalized extended interval dosing based on individual natalizumab concentrations. This study provides Class IV evidence that personalized extended interval dosing of natalizumab does not result in recurrence of disease activity in stable patients with RRMS.

Identifiants

DOI: 10.1212/WNL.0000000000009995 PMID: 32690785
pubmed: 32690785
pii: WNL.0000000000009995
doi: 10.1212/WNL.0000000000009995
doi:

Substances chimiques

Integrin alpha4beta1 0
Natalizumab 0

Types de publication

Clinical Trial Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e745-e754

Informations de copyright

© 2020 American Academy of Neurology.

Auteurs

Zoé L E van Kempen (ZLE)

From the Department of Neurology, Amsterdam MS Center (Z.L.E.v.K., B.W.v.O., B.M.J.U., J.K.), Department of Radiology (M.P.W., F.B.), and Neurochemistry Lab and Biobank, Department of Clinical Chemistry (C.E.T.), Amsterdam Neuroscience, and Department of Epidemiology and Biostatistics (B.I.L.-W.), Amsterdam University Medical Centers, Vrije Universiteit; Department of Neurology (E.L.J.H.), St. Antonius Hospital, Utrecht, the Netherlands; Department of Diagnostic and Interventional Neuroradiology (M.P.W.), Hannover Medical School, Germany; Department of Neurology (N.F.K.), OLVG Hospital, Amsterdam; Department of Neurology (J.P.M.), Rijnstate Hospital, Arnhem; Biologics Lab, Bioanalysis (A.d.V.), Sanquin Diagnostic Services; Department of Immunopathology (A.t.B., T.R.), Sanquin Research, Amsterdam; Landsteiner Laboratory (A.t.B., T.R.), Academic Medical Centre, University of Amsterdam, the Netherlands; and UCL Institutes of Neurology & Healthcare Engineering (F.B.), Queen Square, London, UK. z.vankempen@amsterdamumc.nl.
ORCID: 0000-0001-9557-5381

Erwin L J Hoogervorst (ELJ)

From the Department of Neurology, Amsterdam MS Center (Z.L.E.v.K., B.W.v.O., B.M.J.U., J.K.), Department of Radiology (M.P.W., F.B.), and Neurochemistry Lab and Biobank, Department of Clinical Chemistry (C.E.T.), Amsterdam Neuroscience, and Department of Epidemiology and Biostatistics (B.I.L.-W.), Amsterdam University Medical Centers, Vrije Universiteit; Department of Neurology (E.L.J.H.), St. Antonius Hospital, Utrecht, the Netherlands; Department of Diagnostic and Interventional Neuroradiology (M.P.W.), Hannover Medical School, Germany; Department of Neurology (N.F.K.), OLVG Hospital, Amsterdam; Department of Neurology (J.P.M.), Rijnstate Hospital, Arnhem; Biologics Lab, Bioanalysis (A.d.V.), Sanquin Diagnostic Services; Department of Immunopathology (A.t.B., T.R.), Sanquin Research, Amsterdam; Landsteiner Laboratory (A.t.B., T.R.), Academic Medical Centre, University of Amsterdam, the Netherlands; and UCL Institutes of Neurology & Healthcare Engineering (F.B.), Queen Square, London, UK.

Mike P Wattjes (MP)

From the Department of Neurology, Amsterdam MS Center (Z.L.E.v.K., B.W.v.O., B.M.J.U., J.K.), Department of Radiology (M.P.W., F.B.), and Neurochemistry Lab and Biobank, Department of Clinical Chemistry (C.E.T.), Amsterdam Neuroscience, and Department of Epidemiology and Biostatistics (B.I.L.-W.), Amsterdam University Medical Centers, Vrije Universiteit; Department of Neurology (E.L.J.H.), St. Antonius Hospital, Utrecht, the Netherlands; Department of Diagnostic and Interventional Neuroradiology (M.P.W.), Hannover Medical School, Germany; Department of Neurology (N.F.K.), OLVG Hospital, Amsterdam; Department of Neurology (J.P.M.), Rijnstate Hospital, Arnhem; Biologics Lab, Bioanalysis (A.d.V.), Sanquin Diagnostic Services; Department of Immunopathology (A.t.B., T.R.), Sanquin Research, Amsterdam; Landsteiner Laboratory (A.t.B., T.R.), Academic Medical Centre, University of Amsterdam, the Netherlands; and UCL Institutes of Neurology & Healthcare Engineering (F.B.), Queen Square, London, UK.

Nynke F Kalkers (NF)

From the Department of Neurology, Amsterdam MS Center (Z.L.E.v.K., B.W.v.O., B.M.J.U., J.K.), Department of Radiology (M.P.W., F.B.), and Neurochemistry Lab and Biobank, Department of Clinical Chemistry (C.E.T.), Amsterdam Neuroscience, and Department of Epidemiology and Biostatistics (B.I.L.-W.), Amsterdam University Medical Centers, Vrije Universiteit; Department of Neurology (E.L.J.H.), St. Antonius Hospital, Utrecht, the Netherlands; Department of Diagnostic and Interventional Neuroradiology (M.P.W.), Hannover Medical School, Germany; Department of Neurology (N.F.K.), OLVG Hospital, Amsterdam; Department of Neurology (J.P.M.), Rijnstate Hospital, Arnhem; Biologics Lab, Bioanalysis (A.d.V.), Sanquin Diagnostic Services; Department of Immunopathology (A.t.B., T.R.), Sanquin Research, Amsterdam; Landsteiner Laboratory (A.t.B., T.R.), Academic Medical Centre, University of Amsterdam, the Netherlands; and UCL Institutes of Neurology & Healthcare Engineering (F.B.), Queen Square, London, UK.

Jop P Mostert (JP)

From the Department of Neurology, Amsterdam MS Center (Z.L.E.v.K., B.W.v.O., B.M.J.U., J.K.), Department of Radiology (M.P.W., F.B.), and Neurochemistry Lab and Biobank, Department of Clinical Chemistry (C.E.T.), Amsterdam Neuroscience, and Department of Epidemiology and Biostatistics (B.I.L.-W.), Amsterdam University Medical Centers, Vrije Universiteit; Department of Neurology (E.L.J.H.), St. Antonius Hospital, Utrecht, the Netherlands; Department of Diagnostic and Interventional Neuroradiology (M.P.W.), Hannover Medical School, Germany; Department of Neurology (N.F.K.), OLVG Hospital, Amsterdam; Department of Neurology (J.P.M.), Rijnstate Hospital, Arnhem; Biologics Lab, Bioanalysis (A.d.V.), Sanquin Diagnostic Services; Department of Immunopathology (A.t.B., T.R.), Sanquin Research, Amsterdam; Landsteiner Laboratory (A.t.B., T.R.), Academic Medical Centre, University of Amsterdam, the Netherlands; and UCL Institutes of Neurology & Healthcare Engineering (F.B.), Queen Square, London, UK.

Birgit I Lissenberg-Witte (BI)

From the Department of Neurology, Amsterdam MS Center (Z.L.E.v.K., B.W.v.O., B.M.J.U., J.K.), Department of Radiology (M.P.W., F.B.), and Neurochemistry Lab and Biobank, Department of Clinical Chemistry (C.E.T.), Amsterdam Neuroscience, and Department of Epidemiology and Biostatistics (B.I.L.-W.), Amsterdam University Medical Centers, Vrije Universiteit; Department of Neurology (E.L.J.H.), St. Antonius Hospital, Utrecht, the Netherlands; Department of Diagnostic and Interventional Neuroradiology (M.P.W.), Hannover Medical School, Germany; Department of Neurology (N.F.K.), OLVG Hospital, Amsterdam; Department of Neurology (J.P.M.), Rijnstate Hospital, Arnhem; Biologics Lab, Bioanalysis (A.d.V.), Sanquin Diagnostic Services; Department of Immunopathology (A.t.B., T.R.), Sanquin Research, Amsterdam; Landsteiner Laboratory (A.t.B., T.R.), Academic Medical Centre, University of Amsterdam, the Netherlands; and UCL Institutes of Neurology & Healthcare Engineering (F.B.), Queen Square, London, UK.

Annick de Vries (A)

From the Department of Neurology, Amsterdam MS Center (Z.L.E.v.K., B.W.v.O., B.M.J.U., J.K.), Department of Radiology (M.P.W., F.B.), and Neurochemistry Lab and Biobank, Department of Clinical Chemistry (C.E.T.), Amsterdam Neuroscience, and Department of Epidemiology and Biostatistics (B.I.L.-W.), Amsterdam University Medical Centers, Vrije Universiteit; Department of Neurology (E.L.J.H.), St. Antonius Hospital, Utrecht, the Netherlands; Department of Diagnostic and Interventional Neuroradiology (M.P.W.), Hannover Medical School, Germany; Department of Neurology (N.F.K.), OLVG Hospital, Amsterdam; Department of Neurology (J.P.M.), Rijnstate Hospital, Arnhem; Biologics Lab, Bioanalysis (A.d.V.), Sanquin Diagnostic Services; Department of Immunopathology (A.t.B., T.R.), Sanquin Research, Amsterdam; Landsteiner Laboratory (A.t.B., T.R.), Academic Medical Centre, University of Amsterdam, the Netherlands; and UCL Institutes of Neurology & Healthcare Engineering (F.B.), Queen Square, London, UK.

Anja Ten Brinke (A)

From the Department of Neurology, Amsterdam MS Center (Z.L.E.v.K., B.W.v.O., B.M.J.U., J.K.), Department of Radiology (M.P.W., F.B.), and Neurochemistry Lab and Biobank, Department of Clinical Chemistry (C.E.T.), Amsterdam Neuroscience, and Department of Epidemiology and Biostatistics (B.I.L.-W.), Amsterdam University Medical Centers, Vrije Universiteit; Department of Neurology (E.L.J.H.), St. Antonius Hospital, Utrecht, the Netherlands; Department of Diagnostic and Interventional Neuroradiology (M.P.W.), Hannover Medical School, Germany; Department of Neurology (N.F.K.), OLVG Hospital, Amsterdam; Department of Neurology (J.P.M.), Rijnstate Hospital, Arnhem; Biologics Lab, Bioanalysis (A.d.V.), Sanquin Diagnostic Services; Department of Immunopathology (A.t.B., T.R.), Sanquin Research, Amsterdam; Landsteiner Laboratory (A.t.B., T.R.), Academic Medical Centre, University of Amsterdam, the Netherlands; and UCL Institutes of Neurology & Healthcare Engineering (F.B.), Queen Square, London, UK.

Bob W van Oosten (BW)

From the Department of Neurology, Amsterdam MS Center (Z.L.E.v.K., B.W.v.O., B.M.J.U., J.K.), Department of Radiology (M.P.W., F.B.), and Neurochemistry Lab and Biobank, Department of Clinical Chemistry (C.E.T.), Amsterdam Neuroscience, and Department of Epidemiology and Biostatistics (B.I.L.-W.), Amsterdam University Medical Centers, Vrije Universiteit; Department of Neurology (E.L.J.H.), St. Antonius Hospital, Utrecht, the Netherlands; Department of Diagnostic and Interventional Neuroradiology (M.P.W.), Hannover Medical School, Germany; Department of Neurology (N.F.K.), OLVG Hospital, Amsterdam; Department of Neurology (J.P.M.), Rijnstate Hospital, Arnhem; Biologics Lab, Bioanalysis (A.d.V.), Sanquin Diagnostic Services; Department of Immunopathology (A.t.B., T.R.), Sanquin Research, Amsterdam; Landsteiner Laboratory (A.t.B., T.R.), Academic Medical Centre, University of Amsterdam, the Netherlands; and UCL Institutes of Neurology & Healthcare Engineering (F.B.), Queen Square, London, UK.

Frederik Barkhof (F)

From the Department of Neurology, Amsterdam MS Center (Z.L.E.v.K., B.W.v.O., B.M.J.U., J.K.), Department of Radiology (M.P.W., F.B.), and Neurochemistry Lab and Biobank, Department of Clinical Chemistry (C.E.T.), Amsterdam Neuroscience, and Department of Epidemiology and Biostatistics (B.I.L.-W.), Amsterdam University Medical Centers, Vrije Universiteit; Department of Neurology (E.L.J.H.), St. Antonius Hospital, Utrecht, the Netherlands; Department of Diagnostic and Interventional Neuroradiology (M.P.W.), Hannover Medical School, Germany; Department of Neurology (N.F.K.), OLVG Hospital, Amsterdam; Department of Neurology (J.P.M.), Rijnstate Hospital, Arnhem; Biologics Lab, Bioanalysis (A.d.V.), Sanquin Diagnostic Services; Department of Immunopathology (A.t.B., T.R.), Sanquin Research, Amsterdam; Landsteiner Laboratory (A.t.B., T.R.), Academic Medical Centre, University of Amsterdam, the Netherlands; and UCL Institutes of Neurology & Healthcare Engineering (F.B.), Queen Square, London, UK.
ORCID: 0000-0003-3543-3706

Charlotte E Teunissen (CE)

From the Department of Neurology, Amsterdam MS Center (Z.L.E.v.K., B.W.v.O., B.M.J.U., J.K.), Department of Radiology (M.P.W., F.B.), and Neurochemistry Lab and Biobank, Department of Clinical Chemistry (C.E.T.), Amsterdam Neuroscience, and Department of Epidemiology and Biostatistics (B.I.L.-W.), Amsterdam University Medical Centers, Vrije Universiteit; Department of Neurology (E.L.J.H.), St. Antonius Hospital, Utrecht, the Netherlands; Department of Diagnostic and Interventional Neuroradiology (M.P.W.), Hannover Medical School, Germany; Department of Neurology (N.F.K.), OLVG Hospital, Amsterdam; Department of Neurology (J.P.M.), Rijnstate Hospital, Arnhem; Biologics Lab, Bioanalysis (A.d.V.), Sanquin Diagnostic Services; Department of Immunopathology (A.t.B., T.R.), Sanquin Research, Amsterdam; Landsteiner Laboratory (A.t.B., T.R.), Academic Medical Centre, University of Amsterdam, the Netherlands; and UCL Institutes of Neurology & Healthcare Engineering (F.B.), Queen Square, London, UK.

Bernard M J Uitdehaag (BMJ)

From the Department of Neurology, Amsterdam MS Center (Z.L.E.v.K., B.W.v.O., B.M.J.U., J.K.), Department of Radiology (M.P.W., F.B.), and Neurochemistry Lab and Biobank, Department of Clinical Chemistry (C.E.T.), Amsterdam Neuroscience, and Department of Epidemiology and Biostatistics (B.I.L.-W.), Amsterdam University Medical Centers, Vrije Universiteit; Department of Neurology (E.L.J.H.), St. Antonius Hospital, Utrecht, the Netherlands; Department of Diagnostic and Interventional Neuroradiology (M.P.W.), Hannover Medical School, Germany; Department of Neurology (N.F.K.), OLVG Hospital, Amsterdam; Department of Neurology (J.P.M.), Rijnstate Hospital, Arnhem; Biologics Lab, Bioanalysis (A.d.V.), Sanquin Diagnostic Services; Department of Immunopathology (A.t.B., T.R.), Sanquin Research, Amsterdam; Landsteiner Laboratory (A.t.B., T.R.), Academic Medical Centre, University of Amsterdam, the Netherlands; and UCL Institutes of Neurology & Healthcare Engineering (F.B.), Queen Square, London, UK.

Theo Rispens (T)

From the Department of Neurology, Amsterdam MS Center (Z.L.E.v.K., B.W.v.O., B.M.J.U., J.K.), Department of Radiology (M.P.W., F.B.), and Neurochemistry Lab and Biobank, Department of Clinical Chemistry (C.E.T.), Amsterdam Neuroscience, and Department of Epidemiology and Biostatistics (B.I.L.-W.), Amsterdam University Medical Centers, Vrije Universiteit; Department of Neurology (E.L.J.H.), St. Antonius Hospital, Utrecht, the Netherlands; Department of Diagnostic and Interventional Neuroradiology (M.P.W.), Hannover Medical School, Germany; Department of Neurology (N.F.K.), OLVG Hospital, Amsterdam; Department of Neurology (J.P.M.), Rijnstate Hospital, Arnhem; Biologics Lab, Bioanalysis (A.d.V.), Sanquin Diagnostic Services; Department of Immunopathology (A.t.B., T.R.), Sanquin Research, Amsterdam; Landsteiner Laboratory (A.t.B., T.R.), Academic Medical Centre, University of Amsterdam, the Netherlands; and UCL Institutes of Neurology & Healthcare Engineering (F.B.), Queen Square, London, UK.

Joep Killestein (J)

From the Department of Neurology, Amsterdam MS Center (Z.L.E.v.K., B.W.v.O., B.M.J.U., J.K.), Department of Radiology (M.P.W., F.B.), and Neurochemistry Lab and Biobank, Department of Clinical Chemistry (C.E.T.), Amsterdam Neuroscience, and Department of Epidemiology and Biostatistics (B.I.L.-W.), Amsterdam University Medical Centers, Vrije Universiteit; Department of Neurology (E.L.J.H.), St. Antonius Hospital, Utrecht, the Netherlands; Department of Diagnostic and Interventional Neuroradiology (M.P.W.), Hannover Medical School, Germany; Department of Neurology (N.F.K.), OLVG Hospital, Amsterdam; Department of Neurology (J.P.M.), Rijnstate Hospital, Arnhem; Biologics Lab, Bioanalysis (A.d.V.), Sanquin Diagnostic Services; Department of Immunopathology (A.t.B., T.R.), Sanquin Research, Amsterdam; Landsteiner Laboratory (A.t.B., T.R.), Academic Medical Centre, University of Amsterdam, the Netherlands; and UCL Institutes of Neurology & Healthcare Engineering (F.B.), Queen Square, London, UK.

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