Cargando…

Real-World Effectiveness of Natalizumab Extended Interval Dosing in a French Cohort

INTRODUCTION: Natalizumab, a therapy for relapsing–remitting multiple sclerosis (RRMS), is associated with a risk of progressive multifocal leukoencephalopathy (PML). Over the last several years, practitioners have used off-label extended interval dosing (EID) of natalizumab to reduce PML risk, desp...

Descripción completa

Detalles Bibliográficos
Autores principales: Pelle, Juliette, Briant, Anais R., Branger, Pierre, Derache, Nathalie, Arnaud, Charlotte, Lebrun-Frenay, Christine, Cohen, Mikael, Mondot, Lydiane, De Seze, Jerome, Bigaut, Kevin, Collongues, Nicolas, Kremer, Laurent, Ricard, Damien, Bompaire, Flavie, Ohlmann, Charlotte, Sallansonnet-Froment, Magali, Ciron, Jonathan, Biotti, Damien, Pignolet, Beatrice, Parienti, Jean-Jacques, Defer, Gilles
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Healthcare 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10043118/
https://www.ncbi.nlm.nih.gov/pubmed/36763307
http://dx.doi.org/10.1007/s40120-023-00440-5
_version_ 1784913073689067520
author Pelle, Juliette
Briant, Anais R.
Branger, Pierre
Derache, Nathalie
Arnaud, Charlotte
Lebrun-Frenay, Christine
Cohen, Mikael
Mondot, Lydiane
De Seze, Jerome
Bigaut, Kevin
Collongues, Nicolas
Kremer, Laurent
Ricard, Damien
Bompaire, Flavie
Ohlmann, Charlotte
Sallansonnet-Froment, Magali
Ciron, Jonathan
Biotti, Damien
Pignolet, Beatrice
Parienti, Jean-Jacques
Defer, Gilles
author_facet Pelle, Juliette
Briant, Anais R.
Branger, Pierre
Derache, Nathalie
Arnaud, Charlotte
Lebrun-Frenay, Christine
Cohen, Mikael
Mondot, Lydiane
De Seze, Jerome
Bigaut, Kevin
Collongues, Nicolas
Kremer, Laurent
Ricard, Damien
Bompaire, Flavie
Ohlmann, Charlotte
Sallansonnet-Froment, Magali
Ciron, Jonathan
Biotti, Damien
Pignolet, Beatrice
Parienti, Jean-Jacques
Defer, Gilles
author_sort Pelle, Juliette
collection PubMed
description INTRODUCTION: Natalizumab, a therapy for relapsing–remitting multiple sclerosis (RRMS), is associated with a risk of progressive multifocal leukoencephalopathy (PML). Over the last several years, practitioners have used off-label extended interval dosing (EID) of natalizumab to reduce PML risk, despite the absence of a large-scale efficacy evaluation. METHODS: We conducted a retrospective, multicenter cohort study among adults with RRMS receiving stable standard interval dosing (SID), defined as a ≥ 12-month consecutive period of ≥ 11 natalizumab infusions/year in France. We compared the 12-month risk difference of remaining relapse-free (primary endpoint) between patients who switched to EID (≤ 9 natalizumab infusions) and those who remained on SID, with a noninferiority margin of − 11%. We used propensity score methods such as inverse probability treatment weighting (IPTW) and 1:1 propensity score matching (PSM). Secondary endpoints were annualized relapse rate, disease progression, and safety. RESULTS: Baseline characteristics were similar between patients receiving EID (n = 147) and SID (n = 156). The proportion of relapse-free patients 12 months postbaseline was 142/147 in the EID (96.6%) and 144/156 in the SID group (92.3%); risk difference (95% CI) 4.3% (− 1.3 to 9.8%); p < 0.001 for non-inferiority. There were no significant differences between relapse rates (0.043 vs. 0.083 per year, respectively; p = 0.14) or Expanded Disability Status Scale mean scores (2.43 vs. 2.72, respectively; p = 0.18); anti-JC virus index values were similar (p = 0.23); and no instances of PML were reported. The comparisons using IPTW (n = 306) and PSM (n = 204) were consistent. CONCLUSION: These results support the pertinence of using an EID strategy for RRMS patients treated with natalizumab. CLINICAL TRIALS: gov identifier (NCT04580381). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40120-023-00440-5.
format Online
Article
Text
id pubmed-10043118
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Springer Healthcare
record_format MEDLINE/PubMed
spelling pubmed-100431182023-03-29 Real-World Effectiveness of Natalizumab Extended Interval Dosing in a French Cohort Pelle, Juliette Briant, Anais R. Branger, Pierre Derache, Nathalie Arnaud, Charlotte Lebrun-Frenay, Christine Cohen, Mikael Mondot, Lydiane De Seze, Jerome Bigaut, Kevin Collongues, Nicolas Kremer, Laurent Ricard, Damien Bompaire, Flavie Ohlmann, Charlotte Sallansonnet-Froment, Magali Ciron, Jonathan Biotti, Damien Pignolet, Beatrice Parienti, Jean-Jacques Defer, Gilles Neurol Ther Original Research INTRODUCTION: Natalizumab, a therapy for relapsing–remitting multiple sclerosis (RRMS), is associated with a risk of progressive multifocal leukoencephalopathy (PML). Over the last several years, practitioners have used off-label extended interval dosing (EID) of natalizumab to reduce PML risk, despite the absence of a large-scale efficacy evaluation. METHODS: We conducted a retrospective, multicenter cohort study among adults with RRMS receiving stable standard interval dosing (SID), defined as a ≥ 12-month consecutive period of ≥ 11 natalizumab infusions/year in France. We compared the 12-month risk difference of remaining relapse-free (primary endpoint) between patients who switched to EID (≤ 9 natalizumab infusions) and those who remained on SID, with a noninferiority margin of − 11%. We used propensity score methods such as inverse probability treatment weighting (IPTW) and 1:1 propensity score matching (PSM). Secondary endpoints were annualized relapse rate, disease progression, and safety. RESULTS: Baseline characteristics were similar between patients receiving EID (n = 147) and SID (n = 156). The proportion of relapse-free patients 12 months postbaseline was 142/147 in the EID (96.6%) and 144/156 in the SID group (92.3%); risk difference (95% CI) 4.3% (− 1.3 to 9.8%); p < 0.001 for non-inferiority. There were no significant differences between relapse rates (0.043 vs. 0.083 per year, respectively; p = 0.14) or Expanded Disability Status Scale mean scores (2.43 vs. 2.72, respectively; p = 0.18); anti-JC virus index values were similar (p = 0.23); and no instances of PML were reported. The comparisons using IPTW (n = 306) and PSM (n = 204) were consistent. CONCLUSION: These results support the pertinence of using an EID strategy for RRMS patients treated with natalizumab. CLINICAL TRIALS: gov identifier (NCT04580381). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40120-023-00440-5. Springer Healthcare 2023-02-10 /pmc/articles/PMC10043118/ /pubmed/36763307 http://dx.doi.org/10.1007/s40120-023-00440-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by-nc/4.0/Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Original Research
Pelle, Juliette
Briant, Anais R.
Branger, Pierre
Derache, Nathalie
Arnaud, Charlotte
Lebrun-Frenay, Christine
Cohen, Mikael
Mondot, Lydiane
De Seze, Jerome
Bigaut, Kevin
Collongues, Nicolas
Kremer, Laurent
Ricard, Damien
Bompaire, Flavie
Ohlmann, Charlotte
Sallansonnet-Froment, Magali
Ciron, Jonathan
Biotti, Damien
Pignolet, Beatrice
Parienti, Jean-Jacques
Defer, Gilles
Real-World Effectiveness of Natalizumab Extended Interval Dosing in a French Cohort
title Real-World Effectiveness of Natalizumab Extended Interval Dosing in a French Cohort
title_full Real-World Effectiveness of Natalizumab Extended Interval Dosing in a French Cohort
title_fullStr Real-World Effectiveness of Natalizumab Extended Interval Dosing in a French Cohort
title_full_unstemmed Real-World Effectiveness of Natalizumab Extended Interval Dosing in a French Cohort
title_short Real-World Effectiveness of Natalizumab Extended Interval Dosing in a French Cohort
title_sort real-world effectiveness of natalizumab extended interval dosing in a french cohort
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10043118/
https://www.ncbi.nlm.nih.gov/pubmed/36763307
http://dx.doi.org/10.1007/s40120-023-00440-5
work_keys_str_mv AT pellejuliette realworldeffectivenessofnatalizumabextendedintervaldosinginafrenchcohort
AT briantanaisr realworldeffectivenessofnatalizumabextendedintervaldosinginafrenchcohort
AT brangerpierre realworldeffectivenessofnatalizumabextendedintervaldosinginafrenchcohort
AT derachenathalie realworldeffectivenessofnatalizumabextendedintervaldosinginafrenchcohort
AT arnaudcharlotte realworldeffectivenessofnatalizumabextendedintervaldosinginafrenchcohort
AT lebrunfrenaychristine realworldeffectivenessofnatalizumabextendedintervaldosinginafrenchcohort
AT cohenmikael realworldeffectivenessofnatalizumabextendedintervaldosinginafrenchcohort
AT mondotlydiane realworldeffectivenessofnatalizumabextendedintervaldosinginafrenchcohort
AT desezejerome realworldeffectivenessofnatalizumabextendedintervaldosinginafrenchcohort
AT bigautkevin realworldeffectivenessofnatalizumabextendedintervaldosinginafrenchcohort
AT collonguesnicolas realworldeffectivenessofnatalizumabextendedintervaldosinginafrenchcohort
AT kremerlaurent realworldeffectivenessofnatalizumabextendedintervaldosinginafrenchcohort
AT ricarddamien realworldeffectivenessofnatalizumabextendedintervaldosinginafrenchcohort
AT bompaireflavie realworldeffectivenessofnatalizumabextendedintervaldosinginafrenchcohort
AT ohlmanncharlotte realworldeffectivenessofnatalizumabextendedintervaldosinginafrenchcohort
AT sallansonnetfromentmagali realworldeffectivenessofnatalizumabextendedintervaldosinginafrenchcohort
AT cironjonathan realworldeffectivenessofnatalizumabextendedintervaldosinginafrenchcohort
AT biottidamien realworldeffectivenessofnatalizumabextendedintervaldosinginafrenchcohort
AT pignoletbeatrice realworldeffectivenessofnatalizumabextendedintervaldosinginafrenchcohort
AT parientijeanjacques realworldeffectivenessofnatalizumabextendedintervaldosinginafrenchcohort
AT defergilles realworldeffectivenessofnatalizumabextendedintervaldosinginafrenchcohort