Cargando…
Efficacy and safety of monoclonal antibody therapy in patients with neuromyelitis optica spectrum disorder: A systematic review and network meta-analysis
INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is a devastating inflammatory CNS demyelinating disease. Two groups of monoclonal antibodies (mAbs) are used to prevent disease relapse, i.e., Food and Drug Administration (FDA)-approved mAbs (e.g., eculizumab satralizumab, inebilizumab),...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10110910/ https://www.ncbi.nlm.nih.gov/pubmed/37082442 http://dx.doi.org/10.3389/fneur.2023.1166490 |
_version_ | 1785027344735404032 |
---|---|
author | Aungsumart, Saharat Youngkong, Sitaporn Dejthevaporn, Charungthai Chaikledkaew, Usa Thadanipon, Kunlawat Tansawet, Amarit Khieukhajee, Jedsada Attia, John McKay, Gareth J. Thakkinstian, Ammarin |
author_facet | Aungsumart, Saharat Youngkong, Sitaporn Dejthevaporn, Charungthai Chaikledkaew, Usa Thadanipon, Kunlawat Tansawet, Amarit Khieukhajee, Jedsada Attia, John McKay, Gareth J. Thakkinstian, Ammarin |
author_sort | Aungsumart, Saharat |
collection | PubMed |
description | INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is a devastating inflammatory CNS demyelinating disease. Two groups of monoclonal antibodies (mAbs) are used to prevent disease relapse, i.e., Food and Drug Administration (FDA)-approved mAbs (e.g., eculizumab satralizumab, inebilizumab), and off-label mAb drugs (e.g., rituximab and tocilizumab). The FDA-approved mAbs have high efficacy but more expensive compared to the off-labels, and thus are less accessible. This systematic review and network meta-analysis (NMA) was to assess the efficacy and safety of both classes of mAbs compared to the current standard treatments. METHODS: Systematically searches were conducted in MEDLINE and SCOPUS from inception until July 2021. Randomized-controlled trials (RCTs) were eligible if they compared any pair of treatments (mAbs, immunosuppressive drugs, or placebo) in adult patients with NMOSD. Studies with AQP4-IgG positive or negative were used in the analysis. Probability of relapse and time to event were extracted from the Kaplan-Meier curves using Digitizer. These data were then converted into individual patient time-to-event data. A one-stage mixed-effect survival model was applied to estimate the median time to relapse and relative treatment effects using hazard ratios (HR). Two-stage NMA was used to determine post-treatment annualized relapse rate (ARR), expanded disability status score (EDSS) change, and serious adverse events (SAE). Risk of bias was assessed using the revised cochrane risk of bias tool. RESULTS: A total of 7 RCTs with 776 patients were eligible in the NMA. Five of the seven studies were rated low risk of bias. Both FDA-approved and off-label mAbs showed significantly lower risk of relapse than standard treatments, with HR (95% CI) of 0.13 (0.07, 0.24) and 0.16 (0.07, 0.37) respectively. In addition, the FDA-approved mAbs had 20% lower risk of relapse than the off-label mAbs, but this did not reach statistical significance. The ARRs were also lower in FDA-approved and off-label mAbs than the standard treatments with the mean-difference of−0.27 (-0.37,−0.16) and−0.31(-0.46,−0.16), respectively. CONCLUSION: The off-label mAbs may be used as the first-line treatment for improving clinical outcomes including disease relapse, ARR, and SAEs for NMOSD in countries where resources and accessibility of the FDA-approved mAbs are limited. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=283424, identifier: CRD42021283424. |
format | Online Article Text |
id | pubmed-10110910 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101109102023-04-19 Efficacy and safety of monoclonal antibody therapy in patients with neuromyelitis optica spectrum disorder: A systematic review and network meta-analysis Aungsumart, Saharat Youngkong, Sitaporn Dejthevaporn, Charungthai Chaikledkaew, Usa Thadanipon, Kunlawat Tansawet, Amarit Khieukhajee, Jedsada Attia, John McKay, Gareth J. Thakkinstian, Ammarin Front Neurol Neurology INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is a devastating inflammatory CNS demyelinating disease. Two groups of monoclonal antibodies (mAbs) are used to prevent disease relapse, i.e., Food and Drug Administration (FDA)-approved mAbs (e.g., eculizumab satralizumab, inebilizumab), and off-label mAb drugs (e.g., rituximab and tocilizumab). The FDA-approved mAbs have high efficacy but more expensive compared to the off-labels, and thus are less accessible. This systematic review and network meta-analysis (NMA) was to assess the efficacy and safety of both classes of mAbs compared to the current standard treatments. METHODS: Systematically searches were conducted in MEDLINE and SCOPUS from inception until July 2021. Randomized-controlled trials (RCTs) were eligible if they compared any pair of treatments (mAbs, immunosuppressive drugs, or placebo) in adult patients with NMOSD. Studies with AQP4-IgG positive or negative were used in the analysis. Probability of relapse and time to event were extracted from the Kaplan-Meier curves using Digitizer. These data were then converted into individual patient time-to-event data. A one-stage mixed-effect survival model was applied to estimate the median time to relapse and relative treatment effects using hazard ratios (HR). Two-stage NMA was used to determine post-treatment annualized relapse rate (ARR), expanded disability status score (EDSS) change, and serious adverse events (SAE). Risk of bias was assessed using the revised cochrane risk of bias tool. RESULTS: A total of 7 RCTs with 776 patients were eligible in the NMA. Five of the seven studies were rated low risk of bias. Both FDA-approved and off-label mAbs showed significantly lower risk of relapse than standard treatments, with HR (95% CI) of 0.13 (0.07, 0.24) and 0.16 (0.07, 0.37) respectively. In addition, the FDA-approved mAbs had 20% lower risk of relapse than the off-label mAbs, but this did not reach statistical significance. The ARRs were also lower in FDA-approved and off-label mAbs than the standard treatments with the mean-difference of−0.27 (-0.37,−0.16) and−0.31(-0.46,−0.16), respectively. CONCLUSION: The off-label mAbs may be used as the first-line treatment for improving clinical outcomes including disease relapse, ARR, and SAEs for NMOSD in countries where resources and accessibility of the FDA-approved mAbs are limited. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=283424, identifier: CRD42021283424. Frontiers Media S.A. 2023-04-04 /pmc/articles/PMC10110910/ /pubmed/37082442 http://dx.doi.org/10.3389/fneur.2023.1166490 Text en Copyright © 2023 Aungsumart, Youngkong, Dejthevaporn, Chaikledkaew, Thadanipon, Tansawet, Khieukhajee, Attia, McKay and Thakkinstian. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neurology Aungsumart, Saharat Youngkong, Sitaporn Dejthevaporn, Charungthai Chaikledkaew, Usa Thadanipon, Kunlawat Tansawet, Amarit Khieukhajee, Jedsada Attia, John McKay, Gareth J. Thakkinstian, Ammarin Efficacy and safety of monoclonal antibody therapy in patients with neuromyelitis optica spectrum disorder: A systematic review and network meta-analysis |
title | Efficacy and safety of monoclonal antibody therapy in patients with neuromyelitis optica spectrum disorder: A systematic review and network meta-analysis |
title_full | Efficacy and safety of monoclonal antibody therapy in patients with neuromyelitis optica spectrum disorder: A systematic review and network meta-analysis |
title_fullStr | Efficacy and safety of monoclonal antibody therapy in patients with neuromyelitis optica spectrum disorder: A systematic review and network meta-analysis |
title_full_unstemmed | Efficacy and safety of monoclonal antibody therapy in patients with neuromyelitis optica spectrum disorder: A systematic review and network meta-analysis |
title_short | Efficacy and safety of monoclonal antibody therapy in patients with neuromyelitis optica spectrum disorder: A systematic review and network meta-analysis |
title_sort | efficacy and safety of monoclonal antibody therapy in patients with neuromyelitis optica spectrum disorder: a systematic review and network meta-analysis |
topic | Neurology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10110910/ https://www.ncbi.nlm.nih.gov/pubmed/37082442 http://dx.doi.org/10.3389/fneur.2023.1166490 |
work_keys_str_mv | AT aungsumartsaharat efficacyandsafetyofmonoclonalantibodytherapyinpatientswithneuromyelitisopticaspectrumdisorderasystematicreviewandnetworkmetaanalysis AT youngkongsitaporn efficacyandsafetyofmonoclonalantibodytherapyinpatientswithneuromyelitisopticaspectrumdisorderasystematicreviewandnetworkmetaanalysis AT dejthevaporncharungthai efficacyandsafetyofmonoclonalantibodytherapyinpatientswithneuromyelitisopticaspectrumdisorderasystematicreviewandnetworkmetaanalysis AT chaikledkaewusa efficacyandsafetyofmonoclonalantibodytherapyinpatientswithneuromyelitisopticaspectrumdisorderasystematicreviewandnetworkmetaanalysis AT thadaniponkunlawat efficacyandsafetyofmonoclonalantibodytherapyinpatientswithneuromyelitisopticaspectrumdisorderasystematicreviewandnetworkmetaanalysis AT tansawetamarit efficacyandsafetyofmonoclonalantibodytherapyinpatientswithneuromyelitisopticaspectrumdisorderasystematicreviewandnetworkmetaanalysis AT khieukhajeejedsada efficacyandsafetyofmonoclonalantibodytherapyinpatientswithneuromyelitisopticaspectrumdisorderasystematicreviewandnetworkmetaanalysis AT attiajohn efficacyandsafetyofmonoclonalantibodytherapyinpatientswithneuromyelitisopticaspectrumdisorderasystematicreviewandnetworkmetaanalysis AT mckaygarethj efficacyandsafetyofmonoclonalantibodytherapyinpatientswithneuromyelitisopticaspectrumdisorderasystematicreviewandnetworkmetaanalysis AT thakkinstianammarin efficacyandsafetyofmonoclonalantibodytherapyinpatientswithneuromyelitisopticaspectrumdisorderasystematicreviewandnetworkmetaanalysis |