Abstract
Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease defined by attacks on the central nervous system that cause irreversible damage. Recent approval of NMOSD therapies warrants investigations of comparative efficacy to inform treatment decisions. Methods: A network meta-analysis (NMA) of all U.S. Food and Drug Administration-approved therapies (eculizumab, inebilizumab, and satralizumab) for adults with aquaporin-4 immunoglobulin G-positive (AQP4+) NMOSD was conducted via a systematic literature review (SLR) using data from randomized controlled trials (RCTs). Database searches of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were executed for the SLR. A fixed-effects proportional hazards Bayesian NMA was used to estimate relative treatment effects based on data extracted from RCTs identified during the SLR (search end date: 11 September 2020). Four unique RCTs (N-MOmentum, PREVENT, SAkuraSky, and SAkuraStar) were identified, and data from 29 publications were extracted for analysis. Network scenarios describing the most comparable patient population groups (such as by treatment settings) were evaluated in our analyses. Relative treatment effects were evaluated based on time-to-first relapse and were expressed as hazard ratios (HRs) with 95% credible intervals (CrIs). Results: In patients treated with a monoclonal antibody only, eculizumab was associated with a lower risk of relapse compared with satralizumab (HR 0.10, 95% CrI 0.01, 0.65) and inebilizumab (HR 0.11, 95% CrI 0.02, 0.68). In patients treated with monoclonal antibody with or without background immunosuppressive therapy (IST), patients treated with eculizumab ± IST were also less likely to relapse than patients treated with satralizumab ± IST (HR 0.24, 95% CrI 0.06, 0.98). Conclusion: The NMA results suggest that complement component 5 (C5) inhibition prevents NMOSD relapses more effectively than broader mechanisms of action.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 123-135 |
| Number of pages | 13 |
| Journal | Neurology and Therapy |
| Volume | 11 |
| Issue number | 1 |
| DOIs | |
| State | Published - Mar 2022 |
Keywords
- Aquaporin-4
- Eculizumab
- Inebilizumab
- Network meta-analysis
- Neuromyelitis optica
- Satralizumab
ASJC Scopus subject areas
- Neurology
- Clinical Neurology
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In: Neurology and Therapy, Vol. 11, No. 1, 03.2022, p. 123-135.
Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Network Meta-analysis of Food and Drug Administration-approved Treatment Options for Adults with Aquaporin-4 Immunoglobulin G-positive Neuromyelitis Optica Spectrum Disorder
AU - Wingerchuk, Dean M.
AU - Zhang, Ina
AU - Kielhorn, Adrian
AU - Royston, Minying
AU - Levy, Michael
AU - Fujihara, Kazuo
AU - Nakashima, Ichiro
AU - Tanvir, Imran
AU - Paul, Friedemann
AU - Pittock, Sean J.
N1 - Funding Information: Medical writing support was provided by Danielle E. Dalechek, MS, and Steven F. Merkel, PhD, of Oxford PharmaGenesis, Inc., Newtown, PA, and was funded by Alexion Pharmaceuticals, Inc. Funding Information: Imran Tanvir was an employee and stockholder of Alexion Pharmaceuticals during the development of this manuscript. Adrian Kielhorn is an employee and stockholder of Alexion Pharmaceuticals. Minying Royston was an employee and stockholder of Alexion Pharmaceuticals during the development of this manuscript. Michael Levy is an employee of Massachusetts General Hospital and has received consulting fees and grants from Alexion Pharmaceuticals, Viela Bio, and Genentech relevant to the manufacturers of the three drugs mentioned in this abstract. Ichiro Nakashima is an employee of Tohoku Medical and Pharmaceutical University and has received speech honoraria and consulting fees from Alexion Pharmaceuticals and Chugai Pharmaceutical. Kazuo Fujihara received honoraria for lectures and presentations from Alexion Pharmaceuticals, Inc., Roche/Chugai, and Viela Bio, and served on their advisory boards. Sean J Pittock and his institution have received honoraria and travel expenses for attending NMOSD advisory board meetings (MedImmune, Alexion Pharmaceuticals, Inc.); consulting fees (Alexion Pharmaceuticals, Inc., Euroimmun, Grifols, MedImmune); grant/research support (Alexion Pharmaceuticals, Inc., the Autoimmune Encephalitis Alliance, Euroimmun, Grifols, MedImmune); and other fees from the National Institutes of Health and the Guthy-Jackson Charitable Foundation. Dean M Wingerchuk is an employee of the Mayo Clinic and participated on a data safety monitoring or advisory board for Roche, Viela Bio, Genentech, Biogen, Reistone, TG Therapeutics, Celgene, and Novartis, with fees paid directly to himself; and for Alexion Pharmaceuticals, with fees paid to his institution. He received grants for clinical trials through Alexion Pharmaceuticals and TerumoBCT paid directly to his institution and was personally paid consulting fees by Mitsubishi Tanabe. Ina Zhang is an employee of PRECISIONheor, who received funding from Alexion Pharmaceuticals to support this work. Friedemann Paul is an employee of Charité-Universitätsmedizin Berlin and has received honoraria for lectures and research support from Alexion Pharmaceuticals. He has received grants for research support/recipient charité from German Ministry for Education and Research (BMBF), Deutsche Forschungsgemeinschaft (DFG), Einstein Foundation, the Guthy-Jackson Charitable Foundation, EU FP7 Framework Program, Biogen, Genzyme, Merck Serono, Novartis, Bayer, Roche, Parexel, and Almirall. He has received personal payment and travel expenses for lectures, presentations, and speakers’ bureaus from the Guthy-Jackson Foundation, Bayer, Biogen, Merck Serono, Sanofi Genzyme, Novartis, Viela Bio, Roche, UCB, Mitsubishi Tanabe, and Celgene. He has participated on an advisory board for Celgene, Roche, UCB, and Merck. He has offered unpaid support as an Academic Editor for PLos One and as Associate Editor for Neurology: Neuroimmunology & Neuroinflammation. Funding Information: Financial support for the research, authorship, and/or publication of this article: research funding and publication fees, including the journal’s Rapid Service Fee, were provided by Alexion, AstraZeneca Rare Disease. Medical writing support was provided by Danielle E. Dalechek, MS, and Steven F. Merkel, PhD, of Oxford PharmaGenesis, Inc., Newtown, PA, and was funded by Alexion Pharmaceuticals, Inc. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. Conception and design (all authors); acquisition of data (IZ, AK, MR); analysis or interpretation of data (all authors); preparation of manuscript (all authors); critical review of manuscript (all authors). The study sponsor reviewed the analysis plan and study manuscript. All aspects of the SLR (e.g., searches, screening, extraction), data management, processing, and analyses were conducted by PRECISIONheor. All final analytic decisions were made by study investigators. All authors have read and approved the final version of the manuscript. Imran Tanvir was an employee and stockholder of Alexion Pharmaceuticals during the development of this manuscript. Adrian Kielhorn is an employee and stockholder of Alexion Pharmaceuticals. Minying Royston was an employee and stockholder of Alexion Pharmaceuticals during the development of this manuscript. Michael Levy is an employee of Massachusetts General Hospital and has received consulting fees and grants from Alexion Pharmaceuticals, Viela Bio, and Genentech relevant to the manufacturers of the three drugs mentioned in this abstract. Ichiro Nakashima is an employee of Tohoku Medical and Pharmaceutical University and has received speech honoraria and consulting fees from Alexion Pharmaceuticals and Chugai Pharmaceutical. Kazuo Fujihara received honoraria for lectures and presentations from Alexion Pharmaceuticals, Inc., Roche/Chugai, and Viela Bio, and served on their advisory boards. Sean J Pittock and his institution have received honoraria and travel expenses for attending NMOSD advisory board meetings (MedImmune, Alexion Pharmaceuticals, Inc.); consulting fees (Alexion Pharmaceuticals, Inc., Euroimmun, Grifols, MedImmune); grant/research support (Alexion Pharmaceuticals, Inc., the Autoimmune Encephalitis Alliance, Euroimmun, Grifols, MedImmune); and other fees from the National Institutes of Health and the Guthy-Jackson Charitable Foundation. Dean M Wingerchuk is an employee of the Mayo Clinic and participated on a data safety monitoring or advisory board for Roche, Viela Bio, Genentech, Biogen, Reistone, TG Therapeutics, Celgene, and Novartis, with fees paid directly to himself; and for Alexion Pharmaceuticals, with fees paid to his institution. He received grants for clinical trials through Alexion Pharmaceuticals and TerumoBCT paid directly to his institution and was personally paid consulting fees by Mitsubishi Tanabe. Ina Zhang is an employee of PRECISIONheor, who received funding from Alexion Pharmaceuticals to support this work. Friedemann Paul is an employee of Charité-Universitätsmedizin Berlin and has received honoraria for lectures and research support from Alexion Pharmaceuticals. He has received grants for research support/recipient charité from German Ministry for Education and Research (BMBF), Deutsche Forschungsgemeinschaft (DFG), Einstein Foundation, the Guthy-Jackson Charitable Foundation, EU FP7 Framework Program, Biogen, Genzyme, Merck Serono, Novartis, Bayer, Roche, Parexel, and Almirall. He has received personal payment and travel expenses for lectures, presentations, and speakers’ bureaus from the Guthy-Jackson Foundation, Bayer, Biogen, Merck Serono, Sanofi Genzyme, Novartis, Viela Bio, Roche, UCB, Mitsubishi Tanabe, and Celgene. He has participated on an advisory board for Celgene, Roche, UCB, and Merck. He has offered unpaid support as an Academic Editor for PLos One and as Associate Editor for Neurology: Neuroimmunology & Neuroinflammation. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study. All data for this manuscript were publicly available and can be accessed using the criteria described in the Methods and Supplementary Material. Publisher Copyright: © 2021, The Author(s).
PY - 2022/3
Y1 - 2022/3
N2 - Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease defined by attacks on the central nervous system that cause irreversible damage. Recent approval of NMOSD therapies warrants investigations of comparative efficacy to inform treatment decisions. Methods: A network meta-analysis (NMA) of all U.S. Food and Drug Administration-approved therapies (eculizumab, inebilizumab, and satralizumab) for adults with aquaporin-4 immunoglobulin G-positive (AQP4+) NMOSD was conducted via a systematic literature review (SLR) using data from randomized controlled trials (RCTs). Database searches of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were executed for the SLR. A fixed-effects proportional hazards Bayesian NMA was used to estimate relative treatment effects based on data extracted from RCTs identified during the SLR (search end date: 11 September 2020). Four unique RCTs (N-MOmentum, PREVENT, SAkuraSky, and SAkuraStar) were identified, and data from 29 publications were extracted for analysis. Network scenarios describing the most comparable patient population groups (such as by treatment settings) were evaluated in our analyses. Relative treatment effects were evaluated based on time-to-first relapse and were expressed as hazard ratios (HRs) with 95% credible intervals (CrIs). Results: In patients treated with a monoclonal antibody only, eculizumab was associated with a lower risk of relapse compared with satralizumab (HR 0.10, 95% CrI 0.01, 0.65) and inebilizumab (HR 0.11, 95% CrI 0.02, 0.68). In patients treated with monoclonal antibody with or without background immunosuppressive therapy (IST), patients treated with eculizumab ± IST were also less likely to relapse than patients treated with satralizumab ± IST (HR 0.24, 95% CrI 0.06, 0.98). Conclusion: The NMA results suggest that complement component 5 (C5) inhibition prevents NMOSD relapses more effectively than broader mechanisms of action.
AB - Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease defined by attacks on the central nervous system that cause irreversible damage. Recent approval of NMOSD therapies warrants investigations of comparative efficacy to inform treatment decisions. Methods: A network meta-analysis (NMA) of all U.S. Food and Drug Administration-approved therapies (eculizumab, inebilizumab, and satralizumab) for adults with aquaporin-4 immunoglobulin G-positive (AQP4+) NMOSD was conducted via a systematic literature review (SLR) using data from randomized controlled trials (RCTs). Database searches of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were executed for the SLR. A fixed-effects proportional hazards Bayesian NMA was used to estimate relative treatment effects based on data extracted from RCTs identified during the SLR (search end date: 11 September 2020). Four unique RCTs (N-MOmentum, PREVENT, SAkuraSky, and SAkuraStar) were identified, and data from 29 publications were extracted for analysis. Network scenarios describing the most comparable patient population groups (such as by treatment settings) were evaluated in our analyses. Relative treatment effects were evaluated based on time-to-first relapse and were expressed as hazard ratios (HRs) with 95% credible intervals (CrIs). Results: In patients treated with a monoclonal antibody only, eculizumab was associated with a lower risk of relapse compared with satralizumab (HR 0.10, 95% CrI 0.01, 0.65) and inebilizumab (HR 0.11, 95% CrI 0.02, 0.68). In patients treated with monoclonal antibody with or without background immunosuppressive therapy (IST), patients treated with eculizumab ± IST were also less likely to relapse than patients treated with satralizumab ± IST (HR 0.24, 95% CrI 0.06, 0.98). Conclusion: The NMA results suggest that complement component 5 (C5) inhibition prevents NMOSD relapses more effectively than broader mechanisms of action.
KW - Aquaporin-4
KW - Eculizumab
KW - Inebilizumab
KW - Network meta-analysis
KW - Neuromyelitis optica
KW - Satralizumab
UR - http://www.scopus.com/inward/record.url?scp=85119271954&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85119271954&partnerID=8YFLogxK
U2 - 10.1007/s40120-021-00295-8
DO - 10.1007/s40120-021-00295-8
M3 - Article
AN - SCOPUS:85119271954
SN - 2193-8253
VL - 11
SP - 123
EP - 135
JO - Neurology and Therapy
JF - Neurology and Therapy
IS - 1
ER -