Skip to main content
Top
Published in:

Open Access 09-05-2024 | Neuromyelitis Optica Spectrum Disease | REVIEW

Network Meta-analysis of Ravulizumab and Alternative Interventions for the Treatment of Neuromyelitis Optica Spectrum Disorder

Authors: Stacey L. Clardy, Sean J. Pittock, Orhan Aktas, Jin Nakahara, Noriko Isobe, Diego Centonze, Sami Fam, Adrian Kielhorn, Jeffrey C. Yu, Jeroen Jansen, Ina Zhang

Published in: Neurology and Therapy | Issue 3/2024

Login to get access

Abstract

Introduction

Anti-aquaporin-4 antibody-positive (AQP4-Ab+) neuromyelitis optica spectrum disorder (NMOSD) is a complement-mediated autoimmune disease in which unpredictable and relapsing attacks on the central nervous system cause irreversible and accumulating damage. Comparative efficacy of new NMOSD therapies, such as ravulizumab, with established therapies is critical in making informed treatment decisions.

Methods

Efficacy of ravulizumab relative to established AQP4-Ab+ NMOSD treatments, such as eculizumab, inebilizumab, and satralizumab, was evaluated in a Bayesian network meta-analysis (NMA). Data were extracted from trials identified by a systematic literature review. The final evidence base consisted of 17 publications representing five unique and global studies (PREVENT, N-MOmentum, SAkuraSky, SAkuraStar, and CHAMPION-NMOSD). The primary endpoint was time-to-first relapse; other outcomes included annualized relapse rates (ARRs).

Results

For patients receiving monotherapy (monoclonal antibody only), ravulizumab was associated with a lower risk of relapse than inebilizumab (hazard ratio [HR] 0.09, 95% credible interval [CrI] 0.02, 0.57) or satralizumab (HR 0.08, 95% CrI 0.01, 0.55) and was comparable to eculizumab (HR 0.86, 95% Crl 0.16, 4.52). Ravulizumab + immunosuppressive therapy (IST) was associated with a lower risk of relapse than satralizumab + IST (HR 0.15, 95% CrI 0.03, 0.78); the comparison with eculizumab + IST suggested no difference. No patients treated with inebilizumab received background IST and were thus excluded from analysis. The ARR with ravulizumab monotherapy was 98% lower compared with inebilizumab (rate ratio [RR] 0.02, 95% Crl 0.00, 0.38) and satralizumab (RR 0.02, 95% Crl 0.00, 0.42) monotherapies. The ARR with ravulizumab ± IST showed the strongest treatment-effect estimates compared with other interventions.

Conclusion

In the absence of head-to-head randomized controlled trials, NMA results suggest ravulizumab, a C5 inhibitor, is likely to be more effective in preventing NMOSD relapse in patients with AQP4-Ab+ NMOSD when compared with other treatments having different methods of action.
Appendix
Available only for authorised users
Literature
1.
go back to reference Jarius S, Ruprecht K, Wildemann B, et al. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: a multicentre study of 175 patients. J Neuroinflamm. 2012;9:14.CrossRef Jarius S, Ruprecht K, Wildemann B, et al. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: a multicentre study of 175 patients. J Neuroinflamm. 2012;9:14.CrossRef
2.
go back to reference Hyun JW, Kim Y, Kim SY, Lee MY, Kim SH, Kim HJ. Investigating the presence of interattack astrocyte damage in neuromyelitis optica spectrum disorder: longitudinal analysis of serum glial fibrillary acidic protein. Neurol Neuroimmunol Neuroinflamm. 2021;8(3):e965.CrossRefPubMedPubMedCentral Hyun JW, Kim Y, Kim SY, Lee MY, Kim SH, Kim HJ. Investigating the presence of interattack astrocyte damage in neuromyelitis optica spectrum disorder: longitudinal analysis of serum glial fibrillary acidic protein. Neurol Neuroimmunol Neuroinflamm. 2021;8(3):e965.CrossRefPubMedPubMedCentral
3.
go back to reference Pittock SJ, Berthele A, Fujihara K, et al. Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. N Engl J Med. 2019;381(7):614–25.CrossRefPubMed Pittock SJ, Berthele A, Fujihara K, et al. Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. N Engl J Med. 2019;381(7):614–25.CrossRefPubMed
4.
go back to reference Hamid SHM, Whittam D, Mutch K, et al. What proportion of AQP4-IgG-negative NMO spectrum disorder patients are MOG-IgG positive? A cross sectional study of 132 patients. J Neurol. 2017;264(10):2088–94.CrossRefPubMedPubMedCentral Hamid SHM, Whittam D, Mutch K, et al. What proportion of AQP4-IgG-negative NMO spectrum disorder patients are MOG-IgG positive? A cross sectional study of 132 patients. J Neurol. 2017;264(10):2088–94.CrossRefPubMedPubMedCentral
5.
6.
go back to reference Hinson SR, Romero MF, Popescu BF, et al. Molecular outcomes of neuromyelitis optica (NMO)-IgG binding to aquaporin-4 in astrocytes. Proc Natl Acad Sci U S A. 2012;109(4):1245–50.CrossRefPubMed Hinson SR, Romero MF, Popescu BF, et al. Molecular outcomes of neuromyelitis optica (NMO)-IgG binding to aquaporin-4 in astrocytes. Proc Natl Acad Sci U S A. 2012;109(4):1245–50.CrossRefPubMed
8.
go back to reference Levy M, Fujihara K, Palace J. New therapies for neuromyelitis optica spectrum disorder. Lancet Neurol. 2021;20(1):60–7.CrossRefPubMed Levy M, Fujihara K, Palace J. New therapies for neuromyelitis optica spectrum disorder. Lancet Neurol. 2021;20(1):60–7.CrossRefPubMed
9.
go back to reference Kim SH, Jang H, Park NY, et al. Discontinuation of immunosuppressive therapy in patients with neuromyelitis optica spectrum disorder with aquaporin-4 antibodies. Neurol Neuroimmunol Neuroinflamm. 2021;8(2):e947.CrossRefPubMedPubMedCentral Kim SH, Jang H, Park NY, et al. Discontinuation of immunosuppressive therapy in patients with neuromyelitis optica spectrum disorder with aquaporin-4 antibodies. Neurol Neuroimmunol Neuroinflamm. 2021;8(2):e947.CrossRefPubMedPubMedCentral
10.
go back to reference Akaishi T, Misu T, Takahashi T, et al. Progression pattern of neurological disability with respect to clinical attacks in anti-MOG antibody-associated disorders. J Neuroimmunol. 2021;351:577467.CrossRefPubMed Akaishi T, Misu T, Takahashi T, et al. Progression pattern of neurological disability with respect to clinical attacks in anti-MOG antibody-associated disorders. J Neuroimmunol. 2021;351:577467.CrossRefPubMed
11.
go back to reference Huda S, Whittam D, Bhojak M, Chamberlain J, Noonan C, Jacob A. Neuromyelitis optica spectrum disorders. Clin Med (Lond). 2019;19(2):169–76.CrossRefPubMed Huda S, Whittam D, Bhojak M, Chamberlain J, Noonan C, Jacob A. Neuromyelitis optica spectrum disorders. Clin Med (Lond). 2019;19(2):169–76.CrossRefPubMed
12.
go back to reference Duan T, Smith AJ, Verkman AS. Complement-dependent bystander injury to neurons in AQP4-IgG seropositive neuromyelitis optica. J Neuroinflamm. 2018;15(1):294.CrossRef Duan T, Smith AJ, Verkman AS. Complement-dependent bystander injury to neurons in AQP4-IgG seropositive neuromyelitis optica. J Neuroinflamm. 2018;15(1):294.CrossRef
13.
go back to reference Jarius S, Paul F, Weinshenker BG, Levy M, Kim HJ, Wildemann B. Neuromyelitis optica. Nat Rev Dis Primers. 2020;6(1):85.CrossRefPubMed Jarius S, Paul F, Weinshenker BG, Levy M, Kim HJ, Wildemann B. Neuromyelitis optica. Nat Rev Dis Primers. 2020;6(1):85.CrossRefPubMed
14.
go back to reference SOLIRIS® (eculizumab). Prescribing Information. Alexion Pharmaceuticals, Inc., Boston, MA; 2020 November. SOLIRIS® (eculizumab). Prescribing Information. Alexion Pharmaceuticals, Inc., Boston, MA; 2020 November.
15.
go back to reference ENSPRYNG® (satralizumab-mwge). Prescribing Information. Genentech, Inc., San Francisco; 2022 March. ENSPRYNG® (satralizumab-mwge). Prescribing Information. Genentech, Inc., San Francisco; 2022 March.
16.
go back to reference Uplizna® (inebilizumab-cdon). Prescribing Information. Horizon Therapeutics, Dublin, 2021 July. Uplizna® (inebilizumab-cdon). Prescribing Information. Horizon Therapeutics, Dublin, 2021 July.
17.
go back to reference Soliris: product information. European Medicines Agency, London, 2021. Soliris: product information. European Medicines Agency, London, 2021.
18.
go back to reference Yamamura T, Kleiter I, Fujihara K, et al. Trial of satralizumab in neuromyelitis optica spectrum disorder. N Engl J Med. 2019;381(22):2114–24.CrossRefPubMed Yamamura T, Kleiter I, Fujihara K, et al. Trial of satralizumab in neuromyelitis optica spectrum disorder. N Engl J Med. 2019;381(22):2114–24.CrossRefPubMed
19.
go back to reference Traboulsee A, Greenberg BM, Bennett JL, et al. Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomised, double-blind, multicentre, placebo-controlled phase 3 trial. Lancet Neurol. 2020;19(5):402–12.CrossRefPubMedPubMedCentral Traboulsee A, Greenberg BM, Bennett JL, et al. Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomised, double-blind, multicentre, placebo-controlled phase 3 trial. Lancet Neurol. 2020;19(5):402–12.CrossRefPubMedPubMedCentral
20.
go back to reference Cree BAC, Bennett JL, Kim HJ, et al. Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial. Lancet. 2019;394(10206):1352–63.CrossRefPubMed Cree BAC, Bennett JL, Kim HJ, et al. Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial. Lancet. 2019;394(10206):1352–63.CrossRefPubMed
21.
go back to reference Update on US regulatory review of ULTOMIRIS® in NMOSD [press release]. AstraZeneca, 6 September 2023. Update on US regulatory review of ULTOMIRIS® in NMOSD [press release]. AstraZeneca, 6 September 2023.
22.
go back to reference Pittock SJ, Barnett M, Bennett JL, et al. Ravulizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. Ann Neurol. 2023;93(6):1053–68.CrossRefPubMed Pittock SJ, Barnett M, Bennett JL, et al. Ravulizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. Ann Neurol. 2023;93(6):1053–68.CrossRefPubMed
23.
go back to reference Dias S, Ades AE, Welton NJ, Jansen JP, Sutton AJ. Generalised linear models. In: Dias S, Welton NJ, Jansen JP, Sutton AJ, editors. Network meta-analysis for decision making. Wiley; 2018. p. 93–153.CrossRef Dias S, Ades AE, Welton NJ, Jansen JP, Sutton AJ. Generalised linear models. In: Dias S, Welton NJ, Jansen JP, Sutton AJ, editors. Network meta-analysis for decision making. Wiley; 2018. p. 93–153.CrossRef
24.
go back to reference Jansen JP, Fleurence R, Devine B, et al. Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR task force on indirect treatment comparisons good research practices: part 1. Value Health. 2011;14(4):417–28.CrossRefPubMed Jansen JP, Fleurence R, Devine B, et al. Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR task force on indirect treatment comparisons good research practices: part 1. Value Health. 2011;14(4):417–28.CrossRefPubMed
25.
go back to reference Dias S, Sutton AJ, Ades AE, Welton NJ. Evidence synthesis for decision making 2: a generalized linear modeling framework for pairwise and network meta-analysis of randomized controlled trials. Med Decis Mak. 2013;33(5):607–17.CrossRef Dias S, Sutton AJ, Ades AE, Welton NJ. Evidence synthesis for decision making 2: a generalized linear modeling framework for pairwise and network meta-analysis of randomized controlled trials. Med Decis Mak. 2013;33(5):607–17.CrossRef
26.
go back to reference Hoaglin DC, Hawkins N, Jansen JP, et al. Conducting indirect-treatment-comparison and network-meta-analysis studies: report of the ISPOR task force on indirect treatment comparisons good research practices: part 2. Value Health. 2011;14(4):429–37.CrossRefPubMed Hoaglin DC, Hawkins N, Jansen JP, et al. Conducting indirect-treatment-comparison and network-meta-analysis studies: report of the ISPOR task force on indirect treatment comparisons good research practices: part 2. Value Health. 2011;14(4):429–37.CrossRefPubMed
27.
go back to reference Hutton B, Salanti G, Caldwell DM, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med. 2015;162(11):777–84.CrossRefPubMed Hutton B, Salanti G, Caldwell DM, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med. 2015;162(11):777–84.CrossRefPubMed
28.
go back to reference Rouse B, Chaimani A, Li T. Network meta-analysis: an introduction for clinicians. Intern Emerg Med. 2017;12(1):103–11.CrossRefPubMed Rouse B, Chaimani A, Li T. Network meta-analysis: an introduction for clinicians. Intern Emerg Med. 2017;12(1):103–11.CrossRefPubMed
29.
go back to reference Evrenoglou T, White IR, Afach S, Mavridis D, Chaimani A. Network meta-analysis of rare events using penalized likelihood regression. Stat Med. 2022;41(26):5203–19.CrossRefPubMedPubMedCentral Evrenoglou T, White IR, Afach S, Mavridis D, Chaimani A. Network meta-analysis of rare events using penalized likelihood regression. Stat Med. 2022;41(26):5203–19.CrossRefPubMedPubMedCentral
30.
go back to reference Heinze G, Schemper M. A solution to the problem of monotone likelihood in Cox regression. Biometrics. 2001;57(1):114–9.CrossRefPubMed Heinze G, Schemper M. A solution to the problem of monotone likelihood in Cox regression. Biometrics. 2001;57(1):114–9.CrossRefPubMed
31.
32.
go back to reference Tahara M, Oeda T, Okada K, et al. Safety and efficacy of rituximab in neuromyelitis optica spectrum disorders (RIN-1 study): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2020;19(4):298–306.CrossRefPubMed Tahara M, Oeda T, Okada K, et al. Safety and efficacy of rituximab in neuromyelitis optica spectrum disorders (RIN-1 study): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2020;19(4):298–306.CrossRefPubMed
33.
go back to reference Cree BA, Bennett JL, Kim HJ, et al. Sensitivity analysis of the primary endpoint from the N-MOmentum study of inebilizumab in NMOSD. Mult Scler. 2021;27(13):2052–61.CrossRefPubMedPubMedCentral Cree BA, Bennett JL, Kim HJ, et al. Sensitivity analysis of the primary endpoint from the N-MOmentum study of inebilizumab in NMOSD. Mult Scler. 2021;27(13):2052–61.CrossRefPubMedPubMedCentral
Metadata
Title
Network Meta-analysis of Ravulizumab and Alternative Interventions for the Treatment of Neuromyelitis Optica Spectrum Disorder
Authors
Stacey L. Clardy
Sean J. Pittock
Orhan Aktas
Jin Nakahara
Noriko Isobe
Diego Centonze
Sami Fam
Adrian Kielhorn
Jeffrey C. Yu
Jeroen Jansen
Ina Zhang
Publication date
09-05-2024
Publisher
Springer Healthcare
Published in
Neurology and Therapy / Issue 3/2024
Print ISSN: 2193-8253
Electronic ISSN: 2193-6536
DOI
https://doi.org/10.1007/s40120-024-00597-7

Keynote series | Spotlight on menopause

Menopause can have a significant impact on the body, with effects ranging beyond the endocrine and reproductive systems. Learn about the systemic effects of menopause, so you can help patients in your clinics through the transition.   

Prof. Martha Hickey
Dr. Claudia Barth
Dr. Samar El Khoudary
Developed by: Springer Medicine
Watch now

Advances in Alzheimer's

Alzheimer's research and care is changing rapidly. Keep up with the latest developments from key international conferences, together with expert insights on how to integrate these advances into practice.

This content is intended for healthcare professionals outside of the UK.

Supported by:
  • Lilly
Developed by: Springer Healthcare IME
Learn more