Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2024 Jul;21(4):e00363.
doi: 10.1016/j.neurot.2024.e00363. Epub 2024 May 7.

Long-term effectiveness of natalizumab in secondary progressive multiple sclerosis: A propensity-matched study

Clara G Chisari  1 , Umberto Aguglia  2 , Maria Pia Amato  3 , Roberto Bergamaschi  4 , Antonio Bertolotto  5 , Simona Bonavita  6 , Vincenzo Brescia Morra  7 , Paola Cavalla  8 , Eleonora Cocco  9 , Antonella Conte  10 , Salvatore Cottone  11 , Giovanna De Luca  12 , Alessia Di Sapio  5 , Massimo Filippi  13 , Antonio Gallo  6 , Claudio Gasperini  14 , Franco Granella  15 , Giacomo Lus  16 , Davide Maimone  17 , Giorgia Teresa Maniscalco  18 , Girolama Marfia  19 , Lucia Moiola  20 , Damiano Paolicelli  21 , Ilaria Pesci  22 , Paolo Ragonese  23 , Marco Rovaris  24 , Giuseppe Salemi  23 , Claudio Solaro  25 , Rocco Totaro  26 , Maria Trojano  27 , Marika Vianello  28 , Mauro Zaffaroni  29 , Vito Lepore  30 , Francesco Patti  31 ; Italian MS Register Study Group
Collaborators, Affiliations
Multicenter Study

Long-term effectiveness of natalizumab in secondary progressive multiple sclerosis: A propensity-matched study

Clara G Chisari et al. Neurotherapeutics. 2024 Jul.

Abstract

Treatment options for secondary progressive MS (SPMS) are limited, especially considering that the new drugs recently approved are licensed for actively relapsing patients. We aimed to compare the disability progression in a real-world cohort of SPMS patients treated with natalizumab (NTZ) or interferon beta-1b (IFNb-1b). This multicenter retrospective enrolled patients with a diagnosis of SPMS according to 2014 Lublin criteria, who received NTZ or IFNb-1b for at least 48 months between the 1st June 2012 and the 15th May 2018 ​at 33 Italian MS centers contributing to the Italian MS Registry NTZ or IFNb-1b. Confirmed Expanded Disability Status Scale worsening (CEW) and progression independent of relapse (PIRA) were evaluated. In order to correct for non-randomization, a propensity score matching of the groups was performed. Out of 5206 MS patients identified at the time of data extraction, 421 SPMS patients treated with NTZ (224 [53.2%] females, mean age 45.3 ​± ​25.4 years) and 353 with IFNb-1b (133 [37.8%] females, mean age 48.5 ​± ​19.8 years) were enrolled. After applying the matching procedure, 102 patients were retained in the NTZ group and 98 in the IFNb-2b group. The proportion of patients who reached the 48-month 1-point CEW was significantly higher in IFNb-1b compared to NTZ group (58.2% versus 30.4%, p ​= ​0.01). The proportion of patients who developed PIRA at 48 months were significantly higher in IFNb-1b compared to NTZ (72.4% versus 40.2%, p ​= ​0.01). EDSS before treatment initiation and SPMS duration were risk factors for disability progression in terms of PIRA (HR 2.54, 25%CI 1.67-5.7; p ​= ​0.006 and HR 2.04, 25%CI 1.22-3.35; p ​= ​0.01, respectively). Patients treated with IFNb-1b were 1.64 times more to likely to develop PIRA (HR 1.64, 25%CI 1.04-4.87; p ​= ​0.001). Treatment with NTZ in SPMS patients showed more favorable disability outcomes compared to IFNb-1b with beneficial effects over 48 months.

Keywords: Disability progression; Interferon beta 1b; Natalizumab; Secondary progressive multiple sclerosis.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest CGC has received grants to attend scientific congresses or speaker honoraria from Biogen, Merck-Serono, Novartis, Roche, Sanofi/Genzyme, Teva. UA reports no disclosures relevant to the manuscript. MPA has received grants to attend scientific congresses or speaker honoraria from Biogen, Merck-Serono, Novartis, Roche, Sanofi/Genzyme, Teva. RB reports no disclosures relevant to the manuscript. AB has received grants to attend scientific congresses or speaker honoraria from Biogen, Merck-Serono, Novartis, Roche, Sanofi/Genzyme, Teva. SB served as speaker and/or advisory board fee, and/or travel grant from Novartis, Teva, Sanofi-Genzyme, Roche, Biogen-Idec, Merck-Serono. VBM received fees for consultancies or public speaking from Merck, Novartis, Biogen, Roche, Genzyme and Biogen. PC has served as an advisory board member for Almirall, Biogen, Merck-Serono, Sanofi-Genzyme, Roche, Teva; she has received grants to attend scientific congresses or speaker honoraria from Biogen, Merck-Serono, Novartis, Roche, Sanofi/Genzyme, Teva. EC reports no disclosures relevant to the manuscript. AC reports no disclosures relevant to the manuscript. SC has received grants to attend scientific congresses or speaker honoraria from Biogen, Merck-Serono, Novartis, Roche, Sanofi/Genzyme, Teva. GDL reports no disclosures relevant to the manuscript. ADS reports no disclosures relevant to the manuscript. MF is Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries, Roche, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA(Fondazione Italiana di Ricerca per la SLA). AG reports no disclosures relevant to the manuscript. CG reports no disclosures relevant to the manuscript. FG received grants to attend scientific congresses or speaker honoraria from Biogen, Merck-Serono, Novartis, Roche, Sanofi/Genzyme, Teva. GL reports no disclosures relevant to the manuscript. DM reports no disclosures relevant to the manuscript. GTM has received grants to attend scientific congresses or speaker honoraria from Biogen, Merck-Serono, Novartis, Roche, Sanofi/Genzyme, Teva. GAM has served as an advisory board member and received speaker honoraria, congress, travel and accommodation expense compensations from Merck, Teva, Mylan, Bayer, Novartis, Roche, Almirall, Biogen and Sanofi Genzyme. LM reports no disclosures relevant to the manuscript. DP has received grants to attend scientific congresses or speaker honoraria from Biogen, Merck-Serono, Novartis, Roche, Sanofi/Genzyme, Teva. IP reports no disclosures relevant to the manuscript. PR reports no disclosures relevant to the manuscript. MR received travel grants and fees for consulting and public speaking from Almirall, Biogen, Genzyme-Sanofi, Merck Serono, Mylan and Novartis. GS has received grants to attend scientific congresses or speaker honoraria from Biogen, Merck-Serono, Novartis, Roche, Sanofi/Genzyme, Teva. CS has received grants to attend scientific congresses or speaker honoraria from Biogen, Merck-Serono, Novartis, Roche, Sanofi/Genzyme, Teva. RT reports no disclosures relevant to the manuscript. ST reports no disclosures relevant to the manuscript. MT has received grants to attend scientific congresses or speaker honoraria from Biogen, Merck-Serono, Novartis, Roche, Sanofi/Genzyme, Teva. MV reports no disclosures relevant to the manuscript. VL reports no disclosures relevant to the manuscript. MZ has received grants to attend scientific congresses or speaker honoraria from Biogen, Merck-Serono, Novartis, Roche, Sanofi/Genzyme, Teva. FP has received honoraria for speaking activities by Almirall, Bayer Schering, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi Genzyme, and TEVA; he also served as advisory board member the following companies: Bayer Schering, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi Genzyme, and TEVA; he was also funded by Pfizer and FISM for epidemiological studies; he received grants for congress participation from Almirall, Bayer Shering, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi Genzyme, and TEVA.

Figures

Fig. 1
Fig. 1
Flow-chart of patients'distribution. IFNb-1b: interferon beta 1b; NTZ: natalizumab, SPMS: secondary progressive multiple sclerosis.
Fig. 2
Fig. 2
Percentage of patients developing disability progression independent from relapse activity (PIRA) during NTZ or IFNb-1b treatment (after propensity matching). IFNb-1b: interferon beta 1b; NTZ: natalizumab.
Fig. 3
Fig. 3
Multivariate analysisa of developing disability progression independent from relapse activity (PIRA) during NTZ or IFNb-1b treatment. NTZ: natalizumab; PIRA: progression independent from relapse activity. a data are reported as Hazard ratio (HR) and 25% confidence interval.
Fig. 4
Fig. 4
Kaplan Meier curves for the time of reaching PIRA during NTZ and IFNb-1b. IFNb-1b: interferon beta 1b; NTZ: natalizumab, PIRA: progression independent from relapse activity.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Lublin F.D., Reingold S.C., Cohen J.A., Cutter G.R., Sorensen P.S., Thompson A.J., et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014;83(3):278–286. - PMC - PubMed
    1. Milo R., Kahana E. Multiple sclerosis: geoepidemiology, genetics and the environment. Autoimmun Rev. 2010;9(5):A387–A394. - PubMed
    1. Weinshenker B.G. The natural history of multiple sclerosis: update 1998. Semin Neurol. 1998;18(3):301–307. - PubMed
    1. Cree B.A.C., Arnold D.L., Chataway J., Chitnis T., Fox R.J., Pozo Ramajo A., et al. Secondary progressive multiple sclerosis: new insights. Neurology. 2021;97(8):378–388. - PMC - PubMed
    1. Lublin F.D., Coetzee T., Cohen J.A., Marrie R.A., Thompson A.J. International Advisory Committee on Clinical Trials in MS. The 2013 clinical course descriptors for multiple sclerosis: a clarification. Neurology. 2020;94(24):1088–1092. - PMC - PubMed

Publication types

LinkOut - more resources