Background: Natalizumab and fingolimod were the first preparations recommended for disease breakthrough in priorly treated relapsing-remitting multiple sclerosis. Of three published head-to-head studies two showed that natalizumab is the more effective to prevent relapses and EDSS worsening. Methods: By re-analyzing original published results from MSBase, France, and Denmark using uniform methodologies, we aimed at identifying the effects of differences in methodology, in the MS-populations, and at re-evaluating the differences in effectiveness between the two drugs. We gained access to copies of the individual amended databases and pooled all data. We used uniform inclusion/exclusion criteria and statistical methods with Inverse Probability Treatment Weighting. Results: The pooled analyses comprised 968 natalizumab- and 1479 fingolimod treated patients. The on-treatment natalizumab/fingolimod relapse rate ratio was 0.77 (p=0.004). The hazard ratio (HR) for a first relapse was 0.82 (p=0.030), and the HR for sustained EDSS improvement was 1.4 (p=0.009). There were modest differences between each of the original published studies and the replication study, but the conclusions of the three original studies remained unchanged: in two of them natalizumab was more effective, but in the third there was no difference between natalizumab and fingolimod. Conclusion: The results were largely invariant to the epidemiological and statistical methods but differed between the MS populations. Generally, the advantage of natalizumab was confirmed.

The effectiveness of natalizumab vs fingolimod–A comparison of international registry studies / Andersen, J. B.; Sharmin, S.; Lefort, M.; Koch-Henriksen, N.; Sellebjerg, F.; Sorensen, P. S.; Hilt Christensen, C. C.; Rasmussen, P. V.; Jensen, M. B.; Frederiksen, J. L.; Bramow, S.; Mathiesen, H. K.; Schreiber, K. I.; Horakova, D.; Havrdova, E. K.; Alroughani, R.; Izquierdo, G.; Eichau, S.; Ozakbas, S.; Patti, F.; Onofrj, M.; Lugaresi, A.; Terzi, M.; Grammond, P.; Grand Maison, F.; Yamout, B.; Prat, A.; Girard, M.; Duquette, P.; Boz, C.; Trojano, M.; Mccombe, P.; Slee, M.; Lechner-Scott, J.; Turkoglu, R.; Sola, P.; Ferraro, D.; Granella, F.; Shaygannejad, V.; Prevost, J.; Skibina, O.; Solaro, C.; Karabudak, R.; Wijmeersch, B. V.; Csepany, T.; Spitaleri, D.; Vucic, S.; Casey, R.; Debouverie, M.; Edan, G.; Ciron, J.; Ruet, A.; Seze, J. D.; Maillart, E.; Zephir, H.; Labauge, P.; Defer, G.; Lebrun, C.; Moreau, T.; Berger, E.; Clavelou, P.; Pelletier, J.; Stankoff, B.; Gout, O.; Thouvenot, E.; Heinzlef, O.; Al-Khedr, A.; Bourre, B.; Casez, O.; Cabre, P.; Montcuquet, A.; Wahab, A.; Camdessanche, J. -P.; Marousset, A.; Patry, I.; Hankiewicz, K.; Pottier, C.; Maubeuge, N.; Labeyrie, C.; Nifle, C.; Leray, E.; Laplaud, D. A.; Butzkueven, H.; Kalincik, T.; Vukusic, S.; Magyari, M.. - In: MULTIPLE SCLEROSIS AND RELATED DISORDERS. - ISSN 2211-0348. - 53:(2021), pp. 103012-103012. [10.1016/j.msard.2021.103012]

The effectiveness of natalizumab vs fingolimod–A comparison of international registry studies

Ferraro D.;
2021

Abstract

Background: Natalizumab and fingolimod were the first preparations recommended for disease breakthrough in priorly treated relapsing-remitting multiple sclerosis. Of three published head-to-head studies two showed that natalizumab is the more effective to prevent relapses and EDSS worsening. Methods: By re-analyzing original published results from MSBase, France, and Denmark using uniform methodologies, we aimed at identifying the effects of differences in methodology, in the MS-populations, and at re-evaluating the differences in effectiveness between the two drugs. We gained access to copies of the individual amended databases and pooled all data. We used uniform inclusion/exclusion criteria and statistical methods with Inverse Probability Treatment Weighting. Results: The pooled analyses comprised 968 natalizumab- and 1479 fingolimod treated patients. The on-treatment natalizumab/fingolimod relapse rate ratio was 0.77 (p=0.004). The hazard ratio (HR) for a first relapse was 0.82 (p=0.030), and the HR for sustained EDSS improvement was 1.4 (p=0.009). There were modest differences between each of the original published studies and the replication study, but the conclusions of the three original studies remained unchanged: in two of them natalizumab was more effective, but in the third there was no difference between natalizumab and fingolimod. Conclusion: The results were largely invariant to the epidemiological and statistical methods but differed between the MS populations. Generally, the advantage of natalizumab was confirmed.
2021
53
103012
103012
The effectiveness of natalizumab vs fingolimod–A comparison of international registry studies / Andersen, J. B.; Sharmin, S.; Lefort, M.; Koch-Henriksen, N.; Sellebjerg, F.; Sorensen, P. S.; Hilt Christensen, C. C.; Rasmussen, P. V.; Jensen, M. B.; Frederiksen, J. L.; Bramow, S.; Mathiesen, H. K.; Schreiber, K. I.; Horakova, D.; Havrdova, E. K.; Alroughani, R.; Izquierdo, G.; Eichau, S.; Ozakbas, S.; Patti, F.; Onofrj, M.; Lugaresi, A.; Terzi, M.; Grammond, P.; Grand Maison, F.; Yamout, B.; Prat, A.; Girard, M.; Duquette, P.; Boz, C.; Trojano, M.; Mccombe, P.; Slee, M.; Lechner-Scott, J.; Turkoglu, R.; Sola, P.; Ferraro, D.; Granella, F.; Shaygannejad, V.; Prevost, J.; Skibina, O.; Solaro, C.; Karabudak, R.; Wijmeersch, B. V.; Csepany, T.; Spitaleri, D.; Vucic, S.; Casey, R.; Debouverie, M.; Edan, G.; Ciron, J.; Ruet, A.; Seze, J. D.; Maillart, E.; Zephir, H.; Labauge, P.; Defer, G.; Lebrun, C.; Moreau, T.; Berger, E.; Clavelou, P.; Pelletier, J.; Stankoff, B.; Gout, O.; Thouvenot, E.; Heinzlef, O.; Al-Khedr, A.; Bourre, B.; Casez, O.; Cabre, P.; Montcuquet, A.; Wahab, A.; Camdessanche, J. -P.; Marousset, A.; Patry, I.; Hankiewicz, K.; Pottier, C.; Maubeuge, N.; Labeyrie, C.; Nifle, C.; Leray, E.; Laplaud, D. A.; Butzkueven, H.; Kalincik, T.; Vukusic, S.; Magyari, M.. - In: MULTIPLE SCLEROSIS AND RELATED DISORDERS. - ISSN 2211-0348. - 53:(2021), pp. 103012-103012. [10.1016/j.msard.2021.103012]
Andersen, J. B.; Sharmin, S.; Lefort, M.; Koch-Henriksen, N.; Sellebjerg, F.; Sorensen, P. S.; Hilt Christensen, C. C.; Rasmussen, P. V.; Jensen, M. B.; Frederiksen, J. L.; Bramow, S.; Mathiesen, H. K.; Schreiber, K. I.; Horakova, D.; Havrdova, E. K.; Alroughani, R.; Izquierdo, G.; Eichau, S.; Ozakbas, S.; Patti, F.; Onofrj, M.; Lugaresi, A.; Terzi, M.; Grammond, P.; Grand Maison, F.; Yamout, B.; Prat, A.; Girard, M.; Duquette, P.; Boz, C.; Trojano, M.; Mccombe, P.; Slee, M.; Lechner-Scott, J.; Turkoglu, R.; Sola, P.; Ferraro, D.; Granella, F.; Shaygannejad, V.; Prevost, J.; Skibina, O.; Solaro, C.; Karabudak, R.; Wijmeersch, B. V.; Csepany, T.; Spitaleri, D.; Vucic, S.; Casey, R.; Debouverie, M.; Edan, G.; Ciron, J.; Ruet, A.; Seze, J. D.; Maillart, E.; Zephir, H.; Labauge, P.; Defer, G.; Lebrun, C.; Moreau, T.; Berger, E.; Clavelou, P.; Pelletier, J.; Stankoff, B.; Gout, O.; Thouvenot, E.; Heinzlef, O.; Al-Khedr, A.; Bourre, B.; Casez, O.; Cabre, P.; Montcuquet, A.; Wahab, A.; Camdessanche, J. -P.; Marousset, A.; Patry, I.; Hankiewicz, K.; Pottier, C.; Maubeuge, N.; Labeyrie, C.; Nifle, C.; Leray, E.; Laplaud, D. A.; Butzkueven, H.; Kalincik, T.; Vukusic, S.; Magyari, M.
File in questo prodotto:
File Dimensione Formato  
Andersen_2021.pdf

Open access

Tipologia: Versione pubblicata dall'editore
Dimensione 1.67 MB
Formato Adobe PDF
1.67 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1251078
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 8
  • ???jsp.display-item.citation.isi??? 6
social impact