Comparative effectiveness in multiple sclerosis: A methodological comparison

Izanne Roos 1Ibrahima Diouf 2Sifat Sharmin 2Dana Horakova 3Eva Kubala Havrdova 3Francesco Patti 4Vahid Shaygannejad 5Serkan Ozakbas 6Guillermo Izquierdo 7Sara Eichau 7Marco Onofrj 8Alessandra Lugaresi 9Raed Alroughani 10Alexandre Prat 11Marc Girard 11Pierre Duquette 11Murat Terzi 12Cavit Boz 13Francois Grand'Maison 14Patrizia Sola 15Diana Ferraro 15Pierre Grammond 16Recai Turkoglu 17Katherine Buzzard 18Olga Skibina 19Bassem Yamou 20Ayse Altintas 21Oliver Gerlach 22Vincent van Pesch 23Yolanda Blanco 24Davide Maimone 25Jeannette Lechner-Scott 26Roberto Bergamaschi 27Rana Karabudak 28Chris McGuigan 29Elisabetta Cartechini 30Michael Barnett 31Stella Hughes 32Maria José Sa 33Claudio Solaro 34Cristina Ramo-Tello 35Suzanne Hodgkinson 36Daniele Spitaleri 37Aysun Soysal 38Thor Petersen 39Franco Granella 40Koen de Gans 41Pamela McCombe 42Radek Ampapa 43Bart Van Wijmeersch 44Anneke van der Walt 45Helmut Butzkueven 45Julie Prevost 46Jose Luis Sanchez-Menoyo 47Guy Laureys 48Riadh Gouider 49Tamara Castillo-Triviño 50Orla Gray 51Eduardo Aguera-Morales 52Abdullah Al-Asmi 53Cameron Shaw 54Norma Deri 55Talal Al-Harbi 56Yara Fragoso 57Tunde Csepany 58Angel Perez Sempere 59Irene Trevino-Frenk 60Jan Schepel 61Fraser Moore 62Charles Malpas 1Tomas Kalincik 1

Affiliations

03 January 2023

-

doi: 10.1177/13524585231151394


Abstract

Background: In the absence of evidence from randomised controlled trials, observational data can be used to emulate clinical trials and guide clinical decisions. Observational studies are, however, susceptible to confounding and bias. Among the used techniques to reduce indication bias are propensity score matching and marginal structural models.

Objective: To use the comparative effectiveness of fingolimod vs natalizumab to compare the results obtained with propensity score matching and marginal structural models.

Methods: Patients with clinically isolated syndrome or relapsing remitting MS who were treated with either fingolimod or natalizumab were identified in the MSBase registry. Patients were propensity score matched, and inverse probability of treatment weighted at six monthly intervals, using the following variables: age, sex, disability, MS duration, MS course, prior relapses, and prior therapies. Studied outcomes were cumulative hazard of relapse, disability accumulation, and disability improvement.

Results: 4608 patients (1659 natalizumab, 2949 fingolimod) fulfilled inclusion criteria, and were propensity score matched or repeatedly reweighed with marginal structural models. Natalizumab treatment was associated with a lower probability of relapse (PS matching: HR 0.67 [95% CI 0.62-0.80]; marginal structural model: 0.71 [0.62-0.80]), and higher probability of disability improvement (PS matching: 1.21 [1.02 -1.43]; marginal structural model 1.43 1.19 -1.72]). There was no evidence of a difference in the magnitude of effect between the two methods.

Conclusions: The relative effectiveness of two therapies can be efficiently compared by either marginal structural models or propensity score matching when applied in clearly defined clinical contexts and in sufficiently powered cohorts.

Keywords: Observational; causal inference; multiple sclerosis.


Similar articles

Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study.

Kalincik T, Brown JWL, Robertson N, Willis M, Scolding N, Rice CM, Wilkins A, Pearson O, Ziemssen T, Hutchinson M, McGuigan C, Jokubaitis V, Spelman T, Horakova D, Havrdova E, Trojano M, Izquierdo G, Lugaresi A, Prat A, Girard M, Duquette P, Grammond P, Alroughani R, Pucci E, Sola P, Hupperts R, Lechner-Scott J, Terzi M, Van Pesch V, Rozsa C, Grand'Maison F, Boz C, Granella F, Slee M, Spitaleri D, Olascoaga J, Bergamaschi R, Verheul F, Vucic S, McCombe P, Hodgkinson S, Sanchez-Menoyo JL, Ampapa R, Simo M, Csepany T, Ramo C, Cristiano E, Barnett M, Butzkueven H, Coles A; MSBase Study Group.Lancet Neurol. 2017 Apr;16(4):271-281. doi: 10.1016/S1474-4422(17)30007-8. Epub 2017 Feb 11.PMID: 28209331

The comparative effectiveness of fingolimod, natalizumab, and ocrelizumab in relapsing-remitting multiple sclerosis.

Boz C, Ozakbas S, Terzi M, Karabudak R, Sevim S, Turkoglu R, Soysal A, Balcı BP, Efendi H, Turan ÖF, Yüceyar N, Yetkin MF, Karahan SZ, Demirkıran M, Guler S, Agan K, Kıylıoğlu N, Baba C, Tuncer A, Köseoğlu M.Neurol Sci. 2023 Jun;44(6):2121-2129. doi: 10.1007/s10072-023-06608-z. Epub 2023 Jan 23.PMID: 36689010

Natalizumab Versus Fingolimod in Patients with Relapsing-Remitting Multiple Sclerosis: A Subgroup Analysis From Three International Cohorts.

Sharmin S, Lefort M, Andersen JB, Leray E, Horakova D, Havrdova EK, Alroughani R, Izquierdo G, 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, Prevost J, Maimone D, Skibina O, Buzzard K, Van der Walt A, Van Wijmeersch B, Csepany T, Spitaleri D, Vucic S, Casey R, Debouverie M, Edan G, Ciron J, Ruet A, De Sèze J, Maillart E, Zephir H, Labauge P, Defer G, Lebrun-Frénay 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, Camdessanché JP, Maurousset A, Patry I, Hankiewicz K, Pottier C, Maubeuge N, Labeyrie C, Nifle C, Laplaud D, Koch-Henriksen N, Sellebjerg FT, Soerensen PS, Pfleger CC, Rasmussen PV, Jensen MB, Frederiksen JL, Bramow S, Mathiesen HK, Schreiber KI, Magyari M, Vukusic S, Butzkueven H, Kalincik T; Danish Multiple Sclerosis Registry, OFSEP and the MSBase investigators.CNS Drugs. 2021 Nov;35(11):1217-1232. doi: 10.1007/s40263-021-00860-7. Epub 2021 Sep 18.PMID: 34536228

Systematic literature review and network meta-analysis in highly active relapsing-remitting multiple sclerosis and rapidly evolving severe multiple sclerosis.

Huisman E, Papadimitropoulou K, Jarrett J, Bending M, Firth Z, Allen F, Adlard N.BMJ Open. 2017 Mar 10;7(3):e013430. doi: 10.1136/bmjopen-2016-013430.PMID: 28283486 Free PMC article. Review.

Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis.

Tramacere I, Del Giovane C, Salanti G, D'Amico R, Filippini G.Cochrane Database Syst Rev. 2015 Sep 18;2015(9):CD011381. doi: 10.1002/14651858.CD011381.pub2.PMID: 26384035 Free PMC article. Review.


KMEL References