Comparative effectiveness in multiple sclerosis: A methodological comparison

Izanne Roos, Ibrahima Diouf, Sifat Sharmin, Dana Horakova, Eva Kubala Havrdova, Francesco Patti, Vahid Shaygannejad, Serkan Ozakbas, Guillermo Izquierdo, Sara Eichau, Marco Onofrj, Alessandra Lugaresi, Raed Alroughani, Alexandre Prat, Marc Girard, Pierre Duquette, Murat Terzi, Cavit Boz, Francois Grand’Maison, Patrizia SolaDiana Ferraro, Pierre Grammond, Recai Turkoglu, Katherine Buzzard, Olga Skibina, Bassem Yamou, Ayse Altintas, Oliver Gerlach, Vincent van Pesch, Yolanda Blanco, Davide Maimone, Jeannette Lechner-Scott, Roberto Bergamaschi, Rana Karabudak, Chris McGuigan, Elisabetta Cartechini, Michael Barnett, Stella Hughes, Maria José Sa, Claudio Solaro, Cristina Ramo-Tello, Suzanne Hodgkinson, Daniele Spitaleri, Aysun Soysal, Thor Petersen, Franco Granella, Koen de Gans, Pamela McCombe, Radek Ampapa, Bart Van Wijmeersch, Anneke van der Walt, Helmut Butzkueven, Julie Prevost, Jose Luis Sanchez-Menoyo, Guy Laureys, Riadh Gouider, Tamara Castillo-Triviño, Orla Gray, Eduardo Aguera-Morales, Abdullah Al-Asmi, Cameron Shaw, Norma Deri, Talal Al-Harbi, Yara Fragoso, Tunde Csepany, Angel Perez Sempere, Irene Trevino-Frenk, Jan Schepel, Fraser Moore, Charles Malpas, Tomas Kalincik, on behalf of the MSBase Study Group

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)


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.

Original languageEnglish
Pages (from-to)326–332
Number of pages7
JournalMultiple Sclerosis Journal
Issue number3
Publication statusPublished - Mar 2023


  • causal inference
  • multiple sclerosis
  • Observational

Cite this