Comparative effectiveness in multiple sclerosis: A methodological comparison
Authors: Roos Izanne , Diouf Ibrahima , Sharmin Sifat , Horakova Dana , Havrdova Eva Kubala , Patti Francesco , Shaygannejad Vahid , Ozakbas Serkan , Izquierdo Guillermo , Eichau Sara , Onofrj Marco , Lugaresi Alessandra , Alroughani Raed , Prat Alexandre , Girard Marc , Duquette Pierre , Terzi Murat , Boz Cavit , Grand’Maison Francois , Sola Patrizia , Ferraro Diana , Grammond Pierre , Turkoglu Recai , Buzzard Katherine , Skibina Olga , Yamou Bassem , Altintas Ayse , Gerlach Oliver , van Pesch Vincent , Blanco Yolanda , Maimone Davide , Lechner-Scott Jeannette , Bergamaschi Roberto , Karabudak Rana , McGuigan Chris , Cartechini Elisabetta , Barnett Michael , Hughes Stella , Sa Maria José , Solaro Claudio , Ramo-Tello Cristina , Hodgkinson Suzanne , Spitaleri Daniele , Soysal Aysun , Petersen Thor , Granella Franco , de Gans Koen , McCombe Pamela , Ampapa Radek , Van Wijmeersch Bart , van der Walt Anneke , Butzkueven Helmut , Prevost Julie , Sanchez-Menoyo Jose Luis , Laureys Guy , Gouider Riadh , Castillo-Triviño Tamara , Gray Orla , Aguera-Morales Eduardo , Al-Asmi Abdullah , Shaw Cameron , Deri Norma , Al-Harbi Talal , Fragoso Yara , Csepany Tunde , Sempere Angel Perez , Trevino-Frenk Irene , Schepel Jan , Moore Fraser , Malpas Charles , Kalincik Tomas 
Published: February 2023

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.