Comparative effectiveness in multiple sclerosis: A methodological comparison
Izanne Roos 1, Ibrahima Diouf 2, Sifat Sharmin 2, Dana Horakova 3, Eva Kubala Havrdova 3, Francesco Patti 4, Vahid Shaygannejad 5, Serkan Ozakbas 6, Guillermo Izquierdo 7, Sara Eichau 7, Marco Onofrj 8, Alessandra Lugaresi 9, Raed Alroughani 10, Alexandre Prat 11, Marc Girard 11, Pierre Duquette 11, Murat Terzi 12, Cavit Boz 13, Francois Grand'Maison 14, Patrizia Sola 15, Diana Ferraro 15, Pierre Grammond 16, Recai Turkoglu 17, Katherine Buzzard 18, Olga Skibina 19, Bassem Yamou 20, Ayse Altintas 21, Oliver Gerlach 22, Vincent van Pesch 23, Yolanda Blanco 24, Davide Maimone 25, Jeannette Lechner-Scott 26, Roberto Bergamaschi 27, Rana Karabudak 28, Chris McGuigan 29, Elisabetta Cartechini 30, Michael Barnett 31, Stella Hughes 32, Maria José Sa 33, Claudio Solaro 34, Cristina Ramo-Tello 35, Suzanne Hodgkinson 36, Daniele Spitaleri 37, Aysun Soysal 38, Thor Petersen 39, Franco Granella 40, Koen de Gans 41, Pamela McCombe 42, Radek Ampapa 43, Bart Van Wijmeersch 44, Anneke van der Walt 45, Helmut Butzkueven 45, Julie Prevost 46, Jose Luis Sanchez-Menoyo 47, Guy Laureys 48, Riadh Gouider 49, Tamara Castillo-Triviño 50, Orla Gray 51, Eduardo Aguera-Morales 52, Abdullah Al-Asmi 53, Cameron Shaw 54, Norma Deri 55, Talal Al-Harbi 56, Yara Fragoso 57, Tunde Csepany 58, Angel Perez Sempere 59, Irene Trevino-Frenk 60, Jan Schepel 61, Fraser Moore 62, Charles Malpas 1, Tomas Kalincik 1
Affiliations
Affiliations
- 1CORe, Department of Medicine, University of Melbourne, Melbourne, VIC, Australia/Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia.
- 2CORe, Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.
- 3Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic.
- 4Department of Medical and Surgical Sciences and Advanced Technologies, G.F. Ingrassia, Catania, Italy/Multiple Sclerosis Center, University of Catania, Catania, Italy.
- 5Isfahan University of Medical Sciences, Isfahan, Iran.
- 6Dokuz Eylul University, İzmir, Turkey.
- 7Hospital Universitario Virgen Macarena, Sevilla, Spain.
- 8University G. d'Annunzio, Chieti, Italy.
- 9Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy/IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
- 10Division of Neurology, Department of Medicine, Amiri Hospital, Sharq, Kuwait.
- 11CHUM MS Center and Universite de Montreal, Montreal, QC, Canada.
- 1219 Mayis University, Samsun, Turkey.
- 13KTU Medical Faculty Farabi Hospital, Trabzon, Turkey.
- 14Neuro Rive-Sud, Greenfield Park, QC, Canada.
- 15Department of Neuroscience, Azienda Ospedaliera Universitaria, Modena, Italy.
- 16CISSS Chaudière-Appalache, Levis, QC, Canada.
- 17Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey.
- 18Department of Neurology, Box Hill Hospital, Melbourne, VIC, Australia/Monash University, Melbourne, VIC, Australia/Neuroimmunology Centre, Royal Melbourne Hospital, Melbourne, VIC, Australia.
- 19Department of Neurology, Box Hill Hospital, Melbourne, VIC, Australia/The Alfred Hospital, Melbourne, VIC, Australia.
- 20Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut, Lebanon.
- 21Department of Neurology, School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey.
- 22Zuyderland Medical Center, Sittard-Geleen, The Netherlands/School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
- 23Cliniques Universitaires Saint-Luc, Brussels, Belgium/Université Catholique de Louvain, Ottignies-Louvain-la-Neuve, Belgium.
- 24Center of Neuroimmunology, Service of Neurology, Hospital Clinic de Barcelona, Barcelona, Spain.
- 25Centro Sclerosi Multipla, UOC Neurologia, ARNAS Garibaldi, Catania, Italy.
- 26School of Medicine and Public Health, University Newcastle, Newcastle, NSW, Australia/Department of Neurology, John Hunter Hospital, Hunter New England Health, Newcastle, NSW, Australia.
- 27IRCCS Mondino Foundation, Pavia, Italy.
- 28Hacettepe University, Ankara, Turkey.
- 29St. Vincent's University Hospital, Dublin, Ireland.
- 30UOC Neurologia, Azienda Sanitaria Unica Regionale Marche-AV3, Macerata, Italy.
- 31Brain and Mind Centre, Sydney, NSW, Australia.
- 32Royal Victoria Hospital, Belfast, UK.
- 33Department of Neurology, Centro Hospitalar Universitario de Sao Joao, Porto, Portugal.
- 34Department of Neurology, ASL3 Genovese, Genova, Italy/Department of Rehabilitation, M.L. Novarese Hospital Moncrivello, Moncrivello, Italy.
- 35Hospital Germans Trias i Pujol, Badalona, Spain.
- 36Immune Tolerance Laboratory, Ingham Institute and Department of Medicine, University of New South Wales, Sydney, NSW, Australia.
- 37Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino, Avellino, Italy.
- 38Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases, Istanbul, Turkey.
- 39Aarhus University Hospital, Aarhus, Denmark.
- 40Department of Medicine and Surgery, University of Parma, Parma, Italy/Department of Emergency and General Medicine, Parma University Hospital, Parma, Italy.
- 41Groene Hart Ziekenhuis, Gouda, The Netherlands.
- 42The University of Queensland, Brisbane, QLD, Australia/Royal Brisbane and Women's Hospital, Herston, QLD, Australia.
- 43Nemocnice Jihlava, Jihlava, Czech Republic.
- 44Rehabilitation & MS Centre, University MS Centre, Noorderhart Hospital, Pelt, Belgium/Pelt and Hasselt University, Hasselt, Belgium.
- 45Department of Neurology, The Alfred Hospital, Melbourne, VIC, Australia/Central Clinical School, Monash University, Clayton, VIC, Australia.
- 46CSSS Saint-Jérôme, Saint-Jerome, QC, Canada.
- 47Hospital de Galdakao-Usansolo, Galdakao, Spain.
- 48Department of Neurology, University Hospital Ghent, Ghent, Belgium.
- 49Department of Neurology, Razi Hospital, Manouba, Tunisia.
- 50Hospital Universitario Donostia and IIS Biodonostia, San Sebastián, Spain.
- 51South Eastern HSC Trust, Belfast, UK.
- 52University Hospital Reina Sofia, Cordoba, Spain.
- 53Department of Medicine, Sultan Qaboos University Hospital, Al-Khodh, Oman.
- 54Geelong Hospital, Geelong, VIC, Australia.
- 55Hospital Fernandez, Capital Federal, Buenos Aires, Argentina.
- 56Neurology Department, King Fahad Specialist Hospital-Dammam, Khobar, Saudi Arabia.
- 57Universidade Metropolitana de Santos, Santos, Brazil.
- 58Department of Neurology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
- 59Hospital General Universitario de Alicante, Alicante, Spain.
- 60Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
- 61Waikato Hospital, Hamilton, New Zealand.
- 62Jewish General Hospital, Montreal, QC, Canada.
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.
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