Determinants of Therapeutic Lag in Multiple Sclerosis

Izanne Roos (1) , Emmanuelle Leray (2, 3) , Federico Frascoli (4) , Romain Casey (5, 6, 7) , Dana Horakova (8) , Eva Havrdova (8) , Maria Trojano , Guillermo Izquierdo Ayuso , Sara Eichau Madueno (9) , Francesco Patti , Alexandre Prat , Marc Girard , Pierre Duquette , Marco Onofrj (10) , Alessandra Lugaresi (10) , Pierre Grammond , Serkan Ozakbas , Patrizia Sola , Diana Ferraro (11) , Roberto Bergamaschi , Elisabetta Cartechini , Maria Jose Sa , Cavit Boz , Francois Grand-Maison , Jeannette Lechner-Scott , Murat Terzi , Franco Granella , Raed Alroughani , Gerardo Iuliano , Raymond Hupperts , Daniele Litterio A. Spitaleri , Vincent van Pesch , Aysun Soysal , Julie Prévost-Zuddas , Francisco Javier Olascoaga Urtaza , Eduardo Aguera-Morales , Recai Turkoglu , Mark Slee , Cristina Ramo (12) , Youssef Sidhom , Riadh Gouider , Pamela Mccombe (12) , Helmut Butzkueven (13) , Charles Malpas , Sandra Vukusic (7) , Tomas Kalincik (1)

1 University of Melbourne
2 REPERES - Recherche en Pharmaco-épidémiologie et Recours aux Soins
3 EHESP - École des Hautes Études en Santé Publique [EHESP]
4 Swinburne University of Technology [Melbourne]
5 UCBL - Université Claude Bernard Lyon 1
6 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
7 HCL - Hospices Civils de Lyon
8 UK - Univerzita Karlova [Praha, Česká republika] = Charles University [Prague, Czech Republic]
9 Unict - Università degli studi di Catania = University of Catania
10 Ud'A - Università degli studi "G. d'Annunzio" Chieti-Pescara [Chieti-Pescara]
11 UNIMORE - Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia
12 UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations] - The University of Queensland
13 Monash University [Clayton]

Objective: To explore the associations of patient and disease characteristics with the duration of therapeutic lag for relapses and disability progression.Background: Therapeutic lag represents the delay from initiation of therapy to attainment of full treatment effect. Understanding the determinants of therapeutic lag provides valuable information for personalised choice of therapy in multiple sclerosis (MS).Design/Methods: Data from MSBase, a multinational MS registry, and OFSEP, the French national registry, were used. Patients diagnosed with MS, minimum 1-year exposure to MS treatment, minimum 3-year pre-treatment follow up and yearly review were included in the analysis. By studying incidence of relapses and 6-month confirmed disability progression, the duration of therapeutic lag was calculated by identifying the first local minimum of the first derivative after treatment start in subgroups stratified by patient and disease characteristics. Pairwise analyses of univariate predictors were performed. Combinations of determinants that consistently drove differences in therapeutic lag in pair by pair analyses were included in the final model.Results: Baseline EDSS, ARR and sex were associated with duration of therapeutic lag on disability progression in univariate and pairwise bivariable analyses. In the final model, therapeutic lag was 27.8 weeks shorter in females with ARR<1 and EDSS>6 compared to those with EDSS>=6 (26.6, 18.2–34.9 vs 54.3, 47.2–61.5). Baseline EDSS, ARR, sex and MS phenotype were associated with duration of therapeutic lag on relapses in univariate analyses. Pairwise bivariable analyses of the pairs of determinants suggested ependently associated with therapeutic lag. In the final model, therapeutic lag was shortest in those with RRMS and EDSS<6 compared to the other represented groups.Conclusions: We have utilised a novel method for the quantification of therapeutic lag in different patient groups. Baseline EDSS and ARR are the most important determinants of therapeutic lag for both disability progression and relapses.

Mots clés: Multiple Sclerosis

Domaines: Sciences du Vivant [q-bio]

Izanne Roos, Emmanuelle Leray, Federico Frascoli, Romain Casey, Dana Horakova, et al.. Determinants of Therapeutic Lag in Multiple Sclerosis. Neurology, 2020, 94 (15). ⟨hal-02929410⟩