Determinants of therapeutic lag in multiple sclerosis

Izanne Roos, Emmanuelle Leray, Federico Frascoli, Romain Casey, J. William L. Brown, Dana Horakova, Eva Kubala Havrdova, Marc Debouverie, Maria Trojano, Francesco Patti, Guillermo Izquierdo, Sara Eichau, Gilles Edan, Alexandre Prat, Marc Girard, Pierre Duquette, Marco Onofrj, Alessandra Lugaresi, Pierre Grammond, Jonathan CironAurélie Ruet, Serkan Ozakbas, Jérôme De Seze, Céline Louapre, Hélène Zephir, Maria José Sá, Patrizia Sola, Diana Ferraro, Pierre Labauge, Gilles Defer, Roberto Bergamaschi, Christine Lebrun-Frenay, Cavit Boz, Elisabetta Cartechini, Thibault Moreau, David Laplaud, Jeannette Lechner-Scott, Francois Grand’Maison, Oliver Gerlach, Murat Terzi, Franco Granella, Raed Alroughani, Gerardo Iuliano, Vincent Van Pesch, Bart Van Wijmeersch, Daniele L.A. Spitaleri, Aysun Soysal, Eric Berger, Julie Prevost, Eduardo Aguera-Morales, Pamela McCombe, Tamara Castillo Triviño, Pierre Clavelou, Jean Pelletier, Recai Turkoglu, Bruno Stankoff, Olivier Gout, Eric Thouvenot, Olivier Heinzlef, Youssef Sidhom, Riadh Gouider, Tunde Csepany, Bertrand Bourre, Abdullatif Al Khedr, Olivier Casez, Philippe Cabre, Alexis Montcuquet, Abir Wahab, Jean Philippe Camdessanche, Aude Maurousset, Ivania Patry, Karolina Hankiewicz, Corinne Pottier, Nicolas Maubeuge, Céline Labeyrie, Chantal Nifle, Alasdair Coles, Charles B. Malpas, Sandra Vukusic, Helmut Butzkueven, Tomas Kalincik, on behalf of the MSBase and OFSEP study groups

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Background: A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups. Objectives: The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation. Methods: Data from MSBase, a multinational multiple sclerosis (MS) registry, and OFSEP, the French MS registry, were used. Patients diagnosed with MS, minimum 1 year of exposure to MS treatment and 3 years of pre-treatment follow-up, were included in the analysis. Studied outcomes were incidence of relapses and disability accumulation. Therapeutic lag was calculated using an objective, validated method in subgroups stratified by patient and disease characteristics. Therapeutic lag under specific circumstances was then estimated in subgroups defined by combinations of clinical and demographic determinants. Results: High baseline disability scores, annualised relapse rate (ARR) ⩾ 1 and male sex were associated with longer therapeutic lag on disability progression in sufficiently populated groups: females with expanded disability status scale (EDSS) < 6 and ARR < 1 had mean lag of 26.6 weeks (95% CI = 18.2–34.9), males with EDSS < 6 and ARR < 1 31.0 weeks (95% CI = 25.3–36.8), females with EDSS < 6 and ARR ⩾ 1 44.8 weeks (95% CI = 24.5–65.1), and females with EDSS ⩾ 6 and ARR < 1 54.3 weeks (95% CI = 47.2–61.5). Conclusions: Pre-treatment EDSS and ARR are the most important determinants of therapeutic lag.

Original languageEnglish
Pages (from-to)1838-1851
Number of pages14
JournalMultiple Sclerosis Journal
Issue number12
Publication statusPublished - Oct 2021


  • multiple sclerosis
  • Neurology
  • observational study
  • therapeutic lag

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