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Multiple sclerosis
Original research
Assessing treatment response to oral drugs for multiple sclerosis in real-world setting: a MAGNIMS Study
  1. Serena Ruggieri1,2,
  2. Luca Prosperini1,
  3. Sarmad Al-Araji3,
  4. Pietro Osvaldo Annovazzi4,
  5. Alvino Bisecco5,
  6. Olga Ciccarelli3,6,
  7. Nicola De Stefano7,
  8. Massimo Filippi8,9,
  9. Vinzenz Fleischer10,
  10. Nikos Evangelou11,12,
  11. Christian Enzinger13,14,
  12. Antonio Gallo5,
  13. Afagh Garjani11,12,
  14. Sergiu Groppa10,
  15. Shalom Haggiag1,
  16. Michael Khalil13,
  17. Matteo Lucchini15,16,
  18. Massimiliano Mirabella15,16,
  19. Xavier Montalban17,
  20. Carlo Pozzilli2,
  21. Paolo Preziosa8,9,
  22. Jordi Río17,
  23. Maria A Rocca8,9,
  24. Alex Rovira18,
  25. Maria L Stromillo7,
  26. Mauro Zaffaroni4,
  27. Carla Tortorella1,
  28. Claudio Gasperini1
  29. MAGNIMS Study Group
    1. 1 Department of Neurosciences, San Camillo Forlanini Hospital, Rome, Italy
    2. 2 Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy
    3. 3 Department of Neuroinflammation, Queen Square MS Centre, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK
    4. 4 Neuroimmunology Unit-Multiple Sclerosis Center, Hospital of Gallarate, ASST della Valle Olona, Gallarate, Italy
    5. 5 Department of Advanced Medical and Surgical Sciences, University of Campania 'Luigi Vanvitelli', Naples, Italy
    6. 6 National Institute for Health Research Biomedical Research Centre, University College London Hospitals, London, UK
    7. 7 Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
    8. 8 Neurology Unit and Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
    9. 9 Vita-Salute San Raffaele University, Milan, Italy
    10. 10 Department of Neurology and Neuroimaging Center (NIC) of the Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg University, Mainz, Germany
    11. 11 Mental Health & Clinical Neuroscience Unit, University of Nottingham, Nottingham, UK
    12. 12 Department of Neurology, Nottingham University Hospitals NHS Trust, Nottingham, UK
    13. 13 Department of Neurology, Medical University of Graz, Graz, Austria
    14. 14 Department of Radiology (Division of Neuroradiology, Vascular and Interventional Radiology), Medical University of Graz, Graz, Austria
    15. 15 Multiple Sclerosis Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
    16. 16 Centro di ricerca Sclerosi Multipla (CERSM), Università Cattolica del Sacro Cuore, Rome, Italy
    17. 17 Centre d'Esclerosi Multiple de Catalunya (Cemcat), Department of Neurology/Neuroimmunology, Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona, Spain
    18. 18 Section of Neuroradiology, Department of Radiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
    1. Correspondence to Dr Claudio Gasperini, Department of Neurosciences, San Camillo Forlanini Hospital, Rome 00152, Italy; c.gasperini{at}libero.it

    Abstract

    Background The assessment of treatment response is a crucial step for patients with relapsing-remitting multiple sclerosis on disease-modifying therapies (DMTs). We explored whether a scoring system developed within the MAGNIMS (MRI in Multiple Sclerosis) network to evaluate treatment response to injectable drugs can be adopted also to oral DMTs.

    Methods A multicentre dataset of 1200 patients who started three oral DMTs (fingolimod, teriflunomide and dimethyl fumarate) was collected within the MAGNIMS network. Disease activity after the first year was classified by the ‘MAGNIMS’ score based on the combination of relapses (0–≥2) and/or new T2 lesions (<3 or ≥3) on brain MRI. We explored the association of this score with the following 3-year outcomes: (1) confirmed disability worsening (CDW); (2) treatment failure (TFL); (3) relapse count between years 1 and 3. The additional value of contrast-enhancing lesions (CELs) and lesion location was explored.

    Results At 3 years, 160 patients experienced CDW: 12% of them scored ‘0’ (reference), 18% scored ‘1’ (HR=1.82, 95% CI 1.20 to 2.76, p=0.005) and 37% scored ‘2’ (HR=2.74, 95% CI 1.41 to 5.36, p=0.003) at 1 year. The analysis of other outcomes provided similar findings. Considering the location of new T2 lesions (supratentorial vs infratentorial/spinal cord) and the presence of CELs improved the prediction of CDW and TFL, respectively, in patients with minimal MRI activity alone (one or two new T2 lesions).

    Conclusions Early relapses and substantial MRI activity in the first year of treatment are associated with worse short-term outcomes in patients treated with some of the oral DMTs.

    • MRI
    • MULTIPLE SCLEROSIS
    • CLINICAL NEUROLOGY

    Data availability statement

    Data are available upon reasonable request. The data that support the findings of this study are available from the corresponding author, CG, upon reasonable request.

    https://doi.org/10.1136/jnnp-2023-331920

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      Data availability statement

      Data are available upon reasonable request. The data that support the findings of this study are available from the corresponding author, CG, upon reasonable request.

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      Footnotes

      • Twitter @paolopreziosa

      • Collaborators The MAGNIMS Study Group (https://www.magnims.eu) is a group of European clinicians and scientists with an interest in undertaking collaborative studies using MRI methods in multiple sclerosis, independent of any other organisation, and is run by a Steering Committee whose members are FB (Amsterdam, London), OC (London), NDS (Siena), CE (Graz), MF (Milan), CG (Rome), LK (Basel), JP (Oxford), MAR (Milan, co-chair), ÀR (Barcelona), JSG (Barcelona, co-chair), HV (Amsterdam) and TY (London). Steering Committee members: FB (Amsterdam UMC, Amsterdam, the Netherlands and University College London, London, UK, collaborator/Steering Committee member); OC (University College London, UK, author/collaborator/Steering Committee member); NDS (University of Siena, Italy, author/collaborator/ Steering Committee member); CE (Medical University Graz, Austria, author/collaborator/Steering Committee member); MF (San Raffaele, Milan, Italy, author/collaborator/Steering Committee member); CG (San Camillo-Forlanini Hospital, Rome, Italy, author/collaborator/co-investigator/Steering Committee member); LK (University Hospital, Basel, Switzerland, collaborator/Steering Committee member); JP (University of Oxford, UK, collaborator/Steering Committee member); MAR (co-chair) (San Raffaele, Milan, Italy, author/collaborator/Steering Committee member); ÀR (Vall d’Hebron Hospital, Barcelona, Spain, author/collaborator/Steering Committee member); JSG (co-chair) (Vall d’Hebron Hospital, Barcelona, Spain, collaborator/Steering Committee member); HV (Amsterdam UMC, Amsterdam, the Netherlands, collaborator/Steering Committee member); TY (University College London, UK, collaborator/Steering Committee member).

      • Contributors Concept and design—SR, LP, CT and CG. Acquisition, analysis or interpretation of data—SR, LP, SA-A, POA, AB, OC, NDS, MF, VF, NE, AG, SG, SH, MK, ML, MM, XM, CP, PP, JR, MAR, AR, MLS, MZ, CT and CG. Drafting of the manuscript—SR, LP, CT and CG. Critical revision of the manuscript for important intellectual content—all authors and contributors. Statistical analysis—LP. Guarantor—CG. The members of the MAGNIMS Study Group Steering Committee have reviewed, revised and approved the submitted paper.

      • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

      • Competing interests SR has received honoraria from Biogen, MS, Novartis and Teva for consulting services, speaking and/or travel support. LP has received consulting fees from Biogen, Novartis and Roche; speaker honoraria from Biogen, Genzyme, Merck Serono, Novartis and Teva; travel grants from Biogen, Genzyme, Novartis and Teva; research grants from the Italian MS Society (Associazione Italiana Sclerosi Multipla) and Genzyme. SA-A reports no disclosure relevant to the manuscript. POA received honoraria for lecturing and participation in advisory boards, and/or travel expenses for attending congresses and meetings from Almirall, Biogen, BMS-Celgene, Janssen, Merck, Mylan, Novartis, Roche Sanofi-Genzyme and Teva. AB received speaker honoraria and/or compensation for consulting service and/or speaking activities from Biogen, Roche, Merck, Celgene and Genzyme. OC receives research grant support from the Multiple Sclerosis Society of Great Britain and Northern Ireland, the NIHR and the NIHR UCLH Biomedical Research Centre. She is the Deputy Editor of Neurology, for which she receives an honorarium. NDS has received honoraria from Biogen-Idec, Bristol Myers Squibb, Celgene, Genzyme, Immunic, Merck Serono, Novartis, Roche and Teva for consulting services and speaking; serves on advisory boards for Merck, Novartis, Biogen-Idec, Roche, Genzyme and Immunic; has received research grant support from the Italian MS Society. MF is Editor-in-Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, Neurological Sciences, and Radiology; received compensation for consulting services from Alexion, Almirall, Biogen, Merck, Novartis, Roche and Sanofi; speaking activities from Bayer, Biogen, Celgene, Chiesi Italia, Eli Lilly, Genzyme, Janssen, Merck Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda and Teva; participation in advisory boards for Alexion, Biogen, Bristol Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme and Takeda; scientific direction of educational events for Biogen, Merck, Roche, Celgene, Bristol Myers Squibb, Lilly, Novartis and Sanofi-Genzyme; receives research support from Biogen Idec, Merck Serono, Novartis, Roche, the Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla and ARiSLA (Fondazione Italiana di Ricerca per la SLA). VF reports no disclosure relevant to the manuscript. NE has served as a member of advisory boards for Biogen, Merck, Novartis and Roche; has received grant income from the UK Multiple Sclerosis Society, MRC, PCORI and NIHR. CE has received funding for travelling and speaker honoraria from Biogen Idec and Bayer Schering. AGal has received honoraria from Biogen, Merck Serono, Mylan, Novartis, Roche, Sanofi-Genzyme and Teva for consulting services, speaking and/or travel support. AGar has received funding from the UK Multiple Sclerosis Society and has received speaker honoraria from the Multiple Sclerosis Academy. SG reports no disclosure relevant to the manuscript. SH has received travel funding and/or speaker honoraria from Biogen, Roche, Genzyme, Novartis, Bial, CSL Behring and Merck Serono. MK has received funding for travel and speaker honoraria from Bayer, Novartis, Merck, Biogen Idec and Teva Pharmaceutical Industries; and serves on scientific advisory boards for Biogen Idec, Merck Serono, Roche, Novartis and Gilead. ML has received honoraria from Biogen, Merck Serono, Novartis, Roche, Sanofi-Genzyme, Almirall and Bayer for consulting services, speaking and/or travel support. MM has served on scientific advisory boards for Bayer Schering, Biogen, Sanofi-Genzyme, Merck, Novartis, Teva, Mylan and Almirall; and has received consulting and/or speaker fees, research support or travel grants from Almirall, Bayer Schering, Biogen, CSL Behring, Sanofi-Genzyme, Merck, Novartis, Teva, Roche and Ultragenix. XM has received speaking honoraria and travel expenses for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Abbvie, Actelion, Alexion, Biogen, Bristol Myers Squibb/Celgene, EMD Serono, Genzyme, Hoffmann-La Roche, Immunic, Janssen Pharmaceuticals, Medday, Merck, Mylan, Nervgen, Novartis, Sandoz, Sanofi-Genzyme, Teva Pharmaceutical, TG Therapeutics, Excemed, MSIF and NMSS. CP has served on scientific advisory boards and received consulting and/or speaker fees from Almirall, Alexion, Biogen, Janssen, Roche, Merck and Novartis; and has received research support from Almirall, Biogen, Roche, Merck and Novartis. PP received speaker honoraria from Roche, Biogen, Novartis, Merck Serono, Bristol Myers Squibb and Genzyme; has received research support from the Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla. JR has received speaking honoraria and personal compensation for participating in advisory boards from Biogen-Idec, Genzyme, Merck Serono, Mylan, Novartis, Roche, Teva and Sanofi-Aventis. MAR received consulting fees from Biogen, Bristol Myers Squibb, Eli Lilly, Janssen and Roche; received speaker honoraria from AstraZeneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono, Novartis, Roche, Sanofi and Teva; and receives research support from the MS Society of Canada, the Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla. She is Associate Editor for Multiple Sclerosis and Related Disorders. AR serves on scientific advisory boards for Novartis, Sanofi-Genzyme, Synthetic MR, TensorMedical, Roche, Biogen and OLEA Medical; and has received speaker honoraria from Bayer, Sanofi-Genzyme, Merck Serono, Teva Pharmaceutical Industries, Novartis, Roche, Bristol Myers and Biogen. MLS reports no disclosure relevant to the manuscript. MZ has received honoraria for lecturing or participating in advisory boards, or financial support for attending scientific meetings from Alexion, Biogen, BMS-Celgene, Janssen, Genzyme, Merck, Novartis and Sanofi. CT received honoraria for speaking and travel grants from Biogen, Sanofi-Aventis, Merck Serono, Bayer-Schering, Teva, Genzyme, Almirall and Novartis. CG has received speaker honoraria and/or travel expenses for attending meetings from Bayer Schering Pharma, Sanofi-Aventis, Merck, Biogen, Novartis and Almirall.

      • Provenance and peer review Not commissioned; externally peer reviewed.

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