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., Competing Interests: 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., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)