Objective This study aimed to define the minimal evidence of disease activity (MEDA) during treatment that can be tolerated without exposing patients with relapsing-remitting multiple sclerosis at risk of long-term disability.
Methods We retrospectively collected data of patients followed up to 10 years after starting interferon beta or glatiramer acetate. Survival analyses explored the association between the long-term risk of reaching an Expanded Disability Status Scale≥6.0 and early clinical and MRI activity assessed after the first and second year of treatment. Early disease activity was classified by the so-called ‘MAGNIMS score’ (low: no relapses and <3 new T2 lesions; medium: no relapses and ≥3 new T2 lesions or 1 relapse and 0–2 new T2 lesions; high: 1 relapse and ≥3 new T2 lesions or ≥2 relapses) and the absence or presence of contrast-enhancing lesions (CELs).
Results At follow-up, 148/1036 (14.3%) patients reached the outcome: 61/685 (8.9%) with low score (reference category), 57/241 (23.7%) with medium score (HR=1.94, p=0.002) and 30/110 (27.3%) with high score (HR=2.47, p<0.001) after the first year of treatment. In the low score subgroup, the risk was further reduced in the absence (49/607, 8.1%) than in the presence of CELs (12/78, 15.4%; HR=2.11, p=0.01). No evident disease activity and low score in the absence of CELs shared the same risk (p=0.54). Similar findings were obtained even after the second year of treatment.
Conclusions Early marginal MRI activity of one to two new T2 lesions, in the absence of both relapses and CELs, is associated with a minor risk of future disability, thus representing a simple and valuable definition for MEDA.
- multiple sclerosis
- treatment response
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Contributors Conception and design of the study, drafting a significant portion of the manuscript/figures: LP, CG. Acquisition and analysis of data, revision of manuscript content: CM, SH, CC, LDG, NDR, S Rasia and S Ruggieri. Supervision and drafting the final version of the manuscript: SG, CT, CP.
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 LP: 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. CM: no disclosures. SH: travel funding and/or speaker honoraria from Biogen, Roche, Genzyme, Novartis and CSL Behring. CC: fees as invited speaker and travel grants for attending meeting from Serono, Biogen, Teva and Novartis. LDG: travel grants from Biogen, Novartis and Teva. NDR: speaker honoraria from Biogen Idec, Genzyme, Novartis, Sanofi-Aventis; funding for participation in advisory board to Novartis and Genzyme-Sanofi and for travel to scientific meetings from Biogen Idec, Teva, Sanofi-Genzyme, Roche, Almirall and Novartis. SG: fees as invited speaker or travel expenses for attending meeting from Biogen, Merck-Serono, Teva, Almirall, Sanofi-Aventis, Novartis and Genzyme. S Rasia: fees as invited speaker or travel expenses for attending meeting from Biogen, Merck-Serono, Teva, Sanofi, Novartis and Genzyme. S Ruggieri: speaking honoraria from Merck Serono and Teva. CT: honoraria for speaking and travel grants from Biogen, Sanofi-Aventis, Merck Serono, Bayer-Schering, Teva, Genzyme, Almirall and Novartis. CP: scientific advisory boards for Actelion, Biogen, Genzyme, Hoffmann-La Roche, Merck-Serono, Novartis, Sanofi and Teva; consulting and/or speaking fees, research support and travel grants from Allergan, Almirall, Biogen, Genzyme, Hoffmann-La Roche, Merck-Serono, Novartis, Sanofi and Teva. CG: fees as invited speaker or travel expenses for attending meeting from Biogen, Merck-Serono, Teva, Sanofi, Novartis and Genzyme.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on reasonable request.