Treatment reduces the incidence of newly appearing multiple sclerosis lesions evolving into chronic active, slowly expanding lesions: A retrospective analysis

Abstract

Chronic active lesions; Primary progressive multiple sclerosis; Volumetric MRI

Lesiones crónicas activas; Esclerosis múltiple primaria progresiva; Resonancia magnética volumétrica

Lesions actives cròniques; Esclerosi múltiple primària progressiva; Ressonància magnètica volumètrica

Background and purpose Newly appearing lesions in multiple sclerosis (MS) may evolve into chronically active, slowly expanding lesions (SELs), leading to sustained disability progression. The aim of this study was to evaluate the incidence of newly appearing lesions developing into SELs, and their correlation to clinical evolution and treatment. Methods A retrospective analysis of a fingolimod trial in primary progressive MS (PPMS; INFORMS, NCT 00731692) was undertaken. Data were available from 324 patients with magnetic resonance imaging scans up to 3 years after screening. New lesions at year 1 were identified with convolutional neural networks, and SELs obtained through a deformation-based method. Clinical disability was assessed annually by Expanded Disability Status Scale (EDSS), Nine-Hole Peg Test, Timed 25-Foot Walk, and Paced Auditory Serial Addition Test. Linear, logistic, and mixed-effect models were used to assess the relationship between the Jacobian expansion in new lesions and SELs, disability scores, and treatment status. Results One hundred seventy patients had ≥1 new lesions at year 1 and had a higher lesion count at screening compared to patients with no new lesions (median = 27 vs. 22, p = 0.007). Among the new lesions (median = 2 per patient), 37% evolved into definite or possible SELs. Higher SEL volume and count were associated with EDSS worsening and confirmed disability progression. Treated patients had lower volume and count of definite SELs (β = −0.04, 95% confidence interval [CI] = −0.07 to −0.01, p = 0.015; β = −0.36, 95% CI = −0.67 to −0.06, p = 0.019, respectively). Conclusions Incident chronic active lesions are common in PPMS, and fingolimod treatment can reduce their number.

A. Calvi is supported by the ECTRIMS post-doctoral training fellowship (2022), previously received a UK MS Society PhD studentship (2020), a Guarantors of Brain “Entry” clinical fellowship (2019), and an ECTRIMS-MAGNIMS fellowship (2018). He has received travel support from the UK MS society, ECTRIMS and NAIMS. Z. Mendelsohn and B. Kanber are supported by the National Institute for Health and Research (NIHR) Biomedical Research Centre (BRC) initiative at University College London Hospitals (UCLH). W. Hamed, J Stutters have nothing to disclose in relation to this study. D. Chard is a consultant for Hoffmann-La Roche. In the last three years he has been a consultant for Biogen, has received research funding from Hoffmann-La Roche, the International Progressive MS Alliance, the MS Society, the Medical Research Council, and the NIHR UCLH Biomedical Research Centre, and a speaker's honorarium from Novartis. He co-supervises a clinical fellowship at the National Hospital for Neurology and Neurosurgery, London, which is supported by Merck. C. Tur has received 2021 Merck's Award for the Investigation in Multiple Sclerosis, Junior Leader La Caixa Fellowship in 2020, ECTRIMS Post-doctoral Research Fellowship in 2015; honoraria and support for travelling from Merck Serono, Sanofi, Roche, TEVA Pharmaceuticals, Novartis, Biogen, Bayer, Ismar Healthcare. F. Barkhof is supported by the NIHR BRC initiative at UCLH, and he serves on the steering committee, or he is iDMC member for Biogen, Merck, Roche, EISAI and Prothena. Consultant for Roche, Biogen, Merck, IXICO, Jansen, Combinostics. Research agreements with Merck, Biogen, GE Healthcare, Roche. C. Gandini Wheeler-Kingshott has received funding from the MS Society (#77), Wings for Life (#169111), Horizon2020 (Human Brain Project SGA3, Specific Grant Agreement No. 945539), BRC (#BRC704/CAP/CGW), MRC (#MR/S026088/1), Ataxia UK. F. Prados received a Guarantors of Brain fellowship 2017-2020 and is supported by NIHR BRC initiative at UCLH. F. Barkhof, D. Mac Manus and C. Gandini Wheeler-Kingshott declare competing interests as share-holders in Queen Square Analytics LTD.