TY - JOUR T1 - Chronic lesion activity and disability progression in secondary progressive multiple sclerosis JF - BMJ Neurology Open JO - BMJ Neurol Open DO - 10.1136/bmjno-2021-000240 VL - 4 IS - 1 SP - e000240 AU - Vanessa Beynon AU - Ilena C George AU - Colm Elliott AU - Douglas L Arnold AU - Jun Ke AU - Huaihou Chen AU - Li Zhu AU - Chunlei Ke AU - Gavin Giovannoni AU - Matthew Scaramozza AU - Nolan Campbell AU - Daniel P Bradley AU - Nathalie Franchimont AU - Arie Gafson AU - Shibeshih Belachew Y1 - 2022/06/01 UR - http://neurologyopen.bmj.com/content/4/1/e000240.abstract N2 - Objective Slowly expanding lesions (SELs), a subgroup of chronic white matter lesions that gradually expand over time, have been shown to predict disability accumulation in primary progressive multiple sclerosis (MS) disease. However, the relationships between SELs, acute lesion activity (ALA), overall chronic lesion activity (CLA) and disability progression are not well understood. In this study, we examined the ASCEND phase III clinical trial, which compared natalizumab with placebo in secondary progressive MS (SPMS).Methods Patients with complete imaging datasets between baseline and week 108 (N=600) were analysed for SEL prevalence (the number and volume of SELs), disability progression, ALA (assessed by gadolinium-enhancing lesions and new T2-hyperintense lesions) and CLA (assessed by T1-hypointense lesion volume increase within baseline T2-non-enhancing lesions identified as SELs and non-SELs).Results CLA in both SELs and non-SELs was greater in patients with SPMS with confirmed disability progression than in those with no progression. In the complete absence of ALA at baseline and on study, SEL prevalence was significantly lower, while CLA within non-SELs remained associated with disability progression. Natalizumab decreased SEL prevalence and CLA in SELs and non-SELs compared with placebo.Conclusions This study shows that CLA in patients with SPMS is decreased but persists in the absence of ALA and is associated with disability progression, highlighting the need for therapeutics targeting all mechanisms of CLA, including smouldering inflammation and neurodegeneration.Trial registration number NCT01416181.Data may be obtained from a third party and are not publicly available. The datasets generated and analysed during the current study are not publicly available. The authors fully support sharing whenever possible. Requests for deidentified data should be made to Biogen via established company data-sharing policies and processes detailed on the website http://clinicalresearch.biogen.com/. ER -