O Yildiz1, Z Mao2, A Adams3, N Dubuisson4, K Allen-Philbey5, G Giovannoni1, A Malaspina1, D Baker4, S Gnanapavan1, K Schmierer6. 1. The Blizard Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom; Clinical Board: Medicine (Neuroscience), The Royal London Hospital, Barts Health NHS Trust, London, United Kingdom. 2. The Blizard Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom; Department of Neurology, Shenzhen University General Hospital, Shenzhen University, Shenzhen, China; Shenzhen University Clinical Medical Academy, Shenzhen University, Shenzhen, China. 3. Department of Neuroradiology, The Royal London Hospital, Barts Health NHS Trust, London, United Kingdom. 4. The Blizard Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom. 5. Clinical Board: Medicine (Neuroscience), The Royal London Hospital, Barts Health NHS Trust, London, United Kingdom. 6. The Blizard Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, United Kingdom; Clinical Board: Medicine (Neuroscience), The Royal London Hospital, Barts Health NHS Trust, London, United Kingdom. Electronic address: k.schmierer@qmul.ac.uk.
Abstract
BACKGROUND: Evidence suggests people with non-relapsing deteriorating ("progressive") multiple sclerosis (pwPMS) may benefit from disease-modifying immune therapy (DMT). However, only one such treatment (ocrelizumab) has been licensed and is highly restricted to pwPMS suffering from the primary progressive phenotype. The difficulties assessing treatment outcome in pwPMS is one important reason for the lack of respective DMT. The concentration of neurofilaments in the cerebrospinal fluid (CSF) provides a biomarker of neuro-axonal damage, and both neurofilament light (NfL) and heavy chain (NfH) levels have been used as outcome indices and to guide treatment choices. METHODS: We report on two pwPMS, who were treated with subcutaneous cladribine undergoing CSF NfL testing, alongside MRI and clinical follow-up, before and after treatment. RESULTS: Cladribine treatment was well tolerated without any side effects. CSF NfL after treatment revealed significant reduction (by 73% and 80%, respectively) corroborating the MRI detectable drop in disease activity. Disability mildly progressed in one, and remained stable in the other pwPMS. CONCLUSIONS: pwPMS with detectable disease activity (MRI, elevated NfL) should be considered for DMT. NfL appears to be a sensitive index of treatment effect in pwPMS, and may be a useful outcome in clinical trials targeting this patient group. Over and above its licensed indication (relapsing MS), cladribine may be an effective treatment option for pwPMS.
BACKGROUND: Evidence suggests people with non-relapsing deteriorating ("progressive") multiple sclerosis (pwPMS) may benefit from disease-modifying immune therapy (DMT). However, only one such treatment (ocrelizumab) has been licensed and is highly restricted to pwPMS suffering from the primary progressive phenotype. The difficulties assessing treatment outcome in pwPMS is one important reason for the lack of respective DMT. The concentration of neurofilaments in the cerebrospinal fluid (CSF) provides a biomarker of neuro-axonal damage, and both neurofilament light (NfL) and heavy chain (NfH) levels have been used as outcome indices and to guide treatment choices. METHODS: We report on two pwPMS, who were treated with subcutaneous cladribine undergoing CSF NfL testing, alongside MRI and clinical follow-up, before and after treatment. RESULTS:Cladribine treatment was well tolerated without any side effects. CSF NfL after treatment revealed significant reduction (by 73% and 80%, respectively) corroborating the MRI detectable drop in disease activity. Disability mildly progressed in one, and remained stable in the other pwPMS. CONCLUSIONS: pwPMS with detectable disease activity (MRI, elevated NfL) should be considered for DMT. NfL appears to be a sensitive index of treatment effect in pwPMS, and may be a useful outcome in clinical trials targeting this patient group. Over and above its licensed indication (relapsing MS), cladribine may be an effective treatment option for pwPMS.
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