I Dekker1, C E Leurs2, M H J Hagens2, Z L E van Kempen2, I Kleerekooper2, B I Lissenberg-Witte3, F Barkhof4, B M J Uitdehaag2, L J Balk2, M P Wattjes5, J Killestein2. 1. Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Radiology & Nuclear Medicine, MS Center Amsterdam, Amsterdam Neuroscience, De Boelelaan 1117 Amsterdam, the Netherlands; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Neurology, MS Center Amsterdam, Amsterdam Neuroscience, De Boelelaan 1117 Amsterdam, the Netherlands. Electronic address: i.dekker1@amsterdamumc.nl. 2. Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Neurology, MS Center Amsterdam, Amsterdam Neuroscience, De Boelelaan 1117 Amsterdam, the Netherlands. 3. Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Epidemiology and Biostatistics, Amsterdam Neuroscience, De Boelelaan 1117 Amsterdam, the Netherlands. 4. Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Radiology & Nuclear Medicine, MS Center Amsterdam, Amsterdam Neuroscience, De Boelelaan 1117 Amsterdam, the Netherlands; Institutes of Neurology and Healthcare Engineering, UCL, London, United Kingdom. 5. Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Radiology & Nuclear Medicine, MS Center Amsterdam, Amsterdam Neuroscience, De Boelelaan 1117 Amsterdam, the Netherlands; Department of Diagnostic and Interventional Neuroradiology, Hannover Medical School, Hannover, Germany.
Abstract
BACKGROUND: Natalizumab is an effective treatment for relapsing-remitting multiple sclerosis (RRMS). Data on clinical and imaging measures predictive of disease activity and progression during treatment is limited. OBJECTIVE: To determine clinical and imaging predictors of long-term inflammatory disease activity and disability progression in RRMS patients on natalizumab. METHODS: Patients (n = 135) were selected from our prospective observational natalizumab cohort and monitored using brain MRI and extensive clinical testing. Progression and improvement on the Expanded Disability Status Scale (EDSS), no evidence of disease activity (NEDA) and no evidence of progression or active disease (NEPAD) status were determined using measurements after the initial phase of inflammation and the early anti-inflammatory impact of natalizumab. RESULTS: EDSS progression was seen in 43.7% of patients and EDSS improvement in 17.8%. Median follow-up was 4.9 years (IQR 3.6-6.0). Patients with a longer disease duration at natalizumab initiation have a higher hazard for earlier EDSS progression (HR 1.05, CI 1.00-1.09, p = 0.037) and a higher pre-baseline relapse rate predicted a longer NEPAD status (HR 1.70, CI 1.06-2.72, p = 0.028). CONCLUSION: The results suggest that starting natalizumab early, during active inflammatory disease results in a more favourable outcome. When taking into account early inflammation and the impact of natalizumab on disease activity during the initial treatment phase, a higher than expected proportion of patients showed disability progression.
BACKGROUND:Natalizumab is an effective treatment for relapsing-remitting multiple sclerosis (RRMS). Data on clinical and imaging measures predictive of disease activity and progression during treatment is limited. OBJECTIVE: To determine clinical and imaging predictors of long-term inflammatory disease activity and disability progression in RRMS patients on natalizumab. METHODS:Patients (n = 135) were selected from our prospective observational natalizumab cohort and monitored using brain MRI and extensive clinical testing. Progression and improvement on the Expanded Disability Status Scale (EDSS), no evidence of disease activity (NEDA) and no evidence of progression or active disease (NEPAD) status were determined using measurements after the initial phase of inflammation and the early anti-inflammatory impact of natalizumab. RESULTS: EDSS progression was seen in 43.7% of patients and EDSS improvement in 17.8%. Median follow-up was 4.9 years (IQR 3.6-6.0). Patients with a longer disease duration at natalizumab initiation have a higher hazard for earlier EDSS progression (HR 1.05, CI 1.00-1.09, p = 0.037) and a higher pre-baseline relapse rate predicted a longer NEPAD status (HR 1.70, CI 1.06-2.72, p = 0.028). CONCLUSION: The results suggest that starting natalizumab early, during active inflammatory disease results in a more favourable outcome. When taking into account early inflammation and the impact of natalizumab on disease activity during the initial treatment phase, a higher than expected proportion of patients showed disability progression.
Authors: Zoë Ygj van Lierop; Luuk Wieske; Marleen Ja Koel-Simmelink; Madhurima Chatterjee; Iris Dekker; Cyra E Leurs; Eline Aj Willemse; Bastiaan Moraal; Frederik Barkhof; Filip Eftimov; Bernhard Mj Uitdehaag; Joep Killestein; Charlotte E Teunissen Journal: Mult Scler Date: 2021-04-23 Impact factor: 6.312
Authors: Michael Guger; Christian Enzinger; Fritz Leutmezer; Franziska Di Pauli; Jörg Kraus; Stefan Kalcher; Erich Kvas; Thomas Berger Journal: J Neurol Date: 2021-04-22 Impact factor: 4.849