Medicine (RMH) - Research Publications

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    Effect of Disease-Modifying Therapy on Disability in Relapsing-Remitting Multiple Sclerosis Over 15 Years
    Kalincik, T ; Diouf, I ; Sharmin, S ; Malpas, C ; Spelman, T ; Horakova, D ; Havrdova, EK ; Trojano, M ; Izquierdo, G ; Lugaresi, A ; Prat, A ; Girard, M ; Duquette, P ; Grammond, P ; Jokubaitis, V ; Van der Walt, A ; Grand'Maison, F ; Sola, P ; Ferraro, D ; Shaygannejad, V ; Alroughani, R ; Hupperts, R ; Terzi, M ; Boz, C ; Lechner-Scott, J ; Pucci, E ; Van Pesch, V ; Granella, F ; Bergamaschi, R ; Spitaleri, D ; Slee, M ; Vucic, S ; Ampapa, R ; McCombe, P ; Ramo-Tello, C ; Prevost, J ; Olascoaga, J ; Cristiano, E ; Barnett, M ; Saladino, ML ; Sanchez-Menoyo, JL ; Hodgkinson, S ; Rozsa, C ; Hughes, S ; Moore, F ; Shaw, C ; Butler, E ; Skibina, O ; Gray, O ; Kermode, A ; Csepany, T ; Singhal, B ; Shuey, N ; Piroska, I ; Taylor, B ; Simo, M ; Sirbu, C-A ; Sas, A ; Butzkueven, H (LIPPINCOTT WILLIAMS & WILKINS, 2021-02-02)
    OBJECTIVE: To test the hypothesis that immunotherapy prevents long-term disability in relapsing-remitting multiple sclerosis (MS), we modeled disability outcomes in 14,717 patients. METHODS: We studied patients from MSBase followed for ≥1 year, with ≥3 visits, ≥1 visit per year, and exposed to MS therapy, and a subset of patients with ≥15-year follow-up. Marginal structural models were used to compare the cumulative hazards of 12-month confirmed increase and decrease in disability, Expanded Disability Status Scale (EDSS) step 6, and the incidence of relapses between treated and untreated periods. Marginal structural models were continuously readjusted for patient age, sex, pregnancy, date, disease course, time from first symptom, prior relapse history, disability, and MRI activity. RESULTS: A total of 14,717 patients were studied. During the treated periods, patients were less likely to experience relapses (hazard ratio 0.60, 95% confidence interval [CI] 0.43-0.82, p = 0.0016), worsening of disability (0.56, 0.38-0.82, p = 0.0026), and progress to EDSS step 6 (0.33, 0.19-0.59, p = 0.00019). Among 1,085 patients with ≥15-year follow-up, the treated patients were less likely to experience relapses (0.59, 0.50-0.70, p = 10-9) and worsening of disability (0.81, 0.67-0.99, p = 0.043). CONCLUSION: Continued treatment with MS immunotherapies reduces disability accrual by 19%-44% (95% CI 1%-62%), the risk of need of a walking aid by 67% (95% CI 41%-81%), and the frequency of relapses by 40-41% (95% CI 18%-57%) over 15 years. This study provides evidence that disease-modifying therapies are effective in improving disability outcomes in relapsing-remitting MS over the long term. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that, for patients with relapsing-remitting MS, long-term exposure to immunotherapy prevents neurologic disability.
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    Fast and safe: Optimising multiple sclerosis infusions during COVID-19 pandemic
    Rath, L ; Bui, MV ; Ellis, J ; Carey, J ; Baker, J ; Taylor, L ; Fernando, H ; Taylor, N ; Savage, P ; Richards, J ; Zhong, M ; Kalincik, T ; Skibina, O ; Wesselingh, R ; Nguyen, A-L ; Monif, M ; Butzkueven, H ; van der Walt, A (ELSEVIER SCI LTD, 2021-01)
    BACKGROUND: The COVID-19 pandemic challenges multiple sclerosis services to be innovative in delivering infusible therapies. To reduce time in clinical settings, and potential staff or space losses, we implemented rapid infusion protocols for selected patients. OBJECTIVE: To analyse the rate of infusion related reactions and patient experience of rapid infusions of natalizumab and ocrelizumab. To document time reduction patients spent in clinical settings during the COVID-19 pandemic. METHODS: Patients with prior exposure to at least three natalizumab or two 300mg ocrelizumab infusions were approved for rapid protocols. A retrospective audit and survey were completed. RESULTS: We analysed 269 rapid natalizumab infusions and 100 rapid ocrelizumab infusions. Infusion related reactions during the natalizumab or ocrelizumab infusions occurred in two patients (1.52%) and eight patients (8%), respectively. All infusion related reactions were mild to moderate and did not require infusion discontinuation. No infusion reactions occurred during the post-infusion observation. Patient experience was positive. CONCLUSION: Frequency or severity of infusion related reactions in rapid infusions were no different compared to published data. In the setting of COVID-19, pandemic rapid infusion protocols could potentially save hospital resources and limit patient exposure to a high-risk clinical setting while still maintaining ongoing treatment of multiple sclerosis.
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    COVID-19 in people with multiple sclerosis: A global data sharing initiative
    Peeters, LM ; Parciak, T ; Walton, C ; Geys, L ; Moreau, Y ; De Brouwer, E ; Raimondi, D ; Pirmani, A ; Kalincik, T ; Edan, G ; Simpson-Yap, S ; De Raedt, L ; Dauxais, Y ; Gautrais, C ; Rodrigues, PR ; McKenna, L ; Lazovski, N ; Hillert, J ; Forsberg, L ; Spelman, T ; McBurney, R ; Schmidt, H ; Bergmann, A ; Braune, S ; Stahmann, A ; Middleton, R ; Salter, A ; Bebo, BF ; Rojas, J ; van der Walt, A ; Butzkueven, H ; van der Mei, I ; Ivanov, R ; Hellwig, K ; do Olival, GS ; Cohen, JA ; Van Hecke, W ; Dobson, R ; Magyari, M ; Brum, DG ; Alonso, R ; Nicholas, R ; Bauer, J ; Chertcoff, A ; de Seze, J ; Louapre, C ; Comi, G ; Rijke, N (SAGE PUBLICATIONS LTD, 2020-09)
    BACKGROUND: We need high-quality data to assess the determinants for COVID-19 severity in people with MS (PwMS). Several studies have recently emerged but there is great benefit in aligning data collection efforts at a global scale. OBJECTIVES: Our mission is to scale-up COVID-19 data collection efforts and provide the MS community with data-driven insights as soon as possible. METHODS: Numerous stakeholders were brought together. Small dedicated interdisciplinary task forces were created to speed-up the formulation of the study design and work plan. First step was to agree upon a COVID-19 MS core data set. Second, we worked on providing a user-friendly and rapid pipeline to share COVID-19 data at a global scale. RESULTS: The COVID-19 MS core data set was agreed within 48 hours. To date, 23 data collection partners are involved and the first data imports have been performed successfully. Data processing and analysis is an on-going process. CONCLUSIONS: We reached a consensus on a core data set and established data sharing processes with multiple partners to address an urgent need for information to guide clinical practice. First results show that partners are motivated to share data to attain the ultimate joint goal: better understand the effect of COVID-19 in PwMS.