A multi-centre longitudinal study analysing multiple sclerosis disease-modifying therapy prescribing patterns during the COVID-19 pandemic
Authors: Lal Anoushka P. , Foong Yi Chao , Sanfilippo Paul G. , Spelman Tim , Rath Louise , Levitz David , Fabis-Pedrini Marzena , Foschi Matteo , Habek Mario , Kalincik Tomas , Roos Izanne , Lechner-Scott Jeannette , John Nevin , Soysal Aysun , D’Amico Emanuele , Gouider Riadh , Mrabet Saloua , Gross-Paju Katrin , Cárdenas-Robledo Simón , Moghadasi Abdorreza Naser , Sa Maria Jose , Gray Orla , Oh Jiwon , Reddel Stephen , Ramanathan Sudarshini , Al-Harbi Talal , Altintas Ayse , Hardy Todd A. , Ozakbas Serkan , Alroughani Raed , Kermode Allan G. , Surcinelli Andrea , Laureys Guy , Eichau Sara , Prat Alexandre , Girard Marc , Duquette Pierre , Hodgkinson Suzanne , Ramo-Tello Cristina , Maimone Davide , McCombe Pamela , Spitaleri Daniele , Sanchez-Menoyo Jose Luis , Yetkin Mehmet Fatih , Baghbanian Seyed Mohammad , Karabudak Rana , Al-Asmi Abdullah , Jakob Gregor Brecl , Khoury Samia J. , Etemadifar Masoud , van Pesch Vincent , Buzzard Katherine , Taylor Bruce , Butzkueven Helmut , Van der Walt Anneke 
Published: June 2024

Abstract
Background
The COVID-19 pandemic raised concern amongst clinicians that disease-modifying therapies (DMT), particularly anti-CD20 monoclonal antibodies (mAb) and fingolimod, could worsen COVID-19 in people with multiple sclerosis (pwMS). This study aimed to examine DMT prescribing trends pre- and post-pandemic onset.

Methods
A multi-centre longitudinal study with 8,771 participants from MSBase was conducted. Two time periods were defined: pre-pandemic (March 11 2018–March 10 2020) and post-pandemic onset (March 11 2020–11 March 2022). The association between time and prescribing trends was analysed using multivariable mixed-effects logistic regression. DMT initiation refers to first initiation of any DMT, whilst DMT switches indicate changing regimen within 6 months of last use.

Results
Post-pandemic onset, there was a significant increase in DMT initiation/switching to natalizumab and cladribine [(Natalizumab-initiation: OR 1.72, 95% CI 1.39–2.13; switching: OR 1.66, 95% CI 1.40–1.98), (Cladribine-initiation: OR 1.43, 95% CI 1.09–1.87; switching: OR 1.67, 95% CI 1.41–1.98)]. Anti-CD20mAb initiation/switching decreased in the year of the pandemic, but recovered in the second year, such that overall odds increased slightly post-pandemic (initiation: OR 1.26, 95% CI 1.06–1.49; Switching: OR 1.15, 95% CI 1.02–1.29. Initiation/switching of fingolimod, interferon-beta, and alemtuzumab significantly decreased [(Fingolimod-initiation: OR 0.55, 95% CI 0.41–0.73; switching: OR 0.49, 95% CI 0.41–0.58), (Interferon-gamma-initiation: OR 0.48, 95% CI 0.41–0.57; switching: OR 0.78, 95% CI 0.62–0.99), (Alemtuzumab-initiation: OR 0.27, 95% CI 0.15–0.48; switching: OR 0.27, 95% CI 0.17–0.44)].

Conclusions
Post-pandemic onset, clinicians preferentially prescribed natalizumab and cladribine over anti-CD20 mAbs and fingolimod, likely to preserve efficacy but reduce perceived immunosuppressive risks. This could have implications for disease progression in pwMS. Our findings highlight the significance of equitable DMT access globally, and the importance of evidence-based decision-making in global health challenges.