A multi-centre longitudinal study analysing multiple sclerosis disease-modifying therapy prescribing patterns during the COVID-19 pandemic.

Anti-CD20 monoclonal antibodies COVID-19 Cladribine Disease-modifying therapy Multiple sclerosis Natalizumab

Journal

Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161

Informations de publication

Date de publication:
27 Jun 2024
Historique:
received: 04 05 2024
accepted: 10 06 2024
revised: 09 06 2024
medline: 27 6 2024
pubmed: 27 6 2024
entrez: 27 6 2024
Statut: aheadofprint

Résumé

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. 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. 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)]. 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.

Sections du résumé

BACKGROUND 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 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 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 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.

Identifiants

pubmed: 38935148
doi: 10.1007/s00415-024-12518-7
pii: 10.1007/s00415-024-12518-7
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s).

Références

Barzegar M et al (2021) COVID-19 among patients with multiple sclerosis: a systematic review. Neurol Neuroimmunol Neuroinflamm 8:4
doi: 10.1212/NXI.0000000000001001
Leung MW et al (2022) Mapping the risk of infections in patients with multiple sclerosis: a multi-database study in the United Kingdom Clinical Practice Research Datalink GOLD and Aurum. Mult Scler 28(11):1808–1818
doi: 10.1177/13524585221094218 pubmed: 35575214 pmcid: 9442628
Chaudhry F et al (2020) COVID-19 in multiple sclerosis patients and risk factors for severe infection. J Neurol Sci 418:117147
doi: 10.1016/j.jns.2020.117147 pubmed: 32980780 pmcid: 7834402
Louapre C et al (2020) Clinical characteristics and outcomes in patients with coronavirus disease 2019 and multiple sclerosis. JAMA Neurol 77(9):1079–1088
doi: 10.1001/jamaneurol.2020.2581 pubmed: 32589189
Brownlee W et al (2020) Treating multiple sclerosis and neuromyelitis optica spectrum disorder during the COVID-19 pandemic. Neurology 94(22):949–952
doi: 10.1212/WNL.0000000000009507 pubmed: 32241953
Korsukewitz C, Reddel SW, Bar-Or A, Wiendl H (2020) Neurological immunotherapy in the era of COVID-19—looking for consensus in the literature. Nat Rev Neurol 16(9):493–505
doi: 10.1038/s41582-020-0385-8 pubmed: 32641860 pmcid: 7341707
Giovannoni G et al (2020) The COVID-19 pandemic and the use of MS disease-modifying therapies. Mult Scler Relat Disord 39:102073
doi: 10.1016/j.msard.2020.102073 pubmed: 32334820 pmcid: 7138156
Berger JR, Brandstadter R, Bar-Or A (2020) COVID-19 and MS disease-modifying therapies. Neurol Neuroimmunol Neuroinflamm 7:4
doi: 10.1212/NXI.0000000000000761
Safavi F, Nourbakhsh B, Azimi AR (2020) B-cell depleting therapies may affect susceptibility to acute respiratory illness among patients with multiple sclerosis during the early COVID-19 epidemic in Iran. Mult Scler Relat Disord 43:102195
doi: 10.1016/j.msard.2020.102195 pubmed: 32460086 pmcid: 7219389
Dalla Costa G et al (2020) Real-time assessment of COVID-19 prevalence among multiple sclerosis patients: a multicenter European study. Neurol Sci 41(7):1647–1650
doi: 10.1007/s10072-020-04519-x pubmed: 32617741 pmcid: 7331489
Januel E et al (2023) Association between anti-CD20 therapies and COVID-19 severity among patients with relapsing-remitting and progressive multiple sclerosis. JAMA Netw Open 6(6):e2319766–e2319766
doi: 10.1001/jamanetworkopen.2023.19766 pubmed: 37351881 pmcid: 10290250
Schiavetti I et al (2022) Severe outcomes of COVID-19 among patients with multiple sclerosis under anti-CD-20 therapies: a systematic review and meta-analysis. Multiple Scler Relat Disord 57:103358
doi: 10.1016/j.msard.2021.103358
Bsteh G et al (2022) Has the pandemic changed treatment strategy in multiple sclerosis? Mult Scler Relat Disord 63:103912
doi: 10.1016/j.msard.2022.103912 pubmed: 35636274 pmcid: 9125982
Zaheer R et al (2023) Impact of COVID-19 on prescribing patterns and treatment selection of disease modifying therapies in multiple sclerosis. Mult Scler Relat Disord 71:104575
doi: 10.1016/j.msard.2023.104575 pubmed: 36857853 pmcid: 9924032
Krett JD, Salter A, Newsome SD (2024) Era of COVID-19 in multiple sclerosis care. Neurol Clin 42(1):319–340
doi: 10.1016/j.ncl.2023.06.006 pubmed: 37980121
Thomas W et al (2022) Impact of the COVID-19 pandemic on the prescription of disease-modifying therapy for multiple sclerosis in England: a nationwide study. J Neurol Neurosurg Psychiatry 93(11):1229
doi: 10.1136/jnnp-2021-328340
Sormani MP et al (2021) DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France. Ann Clin Transl Neurol 8(8):1738–1744
doi: 10.1002/acn3.51408 pubmed: 34240579 pmcid: 8351392
Spelman T et al (2021) Increased rate of hospitalisation for COVID-19 among rituximab-treated multiple sclerosis patients: a study of the Swedish multiple sclerosis registry. Mult Scler J 28(7):1051–1059
doi: 10.1177/13524585211026272
Zanghì A et al (2022) Is it time for ocrelizumab extended interval dosing in relapsing remitting MS? Evidence from an Italian multicenter experience during the COVID-19 pandemic. Neurotherapeutics 19(5):1535–1545
doi: 10.1007/s13311-022-01289-6 pubmed: 36036858 pmcid: 9422942
Bisecco A et al (2024) Covid-19 outbreak in Italy: an opportunity to evaluate extended interval dosing of ocrelizumab in MS patients (P2–6010). Neurology 102(17):6251
doi: 10.1212/WNL.0000000000206347
Thompson AJ et al (2018) Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol 17(2):162–173
doi: 10.1016/S1474-4422(17)30470-2 pubmed: 29275977
Foong YC et al (2024) Comparing ocrelizumab to interferon/glatiramer acetate in people with multiple sclerosis over age 60. J Neurol Neurosurg Psychiatry 2:4
Carlini F et al (2023) Cladribine tablets mode of action, learning from the pandemic: a narrative review. Neurol Therapy 12(5):1477–1490
doi: 10.1007/s40120-023-00520-6
Preziosa P et al (2021) COVID-19 in cladribine-treated relapsing-remitting multiple sclerosis patients: a monocentric experience. J Neurol 268(8):2697–2699
doi: 10.1007/s00415-020-10309-4 pubmed: 33216223
De Angelis M et al (2020) Mild or no COVID-19 symptoms in cladribine-treated multiple sclerosis: two cases and implications for clinical practice. Mult Scler Relat Disord 45:102452
doi: 10.1016/j.msard.2020.102452 pubmed: 32823148 pmcid: 7428688
Comi G et al (2019) Effect of cladribine tablets on lymphocyte reduction and repopulation dynamics in patients with relapsing multiple sclerosis. Mult Scler Relat Disord 29:168–174
doi: 10.1016/j.msard.2019.01.038 pubmed: 30885375
Chisari CG et al (2021) Natalizumab administration in multiple sclerosis patients during active SARS-CoV-2 infection: a case series. BMC Neurol 21(1):462
doi: 10.1186/s12883-021-02421-3 pubmed: 34839814 pmcid: 8627841
Landi D et al (2022) Safety of Natalizumab infusion in multiple sclerosis patients during active SARS-CoV-2 infection. Mult Scler Relat Disord 57:103345
doi: 10.1016/j.msard.2021.103345 pubmed: 35158454
Aguirre C et al (2020) Covid-19 in a patient with multiple sclerosis treated with natalizumab: May the blockade of integrins have a protective role? Mult Scler Relat Disord 44:102250
doi: 10.1016/j.msard.2020.102250 pubmed: 32531754 pmcid: 7831671
Sigrist CJ, Bridge A, Le Mercier P (2020) A potential role for integrins in host cell entry by SARS-CoV-2. Antiviral Res 177:104759
doi: 10.1016/j.antiviral.2020.104759 pubmed: 32130973 pmcid: 7114098
Hada M, Mosholder AD, Leishear K, Perez-Vilar S (2022) Systematic review of risk of SARS-CoV-2 infection and severity of COVID-19 with therapies approved to treat multiple sclerosis. Neurol Sci 43(3):1557–1567
doi: 10.1007/s10072-021-05846-3 pubmed: 35006442 pmcid: 8743352
Simpson-Yap S et al (2021) Associations of disease-modifying therapies with COVID-19 severity in multiple sclerosis. Neurology 97(19):e1870–e1885
doi: 10.1212/WNL.0000000000012753 pubmed: 34610987 pmcid: 8601210
Arvin AM et al (2015) Varicella-zoster virus infections in patients treated with fingolimod: risk assessment and consensus recommendations for management. JAMA Neurol 72(1):31–39
doi: 10.1001/jamaneurol.2014.3065 pubmed: 25419615 pmcid: 5391035
Luna G et al (2020) Infection risks among patients with multiple sclerosis treated with fingolimod, natalizumab, rituximab, and injectable therapies. JAMA Neurol 77(2):184–191
doi: 10.1001/jamaneurol.2019.3365 pubmed: 31589278
Barzegar M et al (2020) COVID-19 infection in a patient with multiple sclerosis treated with fingolimod. Neurol Neuroimmunol Neuroinflamm 7:4
doi: 10.1212/NXI.0000000000000753
Sullivan R et al (2021) COVID-19 infection in fingolimod- or siponimod-treated patients: case series. Neurol Neuroimmunol Neuroinflamm 9:1
Teymouri S et al (2023) The effect of Fingolimod on patients with moderate to severe COVID-19. Pharmacol Res Perspect 11(1):e01039
doi: 10.1002/prp2.1039 pubmed: 36567519
Baker D et al (2020) COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases. Clin Exp Immunol 202(2):149–161
doi: 10.1111/cei.13495 pubmed: 32671831 pmcid: 7405500
Ciotti JR, Valtcheva MV, Cross AH (2020) Effects of MS disease-modifying therapies on responses to vaccinations: a review. Mult Scler Relat Disord 45:102439
doi: 10.1016/j.msard.2020.102439 pubmed: 32769063 pmcid: 7395588

Auteurs

Anoushka P Lal (AP)

Department of Neuroscience, Central Clinical School, The Alfred, Melbourne, VIC, Australia.
Department of Neurology, The Alfred Hospital, 55 Commercial Road, Melbourne, 3004, Australia.

Yi Chao Foong (YC)

Department of Neuroscience, Central Clinical School, The Alfred, Melbourne, VIC, Australia.
Department of Neurology, The Alfred Hospital, 55 Commercial Road, Melbourne, 3004, Australia.
Royal Hobart Hospital, Hobart, Australia.

Paul G Sanfilippo (PG)

Department of Neuroscience, Central Clinical School, The Alfred, Melbourne, VIC, Australia.

Tim Spelman (T)

Department of Neuroscience, Central Clinical School, The Alfred, Melbourne, VIC, Australia.

Louise Rath (L)

Department of Neuroscience, Central Clinical School, The Alfred, Melbourne, VIC, Australia.

David Levitz (D)

Department of Neuroscience, Central Clinical School, The Alfred, Melbourne, VIC, Australia.

Marzena Fabis-Pedrini (M)

Perron Institute for Neurological and Translational Science, The University of Western Australia, Perth, Australia.
Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, Australia.

Matteo Foschi (M)

Department of Neuroscience, MS Center, Neurology Unit, S. Maria Delle Croci Hospital, AUSL Romagna, Ravenna, Italy.
Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L'Aquila, L'Aquila, Italy.

Mario Habek (M)

Department of Neurology, University Hospital Center Zagreb, Zagreb, Croatia.
School of Medicine, University of Zagreb, Zagreb, Croatia.

Tomas Kalincik (T)

Department of Neurology, Neuroimmunology Centre, Royal Melbourne Hospital, Melbourne, Australia.
CORe, Department of Medicine, University of Melbourne, Melbourne, Australia.

Izanne Roos (I)

Department of Neurology, Neuroimmunology Centre, Royal Melbourne Hospital, Melbourne, Australia.

Jeannette Lechner-Scott (J)

Hunter Medical Research Institute, University Newcastle, Newcastle, Australia.

Nevin John (N)

Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Australia.
Department of Neurology, Monash Health, Clayton, Australia.

Aysun Soysal (A)

Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases, Istanbul, Turkey.

Emanuele D'Amico (E)

Medical and Surgical Sciences, Universita Di Foggia, Foggia, Italy.

Riadh Gouider (R)

Department of Neurology, LR 18SP03, Clinical Investigation Centre Neurosciences and Mental Health, Razi University Hospital, Tunis, Tunisia.
Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.

Saloua Mrabet (S)

Department of Neurology, LR 18SP03, Clinical Investigation Centre Neurosciences and Mental Health, Razi University Hospital, Tunis, Tunisia.
Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.

Katrin Gross-Paju (K)

Multiple Sclerosis Centre, West-Tallinn Central Hospital, Tallinn, Estonia.

Simón Cárdenas-Robledo (S)

Department of Neurology, Centro de Esclerosis Múltiple (CEMHUN), Hospital Universitario Nacional de Colombia Bogota, Bogota, Colombia.
Departamento de Medicina InternaFacultad de Medicina, Universidad Nacional de Colombia, Bogota, Colombia.

Abdorreza Naser Moghadasi (AN)

Multiple Research Centre, Neuroscience Institute, Tehran University of Medical Science, Tehran, Iran.

Maria Jose Sa (MJ)

Department of Neurology, Centro Hospitalar Universitario de Sao Joao, Porto, Portugal.

Orla Gray (O)

South Eastern HSC Trust, Belfast, UK.

Jiwon Oh (J)

St. Michael's Hospital, Toronto, Canada.

Stephen Reddel (S)

Department of Neurology, Concord Repatriation General Hospital, Sydney, Australia.

Sudarshini Ramanathan (S)

Translational Neuroimmunology Group, Kids Neuroscience Centre and Brain and Mind Centre, Concord Hospital, Sydney, Australia.

Talal Al-Harbi (T)

Neurology Department, King Fahad Specialist Hospital-Dammam, Dammam, Saudi Arabia.

Ayse Altintas (A)

Department of Neurology, School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), İstanbul, Turkey.

Todd A Hardy (TA)

Department of Neurology, Concord Repatriation General Hospital, Sydney, Australia.

Serkan Ozakbas (S)

Izmir University of Economics, Medical Point Hospital, Izmir, Turkey.
Multiple Sclerosis Research Association, Izmir, Turkey.

Raed Alroughani (R)

Division of Neurology, Department of Medicine, Amiri Hospital, Sharq, Kuwait.

Allan G Kermode (AG)

Perron Institute for Neurological and Translational Science, The University of Western Australia, Perth, Australia.
Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, Australia.

Andrea Surcinelli (A)

Department of Neuroscience, MS Center, Neurology Unit, S. Maria Delle Croci Hospital, AUSL Romagna, Ravenna, Italy.

Guy Laureys (G)

Department of Neurology, University Hospital Ghent, Ghent, Belgium.

Sara Eichau (S)

Department of Neurology, Hospital Universitario Virgen Macarena, Seville, Spain.

Alexandre Prat (A)

CHUM and Universite de Montreal, Montreal, Canada.

Marc Girard (M)

CHUM and Universite de Montreal, Montreal, Canada.

Pierre Duquette (P)

CHUM and Universite de Montreal, Montreal, Canada.

Suzanne Hodgkinson (S)

Immune Tolerance Laboratory Ingham Institute and Department of Medicine, UNSW, Sydney, Australia.

Cristina Ramo-Tello (C)

Department of Neuroscience, Hospital Germans Trias I Pujol, Badalona, Spain.

Davide Maimone (D)

Centro Sclerosi Multipla, UOC Neurologia, Azienda Ospedaliera Per L'Emergenza Cannizzaro, Catania, Italy.

Pamela McCombe (P)

University of Queensland, Brisbane, Australia.
Royal Brisbane and Women's Hospital, Brisbane, Australia.

Daniele Spitaleri (D)

Azienda Ospedaliera Di Rilievo Nazionale San Giuseppe Moscati Avellino, Avellino, Italy.

Jose Luis Sanchez-Menoyo (JL)

Department of Neurology, Galdakao-Usansolo University Hospital, Osakidetza-Basque Health Service, Galdakao, Spain.

Mehmet Fatih Yetkin (MF)

Department of Neurology, Erciyes University, Kayseri, Turkey.

Seyed Mohammad Baghbanian (SM)

Neurology Department, Booalisina Hospital, Mazandaran University of Medical Sciences, Sari, Iran.
Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Rana Karabudak (R)

Department of Neurological Sciences, Faculty of Medicine, Yeditepe University, Istanbul, Turkey.
Neuroimmunology Unit, Koşuyolu Hospitals, Istanbul, Turkey.

Abdullah Al-Asmi (A)

College of Medicine & Health Sciences and Sultan Qaboos University Hospital, Sultan Qaboos University, Al-Khodh, Oman.

Gregor Brecl Jakob (GB)

Department of Neurology, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.

Samia J Khoury (SJ)

Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut, Lebanon.

Masoud Etemadifar (M)

Neurology, Dr. Etemadifar MS Institute, Isfahan University of Medical Sciences, Isfahan, Iran.

Vincent van Pesch (V)

Department of Neurology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.

Katherine Buzzard (K)

Department of Neurosciences, Box Hill Hospital, Box Hill, Australia.

Bruce Taylor (B)

Royal Hobart Hospital, Hobart, Australia.

Helmut Butzkueven (H)

Department of Neuroscience, Central Clinical School, The Alfred, Melbourne, VIC, Australia.
Department of Neurology, The Alfred Hospital, 55 Commercial Road, Melbourne, 3004, Australia.

Anneke Van der Walt (A)

Department of Neuroscience, Central Clinical School, The Alfred, Melbourne, VIC, Australia. anneke.vanderwalt@monash.edu.
Department of Neurology, The Alfred Hospital, 55 Commercial Road, Melbourne, 3004, Australia. anneke.vanderwalt@monash.edu.

Classifications MeSH