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Potential beneficial effect of IFN-β1a and ocrelizumab in people with MS during the COVID-19 pandemic

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Abstract

Background/Aim

Disease-modifying therapy (DMT) has led to added challenges in the management of people with multiple sclerosis (pwMS) during the COVID-19 era. It can reduce relapse in MS or slow down disease progression, but some DMTs can increased risk of infection. The aim of study was to evaluate risk and severity of COVID-19 in pwMS.

Methods

The examined group of pwMS were divided in group treated with IFN-β1a, group treated with ocrelizumab and untreated group. The examination included impact of age, gender, duration of MS, type of MS, vaccination status and Expanded Disability Status Scale (EDSS) on the risk and severity of COVID-19 infection. A diagnosis of COVID-19 in pwMS was confirmed by positive polymerase-chain-reaction (PCR) or antigen test.

Results

Out of 207 pwMS, 82 patients were treated with ocrelizumab, 63 with IFN-β1a, while 62 patients were untreated pwMS. The average duration of the MS was longer in the group of patients treated with ocrelizumab than in the group treated with IFN-β1a (p < 0.05). EDSS was higher in the ocrelizumab group compared to the other two groups (p < 0.001). Untreated (more often unvaccinated) had the same COVID frequency as ocrelizumab-treated (more vaccinated, but higher EDSS). The multivariate logistic regression model indicated that administration of IFN-β1a reduces the risk of COVID-19 infection (p = 0.001, OR = 0.381, 95% CI 0.602–0.160). The use of both DMTs, driven mainly by the IFN-β1a effect, reduces the risk of moderate and severe COVID-19 (p < 0.05, OR = 0.105, 95% CI 0.011–0.968).

Conclusion

This study provides evidence that IFN-β1a can reduce the frequency of COVID-19 infection and that two DMTs, driven mainly by the IFN-β1a effect, do not increase the risk of moderate/severe COVID-19.

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References

  1. Howard J, Trevick S, Younger DS (2016) Epidemiology of multiple sclerosis. NeurolClin 34(4):919–939. https://doi.org/10.1016/j.ncl.2016.06.016

    Article  Google Scholar 

  2. MSIF (2020) Atlas of MS 2020: Mapping multiple sclerosis around the world. Key Epidemiology Findings. Multiple Sclerosis International Federation

  3. Tafti D, Ehsan M, Xixis KL (2022) Multiple sclerosis. In: StatPearls [Internet]. Treasure Island (FL). Available from: https://www.ncbi.nlm.nih.gov/books/NBK499849/

  4. Rotstein DL, Healy BC, Malik MT et al (2015) Evaluation of no evidence of disease activity in a 7-year longitudinal multiple sclerosis cohort. JAMA Neurol 72:152–158

    Article  PubMed  Google Scholar 

  5. Jacobs JJL (2020) Neutralizing antibodies mediate virus-immune pathology of COVID-19. Med Hypotheses 143:109884

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Filipi M, Jack S (2019) Interferons in the treatment of multiple sclerosis: a clinical efficacy, safety, and tolerability update. Int J MS Care 22(4):165–172. https://doi.org/10.7224/1537-2073.2018-063

  7. Frieman M, Yount B, Heise M, Kopecky-Bromberg SA, Palese P, Baric RS (2017) Severe acute respiratory syndrome coronavirus ORF6 antagonizes STAT1 function by sequestering nuclear import factors on the rough endoplasmic reticulum/Golgi membrane. J Virol 81(18):9812–9824. https://doi.org/10.1128/JVI.01012-07

  8. Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Montalban X, Rammohan KW, Selmaj K, Traboulsee A, Wolinsky JS, Arnold DL, Klingelschmitt G, Masterman D, Fontoura P, Belachew S, Chin P, Mairon N, Garren H, Kappos L (2017) OPERA I and OPERA II clinical investigators. ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med 376(3):221–234. https://doi.org/10.1056/NEJMoa1601277

  9. Hughes R, Whitley L, Fitovski K, Schneble HM, Muros E, Sauter A, Craveiro L, Dillon P, Bonati U, Jessop N, Pedotti R, Koendgen H (2021) COVID-19 in ocrelizumab-treated people with multiple sclerosis. Mult Scler Relat Disord 49:102725. https://doi.org/10.1016/j.msard.2020.102725

  10. Simpson-Yap S, De Brouwer E, Kalincik T et al (2021) Associations of disease-modifying therapies with COVID-19 severity in multiple sclerosis. Neurology 97(19):e1870–e1885. https://doi.org/10.1212/WNL.0000000000012753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Cucinotta D, Vanelli M (2020) WHO declares COVID-19 a pandemic. Acta Biomed 91(1):157–160. https://doi.org/10.23750/abm.v91i1.9397.PMID:32191675;PMCID:PMC7569573

    Article  PubMed  PubMed Central  Google Scholar 

  12. Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J, Xing F, Liu J, Yip CC, Poon RW, Tsoi HW, Lo SK, Chan KH, Poon VK, Chan WM, Ip JD, Cai JP, Cheng VC, Chen H, Hui CK, Yuen KY (2020) A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet 395(10223):514–523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Weiss P, Murdoch DR (2020) Clinical course and mortality risk of severe COVID-19. Lancet 395(10229):1014–1015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Xu PP, Tian RH, Luo S et al (2020) Risk factors for adverse clinical outcomes with COVID-19 in China: a multicenter, retrospective, observational study. Theranostics 10:6372–6383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Lupu D, Tiganasu R (2022) COVID-19 and the efficiency of health systems in Europe. Health Econ Rev 12:14. https://doi.org/10.1186/s13561-022-00358-y

    Article  PubMed  PubMed Central  Google Scholar 

  16. Wijnands JM, Kingwell E, Zhu F, Zhao Y, Fisk JD, Evans C, Marrie RA (2017) Infection-related health care utilization among people with and without multiple sclerosis. Mult Scler 23(11):1506–1516. https://doi.org/10.1177/1352458516681198

    Article  PubMed  Google Scholar 

  17. Steelman AJ (2015) Infection as an environmental trigger of multiple sclerosis disease exacerbation. Front Immunol 6:520. https://doi.org/10.3389/fimmu.2015.00520

    Article  PubMed  PubMed Central  Google Scholar 

  18. Iaffaldano P, Lucisano G, Manni A, Paolicelli D, Patti F, Capobianco M, Brescia Morra V, Sola P, Pesci I, Lus G, De Luca G, Lugaresi A, Cavalla P, Montepietra S, Maniscalco GT, Granella F, Ragonese P, Vianello M, Brambilla L, Totaro R, Toscano S, Malucchi S, Petracca M, Moiola L, Ferraro D, Lepore V, Mosconi P, Ponzio M, Tedeschi G, Comi G, Battaglia MA, Filippi M, Amato MP, Trojano M (2022) Italian MS Register. Risk of getting COVID-19 in people with multiple sclerosis: a case–control study. Neurol Neuroimmunol Neuroinflamm 9(2):e1141. https://doi.org/10.1212/NXI.0000000000001141

  19. Mallucci G, Zito A, Baldanti F et al (2021) Safety of disease-modifying treatments in SARS-CoV-2 antibody-positive multiple sclerosis patients. MultSclerRelatDisord 49:102754

    CAS  Google Scholar 

  20. Fernandes PM, O’Neill M, Kearns PKA et al (2020) Impact of the first COVID-19 pandemic wave on the Scottish Multiple Sclerosis Register population. Wellcome Open Res 5:276

    Article  PubMed  PubMed Central  Google Scholar 

  21. Costabile T, Carotenuto A, Lavorgna L, Borriello G, Moiola L, Inglese M, Petruzzo M, Trojsi F, Ianniello A, Nozzolillo A, Cellerino M, Boffa G, Rosa L, Servillo G, Moccia M, Bonavita S, Filippi M, Lanzillo R, Brescia Morra V, Petracca M (2020) COVID-19 pandemic and mental distress in multiple sclerosis: Implications for clinical management. Eur J Neurol. 28(10):3375–3383. https://doi.org/10.1111/ene.14580

  22. Australian National COVID-19 Clinical Evidence Taskforce. Australian guidelines for the clinical care of people with COVID-19, Version 16. Australian National COVID-19 Clinical Evidence Taskforce; 2020 [cited 2020 August 2]. Available from https://covid19evidence.net.au/

  23. Federation MSI (2022) MS, the coronavirus and vaccines—updated global advice. 2021 [cited 2022 Feb 8 2022]. Available from https://www.msif.org/news/2020/02/10/the-coronavirus-and-ms-what-you-nee

  24. Moss BP, Mahajan KR, Bermel RA, Hellisz K, Hua LH, Hudec T, Husak S, McGinley MP, Ontaneda D, Wang Z, Weber M, Tagliani P, Cárdenas-Robledo S, Zabalza A, Arrambide G, Carbonell-Mirabent P, Rodríguez-Barranco M, Sastre-Garriga J, Tintore M, Montalban X, Douglas M, Ogbuokiri E, Aravidis B, Cohen JA, Mowry EM, Fitzgerald KC. (2020) Multiple sclerosis management during the COVID-19 pandemic. Mult Scler. 26(10):1163–1171. https://doi.org/10.1177/1352458520948231

  25. Berger JR, Brandstadter R, Bar-Or A (2020) (2020) COVID-19 and MS disease-modifying therapies. Neurol Neuroimmunol Neuroinflamm 7(4):e761. https://doi.org/10.1212/NXI.0000000000000761

    Article  PubMed  PubMed Central  Google Scholar 

  26. Monk PD, Marsden RJ, Tear VJ, Brookes J, Batten TN, Mankowski M, Gabbay FJ, Davies DE, Holgate ST, Ho LP, Clark T, Djukanovic R, Wilkinson TMA (2021) Inhaled Interferon Beta COVID-19 Study Group. Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Respir Med 9(2):196–206. https://doi.org/10.1016/S2213-2600(20)30511-7

  27. Freedman MS, Jack D, Murgasova Z, Todorovic M, Seitzinger A (2021) Outcomes of COVID-19 among patients treated with subcutaneous interferon beta-1a for multiple sclerosis. MultSclerRelatDisord 56:103283. https://doi.org/10.1016/j.msard.2021.103283

  28. Salter A, Fox RJ, Newsome SD, Halper J, Li DKB, Kanellis P, Costello K, Bebo B, Rammohan K, Cutter GR, Cross AH (2021) Outcomes and risk factors associated with SARS-CoV-2 infection in a North American registry of patients with multiple sclerosis. JAMA Neurol 78(6):699–708. https://doi.org/10.1001/jamaneurol.2021.0688

    Article  PubMed  Google Scholar 

  29. Sosa JP, Ferreira Caceres MM, Ross Comptis J, Quiros J, Príncipe-Meneses FS, Riva-Moscoso A, Belizaire MP, Malanyaon FQ, Agadi K, Jaffery SS, Sahajwani J, Arshia A, Senatus A, Verdecia G, Akano L, Razzack AA, Salam S, Gadamidi VK, Marian S (2021) Effects of interferon beta in COVID-19 adult patients: systematic review. Infect Chemother 53(2):247–260. https://doi.org/10.3947/ic.2021.0028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Maniscalco GT, Manzo V, Ferrara AL, Perrella A, Di Battista M, Salvatore S, Graziano D, Viola A, Amato G, Moreggia O, Di Giulio Cesare D, Barbato S, Servillo G, Longo K, Di Giovanni M, Scarpati B, Muggianu SM, Longo G, Russo G, Andreone V, De Rosa V (2022) Interferon Beta-1a treatment promotes SARS-CoV-2 mRNA vaccine response in multiple sclerosis subjects. MultSclerRelatDisord 58:103455. https://doi.org/10.1016/j.msard.2021.103455

  31. Golshani M, Hrdy J (2022) Multiple sclerosis patients and disease modifying therapies: impact on immune responses against COVID-19 and SARS-CoV-2 vaccination. Vaccines 10(2):279. https://doi.org/10.3390/vaccines10020279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Meltzer DO, Best TJ, Zhang H, Vokes T, Arora VM (2021) Association of vitamin D levels, race/ethnicity, and clinical characteristics with COVID-19 test results. JAMA Netw Open 4(3):e214117. https://doi.org/10.1001/jamanetworkopen.2021.4117

    Article  PubMed  PubMed Central  Google Scholar 

  33. Feng X, Wang Z, Howlett-Prieto Q, Einhorn N, Causevic S (2019) Vitamin D enhances responses to interferon-β in MS. Neurol Neuroimmunol Neuroinflamm 6(6):e622. https://doi.org/10.1212/NXI.0000000000000622

    Article  PubMed  PubMed Central  Google Scholar 

  34. Wu X, Wang L, Shen L, Tang K (2022) Response of COVID-19 vaccination in multiple sclerosis patients following disease-modifying therapies: a meta-analysis. EBioMedicine 81:104102. https://doi.org/10.1016/j.ebiom.2022.104102

  35. Alroughani R, Inshasi JS, Al-Hashel J, Alkhaboury J, Alsalti A, Suwaidi RA, Hassino LH, Ahmed SF (2022) Incidence, severity, outcomes, and risk factors of COVID-19 in multiple sclerosis: an observational study in the Middle East. Mult Scler Relat Disord 59:103579. https://doi.org/10.1016/j.msard.2022.103579

  36. Sormani MP, De Rossi N, Schiavetti I, Carmisciano L, Cordioli C, Moiola L, Radaelli M, Immovilli P, Capobianco M, Trojano M, Zaratin P, Tedeschi G, Comi G, Battaglia MA, Patti F, Salvetti M; Musc-19 Study Group (2021) Disease-modifying therapies and coronavirus disease 2019 severity in multiple sclerosis. Ann Neurol 89(4):780–789. https://doi.org/10.1002/ana.26028

  37. Möhn N, Konen FF, Pul R, Kleinschnitz C, Prüss H, Witte T, Stangel M (2020) Experience in multiple sclerosis patients with COVID-19 and disease-modifying therapies: a review of 873 published cases. J Clin Med 9(12):4067. https://doi.org/10.3390/jcm9124067

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Schiavetti I, Ponzano M, Signori A, Bovis F, Carmisciano L, Sormani MP (2022) Severe outcomes of COVID-19 among patients with multiple sclerosis under anti-CD-20 therapies: a systematic review and meta-analysis. MultSclerRelatDisord 57:103358. https://doi.org/10.1016/j.msard.2021.103358

  39. Hughes R, Whitley L, Fitovski K, Schneble HM, Muros E, Sauter A, Craveiro L, Dillon P, Bonati U, Jessop N, Pedotti R, Koendgen H (2020) COVID-19 in ocrelizumab-treated people with multiple sclerosis. Mult Scler Relat Disord 49:102725. https://doi.org/10.1016/j.msard.2020.102725

  40. Inshasi J, Alroughani R, Al-Asmi A, Alkhaboury J, Alsalti A, Boshra A, Canibano B, Deleu D, Ahmed SF, Shatila A, Thakre M (2021) Expert consensus and narrative review on the management of multiple sclerosis in the Arabian Gulf in the COVID-19 era: focus on disease-modifying therapies and vaccination against COVID-19. NeurolTher. 10(2):539–555. https://doi.org/10.1007/s40120-021-00260-5

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Todorović, S., Vojinović, S., Savić, D. et al. Potential beneficial effect of IFN-β1a and ocrelizumab in people with MS during the COVID-19 pandemic. Acta Neurol Belg 124, 447–455 (2024). https://doi.org/10.1007/s13760-023-02421-9

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